Includes: 
- All SageMaker Studio Features
Enhancements: 
- No-Code/Low-Code Interface
- Visualization Options

Software and apps

Creative (multimedia and design)

Ideas

Technology demonstration and hardware

Nominations

Business plans

Analytics, visualizations, algorithms

Scientific

1st Pediatric Clinic of the University of Athens

23andMe (United States)

360DigiTMG

3Helix, Inc

7 Hill Gastroenterology

8LDesign

Aarhus University

Aarhus University Hospital

Abbott Diabetes Care

Abilene Christian University

Academia Sinica

Academic Medical Center

Academy of Science and Technology

Accudata Solution

Aclipse Therapeutics

Acri

Addenbrooke's Charitable Trust

Aditya Institute of Technology and Management

Advanced Research and Diagnostics Laboratory

Advanced Urogynecology of Michi

Adventhealth

AdventHealth Orlando

Aegerion Pharmaceuticals (United States)

Aegis School of Data Science and Cyber Security

Affiliated Hospital of Guizhou Medical University

Affinergy (United States)

African Institute for Mathematical Sciences

African Institute of Science and Technology

Ahvaz Jundishapur University of Medical Sciences

Aims Lab

Air Force Medical University

Air University

Aissms Institute of Information Technology

Ait Australian Institute of Technology Gmbh

Aizoon Technology Consulting

Ajou University

AK Children's Hospital

Akdeniz University

Akhtar Saeed Medical and Dental College

Akron Children's Hospital

Akron Nephrology Associates

Al-Ameen College of Pharmacy

Aland Central Hospital

Al Azhar University

Albany College of Pharmacy and Health Sciences

Albany Medical Center Hospital

Albany Research Institute

Albany Stratton Va Medical Center

Alberta Children's Hospital

Albert B. Chandler Hospital

Albert Einstein College of Medicine

Alder Hey Children's Hospital

Alere (United Kingdom)

Alexandria Faculty of Medicine

Alfred I. duPont Hospital for Children

Aligarh Muslim University

Alira Health

AliveDx

Allama Iqbal Open University

Allegheny Health Network

Allegheny Health Network ESOPHAGEAL INSTITUTE

All India Institute of Medical Sciences

All India Institute of Medical Sciences Bibinagar

All of Us Research Program

Allucent

Al-Mustaqbal University College

Alnylam Pharmaceuticals

Alpine Immune Sciences

Alpine Institute for Longevity Research and Diagnostics

Altair

Altai State University

Altran (France)

Altru Health System

Alzahra University

American Federation for Aging Research

American Registry of Pathology

American Society of Nephrology

American Speech Language Hearing Association

American University

American University In Cairo

American University of Beirut

American University of Beirut Medical Center

American University of Sharjah

Amgen (United States)

Amherst College

Amirkabir University of Technology

Am jain college

Amrita School of Arts and Science

Amrita Vishwa Vidyapeetham

Amsterdam University Medical Centers

Analytical Biological Services (United States)

Andhra University

Angion (United States)

Anhui Medical University

Animal Medical Center

A.N.I.T.S

Ankara University

Anna University, Chennai

Antaros Medical (Sweden)

Apellis Pharmaceuticals (United States)

National Library of Medicine

National Institute of Diabetes and Digestive and Kidney Diseases

NIDDK Liver Disease Section

NIDDK Phoenix - Gila River Indian Community

National Institute of Arthritis and Musculoskeletal and Skin Diseases

Eunice Kennedy Shriver National Institute of Child Health and Human Development

National Institute on Deafness and Other Communication Disorders

National Institutes of Health Clinical Center

National Institutes of Health

Division of Microbiology and Infectious Diseases

National Institute of Allergy and Infectious Diseases

Nih Division of Emergency Management

United States National Library of Medicine

National Institute On Aging

National Institute of Environmental Health Sciences

National Institute on Drug Abuse

National Institute of Dental and Craniofacial Research

Niddk/Kuh

Niddk/Dem

National Heart Lung and Blood Institute

National Institute of Neurological Disorders and Stroke

National Institute of Mental Health

National Institute on Minority Health and Health Disparities

National Human Genome Research Institute

Mitochondria Interest Group

National Center for Advancing Translational Sciences

National Cancer Institute

Foundation for the National Institutes of Health

Indian Institute of Technology Mandi

National Center for Biotechnology Information

National Institute on Alcohol Abuse and Alcoholism

NIDDK - Phoenix Epidemiology & Clinical Research Branch

Cash Prize

Non-monetary

Both cash prize & non-monetary

It has been proposed that the chronic, long-term ingestion of analgesics leads to specific renal pathology and renal failure. Previous studies suggested that the non–contrast-enhanced computerized tomography (CT) scan is a highly reliable tool for the diagnosis of analgesic-associated renal disease. The National Analgesic Nephropathy Study (NANS) is a case control study that was established to examine the association between heavy analgesic use and renal insufficiency and to investigate the ability of the CT scan to detect heavy analgesic use in the US population with end-stage renal disease (ESRD).

Patients with ESRD without a clear nonanalgesic cause for renal failure who had begun dialysis within the previous 3 months were enrolled in the study. A non-contract enhanced CT scan was performed using a standardized protocol. Three parameters—size, indentations, and calcifications—were used to identify patients who might have analgesic-induced kidney disease. Additionally, an interview was conducted to obtain information from patients concerning analgesic use, pre-dialysis signs and symptoms of renal disease, medical history, and demographics. 

The study concluded that findings of small indented calcified kidneys (SICK) did not occur with sufficient frequency in US patients with ESRD and heavy analgesic exposure to render the non-contrast-enhanced CT scan a sensitive tool to identify such individuals. Although the conclusion concerning the lack of diagnostic value of the CT scan is clear, the study did not address the overall relationship between analgesics and the progression of renal disease. Results showed an association between heavy analgesic ingestion and findings of SICK in incident US patients with ESRD, which seemed to be accounted for mostly by phenacetin-containing products; however, future studies are needed to learn whether there is an association in the US population between currently available analgesics and ESRD and whether the ingestion of NSAID or cyclooxygenase-2 inhibitors contribute to the development of ESRD.

The RAND Interstitial Cystitis Epidemiology Study (RICE) is an observational study that sought to develop a case definition for Bladder Pain Syndrome (BPS)/Interstitial Cystitis (IC) with known sensitivity and specificity and to estimate the prevalence of the condition, which at the time had never been done using a large-population model. BPS/IC, which is clinically diagnosed based on patient-reported symptoms, is a poorly understood condition that can cause significant disability.

 An expert panel developed a case definitions of BPS/IC based on a review of medical literature. This definition was tested on 599 adult women diagnosed with BPS/IC or other conditions characterized by pelvic symptoms. Testing revealed that no single epidemiological definition demonstrated both high sensitivity and high specificity, so two definitions were developed: one of high sensitivity/low specificity and one of low sensitivity/high specificity.
Using these two definitions, researchers then screened 96,995 US households to identify women who had bladder symptoms. Those with symptoms underwent a secondary, more intensive screening and were asked to provide more information regarding symptoms, medical history, medical treatments, impact on daily life, physical and mental health, and demographic information.  Multivariate modeling was used to construct population and non-response weights. Weighted data was used to calculate prevalence estimates for both definitions and estimate the number of women affected.

The Genetics of Kidneys in Diabetes (GoKinD) study was an initiative that aimed to identify genes that are involved in diabetic nephropathy. A large number of individuals with type 1 diabetes were screened to identify two subsets, one with clear-cut kidney disease and another with normal renal status despite long-term diabetes. Those who met additional entry criteria and consented to participate were enrolled. When possible, both parents also were enrolled to form family trios. DNA, serum, plasma, and urine samples and clinical information were collected from participants. A repository of genetic and clinical information was created for use in genetic analysis to investigate the genetic risk factors of the renal disease of Type 1 diabetes, with the ultimate aim of determining pathways for intervention to prevent diabetic kidney disease and allow targeting of preventive therapies.

GWAS data must be requested through dbGAP.

The TrialNet (TN20) study was a two-arm, multi-center, randomized, open-labeled clinical trial designed to assess the effects of varying doses and schedules of oral insulin on immunological and metabolic markers in relatives at risk for type 1 diabetes (T1D).

Participants were from the TrialNet Natural History/Pathway to Prevention (TN01) study, had a relative with T1D, and were positive for insulin autoantibodies and at least one other autoantibody. All participants received an active treatment of recombinant insulin in capsules of either 67.5 mg daily or 500 mg every other week. Participants visited the study site up to 11 times over one year for blood tests and other study procedures. During the beginning treatment phase, there were two visits one month apart for those given the 67.5 mg dose, and three visits two weeks apart to titrate the dose for those in the 500 mg treatment group. There were three additional treatment visits at months 2, 3, and 6, as well as four additional visits for follow-up at months 7, 8, 9, and 12. The primary outcome was the change in immune function as assessed by change in level or quality of T-lymphocyte or autoantibody biomarkers measured between 13 and 26 weeks compared to the baseline.

Children determined to be at an increased risk for development of type 1 diabetes (T1D), either due to known genetic markers or due to family history of T1D, are followed from birth and monitored on an annual basis for development of T1D-related autoimmunity. At annual clinic visits, participants are tested for development of these autoantibodies and data are collected related to environmental exposures. In addition to blood collection for determination of autoantibodies, serum and plasma are frozen and stored for future analyses, along with other biological samples such as throat swabs, rectal swabs, saliva, and urine. If T1D-related autoantibodies are detected, the participant is asked to increase the frequency of clinic visits to 2-4 visits per year in order to monitor for the onset of disease more closely. The endpoint of the study is diagnosis of T1D per the American Diabetes Association (ADA) criteria.

The ITCH study was a randomized, double-blind, placebo-controlled, parallel group, multi-center study in children with Alagille syndrome (ALGS). The study was designed to investigate the effects of LUM001 (Maralixibat), compared to placebo, on pruritus, serum bile acids, liver enzymes, and other biochemical markers associated with cholestatic liver disease, following daily dosing over a 13-week period.

The Hepatitis B Research Network Combination Entecavir and Peginterferon Therapy in HBeAg-Positive Immune-Tolerant Adults with Chronic Hepatitis B (HBRN Immune Tolerant A) study sought to determine the efficacy of treatment with 8 weeks of entecavir followed by 40 weeks of both entecavir and peginterferon in the treatment of chronic hepatitis B in hepatitis B “e” antigen (HBeAg) positive adults who were in the immune tolerant phase. Additionally, the study evaluated the safety and sustained responses after treatment with entecavir and peginterferon alfa-2a in the treatment of chronic hepatitis B in HBeAg positive adults in the immune tolerant phase.

Hepatitis B, a significant cause of cirrhosis and hepatocellular carcinoma worldwide, affects an estimated 800,000 to 1.4 million people in the United States. While progress has been made in the prevention, diagnosis, and treatment of chronic hepatitis B, challenges remain in identifying persons affected by the virus and in determining recommendations for management and treatment. The Hepatitis B Research Network (HBRN) was a multicenter network to investigate the etiology and progression of the disease, and to test the safety and efficacy of current treatment approaches. 

Hepatitis B virus (HBV) is largely a non-cytopathic virus. Therefore, liver disease pathogenesis and viral clearance in HBV infection is believed to be immune-mediated. At the same time, HBV persists with impaired antiviral immune effector responses that are potentially regulated by multiple immune pathways, including the CD28 costimulatory receptors and immune regulatory T cells. The Immune Regulation and Costimulation in Natural History of Chronic Hepatitis B (HBRN Immunology Cohort) study aimed to assess whether the balance between immune regulatory and effector responses in HBV-infected individuals defines the level of viremia, liver inflammation, and treatment outcomes.

Studies have shown that overweight and obese women are at increased risk for several complications of pregnancy, including gestational diabetes mellitus, hypertension, preeclampsia, and cesarean delivery. Additionally, the children of overweight or obese pregnant women show an increased risk of prematurity, congenital anomalies, and childhood obesity. The Lifestyle Interventions for Expectant Mothers (LIFE-Moms) consortium was a network of seven clinical centers and a data coordinating center to identify effective behavioral and lifestyle interventions that improve weight, glycemic control, and outcomes in obese and overweight pregnant women and their children. 

Participants were randomized between 9 weeks 0 days and 15 weeks 6 days gestation, and followed through one-year postpartum. Standardized measures were collected throughout gestation: at baseline (9-15 weeks), 24-27 weeks, 35-36 weeks, delivery, and one-year postpartum. Eligibility criteria, specific outcome measures, and assessment procedures were standardized across trials. Measures that were collected in all seven trials were defined as ‘core’ data and measures collected by four to six trials were defined as ‘super-shared’ data. All core and super-shared measures had a standardized definition and/or detailed procedures to facilitate uniform collection, a standardized training and certification process, and were entered into a common dataset at the data coordinating center.

Nonalcoholic fatty liver disease (NAFLD) affects 10%-30% of the general U.S. population and can progress to significant fibrosis and cirrhosis. When nonalcoholic steatohepatitis (NASH) is present, the 5-year and 10-year survivals are estimated at 67% and 59%, respectively. The presence of NASH and early fibrosis is currently established only by liver biopsy; noninvasively determining who has NASH and who is at risk for progressing to cirrhosis remains challenging.

The Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) was initiated by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) in 2002 to conduct multicenter, collaborative studies on the etiology, contributing factors, natural history, complications, and treatment of NASH. To meet these goals, patients with the full spectrum of NAFLD or cryptogenic cirrhosis were enrolled in an observational Database study.

Comprehensive data, including demographics, medical history, symptoms, medication use, diet and exercise habits, and routine laboratory studies were collected on all patients at entry and at annual visits for up to 4 years after enrollment. Study questionnaires administered at enrollment and at selected follow-up visits included AUDIT; Block Food Questionnaire; Skinner Lifetime Drinking History, Physical Activity Questionnaire, Modifiable Activity Questionnaire; and the MOS 36-Item Short-Form Health Survey. Specimens were collected at selected time points during follow-up. If liver biopsies were obtained as part of routine patient care, they were scored using the NASH CRN NAFLD Activity Score (NAS) and fibrosis score.

The intravascular administration of iodinated contrast media for diagnostic imaging is a common cause of acute kidney injury (AKI) and a leading cause of iatrogenic renal disease. Contrast-induced AKI is associated with serious adverse outcomes including death, need for dialysis, prolonged hospitalization, and acceleration in the rate of progression of underlying chronic kidney disease. The benefit of IV isotonic bicarbonate compared to IV isotonic saline and of N-acetylcysteine for the prevention of contrast-induced AKI and associated adverse outcomes remains unclear. The purpose of the PRESERVE trial was to compare the effectiveness of IV isotonic sodium bicarbonate with IV isotonic sodium chloride and oral NAC with placebo for the prevention of serious adverse outcomes in high-risk participants scheduled to undergo coronary or non-coronary angiography.

The Biomarker Collection and Analysis sub-study collected, banked, and analyzed the blood and urine of participants from the VA-funded PRESERVE trial. Blood and urine proteins and other markers may predict the development of contrast-induced acute kidney injury and diagnose the very early stages of this condition following angiography. In addition, these biomarkers may predict which patients that develop acute kidney injury following angiography are likely to experience serious longer-term complications such as death, need for dialysis, and/or progressive loss of kidney function.

Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis in the absence of a history of significant alcohol use or other known liver disease. Nonalcoholic steatohepatitis (NASH) is the progressive form of the disease, which results in cirrhosis, liver failure, and death in a substantial proportion of patients. Treatment approaches to NAFLD in adults and children target reduction in insulin resistance and oxidative stress. Several agents have been found to be promising as therapy of NAFLD in small clinical trials, but none have been proven to alter its natural history or outcome, and none are approved for general use in this disorder.  The Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) was established by the NIDDK in 2002 to investigate the natural history, pathogenesis, and therapy of NAFLD and NASH in both children and adults. The Farnesoid X Receptor (FXR) Ligand Obeticholic Acid in Nonalcoholic Steatohepatitis (NASH) Treatment (FLINT) trial was a multicenter, randomized, placebo-controlled clinical trial conducted by the NASH CRN to investigate the safety and efficacy of treatment of obeticholic acid compared to placebo in adults with nonalcoholic fatty liver disease.

Individuals with histologic evidence of NASH, based on a liver biopsy and a disease activity score (NAS) of at least 4 (with a score of at least 1 in each component of the NAS 8-point scale), were enrolled and randomized to treatment with either obeticholic acid (25 mg) or placebo for 72 weeks. Each participant received a baseline oral glucose tolerance test and a baseline MRI scan to determine liver fat content. Additionally, information was collected on demographics, alcohol consumption, and medication use. The primary outcome measure was improvement in the NAS score by at least 2 points with no worsening of liver fibrosis and was assessed by liver biopsy at 72 weeks. Secondary outcome measures included change in NASH diagnosis (from determinate or indeterminate to not-NASH), fibrosis score, hepatocellular ballooning score, hepatic fat fraction, serum aminotransferase and gamma-glutamyl transpeptidase (GGT) levels, fasting glucose levels, and health related quality of life scores.

A planned interim analysis of end-of-treatment liver biopsies from 58% (164/283) of enrolled patient demonstrated that the primary endpoint had been reached and the statistical significance crossed the preset boundry set for efficacy (p ≤ 0.0031). Accordingly, further liver biopsies were not performed. Additionally, because of the observation of disproportionate lipid abnormalities among patients receiving OCA and in the context of the study having met its primary endpoint, further treatment with OCA and placebo was discontinued and remaining patients completed a 24-week follow-up off treatment.

The second phase (MAPP II) of the NIDDK Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network was designed to conduct a prospective, observational study of men and women with urologic chronic pelvic pain syndrome (UCPPS). The MAPP II central protocol, the Trans-MAPP Symptom Patterns Study (SPS), phenotypically characterized UCPPS participants (and a limited number of healthy control participants) during an initial run-in period, at baseline, and during an extended follow-up period (up to 36 months) to further identify clinical and biologic factors associated with worsening and/or improvement of reported urinary and non-urinary symptoms and to further define clinically relevant UCPPS phenotypic subgroups. A central goal of MAPP II, like MAPP I, was to create a new knowledge base for informing future, targeted UCPPS clinical trials and ultimately to provide insights that will improve the clinical management of patients. 

Participants completed a series of in-clinic study visits at various time points, as well as online internet-based questionnaires in clinic and off site/at home, in which diverse patient-reported data was collected assessing urologic and non-urologic symptoms, health care utilization, flare status, and quality of life, among other domains. Physical exams and pelvic exams were also conducted at in-clinic visits. Biological samples were collected at various timepoints to allow studies of biomarkers, immunologic contributors, and the urologic microbiome.  The study also applied promising research methods in the pain field (e.g., functional/structural neuroimaging, quantitative sensory testing, and newly derived body pain maps) at baseline and longitudinally to allow for further systemic characterization of UCPPS in men and women.

MRI images for MAPP II participants are not included in the package, but are available upon request

The STOP-NAFLD (Losartan for the Treatment of Pediatric NAFLD) trial was a multicenter, double-masked, placebo-controlled, randomized phase 2 trial designed by the NASH Clinical Research Network to determine whether treatment with losartan improves measures of NAFLD in children. Children between the ages of 8 and 17 years with biopsy-proven NAFLD were eligible for the STOP-NAFLD study. Participants were enrolled and randomized to treatment with either 100 mg of losartan or matching placebo orally once daily for 24 weeks. Improvement in NAFLD at 24 weeks, defined as a decrease in serum alanine aminotransferase (ALT), was assessed as the primary outcome measure. Secondary outcome measures, also assessed at 24 weeks, included relative change in ALT; changes in serum aspartate aminotransferase (AST) and gamma-glutamyl transpeptidase (GGT); change in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR); changes in anthropometric measurements, BMI z-score, and serum lipid profiles; and self-reported quality of life.

The Clinical Trial of Entecavir/Pegylated Interferon in Immune Tolerant Children With Chronic HBV Infection (HBRN Immune Tolerant P) sought to determine the safety and efficacy of treatment using a combination of drugs (entecavir and pegylated interferon) in children ages 3-<18 years old with immunotolerant chronic hepatitis B. Children age 3-<18 years with immunotolerant chronic hepatitis B (CHB) infection who fulfilled the entry criteria received entecavir as monotherapy for 8 weeks and then combination therapy with entecavir and pegylated interferon by weekly subcutaneous injection until week 48. Children were to be followed for 48 weeks after discontinuation of therapy.

Pro non-inflammatory glomerular diseases, including minimal change disease (MCD), focal and segmental glomerulosclerosis (FSGS), and membranous nephropathy (MN), account for approximately 15% of prevalent end-stage renal disease (ESRD) cases in the United States. Development of successful therapeutic interventions is hindered by a limited knowledge of underlying glomerular disease mechanisms. In response to the need for research concerning these conditions, the Nephrotic Syndrome Study Network (NEPTUNE) was established to investigate the underlying disease mechanisms, elucidate pathogenesis, and identify therapeutic targets for clinical trials.
 
The NEPTUNE study is a prospective, observational study that enrolls children and adults with MCD, FSGS, and MN. At baseline, NEPTUNE collects information on demographics, clinical history, physical examination, as well as tissue samples from a renal biopsy visit, blood, and urine samples. Questionnaires are given to assess quality of life and self-reported health. Participants are assigned into a specific study cohort (MCD, FSGS, or MN) based on renal biopsy. After baseline assessment is complete, participants are followed over 30 months to collect data concerning health, quality of life, and outcomes, and urine and blood samples. NEPTUNE provides high-resolution clinical phenotypes of participants which are related to genome wide analyses to molecularly define disease categories, outcome predictors, and therapeutic targets. Molecular profiles and gene expression data are linked to phenotypic, genetic, and histologic data for systems biology analysis.

Hepatitis B, a significant cause of cirrhosis and hepatocellular carcinoma worldwide, affects an estimated 800,000 to 1.4 million people in the United States. While progress has been made in the prevention, diagnosis, and treatment of chronic hepatitis B, challenges remain in identifying persons affected by the virus and in determining recommendations for management and treatment. The Hepatitis B Research Network (HBRN) was a multicenter network to investigate the etiology and progression of the disease and to test the safety and efficacy of current treatment approaches. The HBRN Adult Cohort Study (HBRN Cohort A) was designed to describe participants with hepatitis B virus (HBV) infection and identify predictors of disease activation and progression. The relationship of HBV genotype to clinical, biochemical, and histological characteristics and to pregnancy was also explored.

Individuals of at least 18 years of age that were hepatitis B surface antigen (HBsAg) positive were enrolled in the HBRN Adult Cohort study. Baseline data were collected on demographics, medical history, family history of liver disease, and health behaviors. Participants were categorized into various phases of HBeAg-positive and HBeAg-negative HBV infection and stages of HBV disease for monitoring of changes in HBV infection status and quantitative HBsAg levels. The rate of various clinical outcomes—including hepatitis exacerbation marked by alanine aminotransferase (ALT) flare, antigen loss of HBsAg or HBeAg, cirrhosis, development of hepative decompensation, heptaocellular carcinoma (HCC), death, and liver transplantation—and the factors associated with these outcomes were assessed as primary outcome measures, evaluated at up to 288 weeks. Analyses were performed to determine whether a baseline HBsAg below 1,000 IU/mL and HBV DNA below 1,000 IU/mL were accurate predictors of people who were inactive carriers (defined as people who were HBsAg positive, HBeAg negative, had normal ALT and HBV DNA under 1,000 IU/mL on at least two occasions over a period of at least 6 months with HBV DNA under 1,000 IU/mL). Additionally, biospecimens were collected from participants to create a repository of resources for future studies.

The Combination Therapy of Peginterferon Alfa-2a and Tenofovir versus Tenofovir Monotherapy in HBeAg-positive and HBeAg-negative Chronic Hepatitis B (HBRN Immune Active) study sought to compare the long-term efficacy of combination therapy with peginterferon plus tenofovir versus tenofovir monotherapy in the treatment of chronic hepatitis B. This randomized (1:1) parallel group trial compared (i) tenofovir disoproxil fumarate (TDF) 300 mg daily for 192 weeks (4 years) and (ii) peginterferon (PegIFN) alfa-2a 180 µg weekly for 24 weeks plus TDF 300 mg daily for 192 weeks (4 years). Enrolled participants were stratified by HBeAg status (positive/negative), genotype (A versus all others), and cirrhosis (present versus absent). After 192 weeks of treatment, participants meeting criteria for treatment discontinuation stopped treatment and were followed for 48 weeks (total duration of treatment and follow up was 240 weeks). Emtricitabine/tenofovir coformulated as Truvada, approved for treatment of HIV but not for treatment of hepatitis B virus (HBV) infection, was offered to patients with primary nonresponse, partial virological response, or confirmed virologic breakthrough.

Since the introduction of highly active antiretroviral therapy (ART) in 1996, there has been a dramatic reduction in morbidity and mortality among those living with HIV. However, chronic liver disease due to co-infection with hepatitis B virus (HBV) or C (HCV) has emerged as the second leading cause of mortality among HIV-infected persons. The natural history of HBV infection is altered in those with HIV. Current guidelines recommend that most co-infected patients be treated for both HIV and HBV infection using combinations of ART that include tenofovir (TDF). Despite widespread adoption in the U.S., the effect of this regimen on long-term outcomes of HBV disease such as histologic severity, progression, risk of emergence of resistant HBV variants, and the long-term risks of TDF therapy remains unanswered.

The Hepatitis B Research Network (HBRN) was the first major effort to elucidate the natural history and treatment outcomes of persons with chronic HBV in the U.S. This HBRN ancillary study provided a unique opportunity to fill major gaps in HBV-HIV knowledge and to compare HBV-HIV infected persons to those with HBV monoinfection participating in the HBRN.

Hepatitis B, a significant cause of cirrhosis and hepatocellular carcinoma worldwide, affects an estimated 800,000 to 1.4 million people in the United States. Liver disease pathogenesis and viral clearance in hepatitis B virus (HBV) infection is believed to be immune-mediated, defined by distinct patterns of immune effector and regulatory responses. The Immune Regulation and Costimulation in Natural History and Therapeutic Outcome of Chronic Hepatitis B study was designed to examine the effects of antiviral therapy in host immune phenotype and to investigate if antiviral immune responses before, during, and after therapy can predict long term therapeutic response. This study is ancillary to two clinical trials conducted by the Hepatitis B Research Network, titled Combination Therapy of Pegylated Interferon Alfa-2a and Tenofovir Versus Tenofovir Monotherapy in Chronic Hepatitis B and Combination Entecavir and Peginterferon Therapy in HBeAg-Positive Immune-Tolerant Adults With Chronic Hepatitis B. It is hypothesized that therapeutic HBV suppression will enhance antiviral immune effector responses and reduce immune inhibitory factors in participants with chronic hepatitis B.

Participants for the Immune Regulation and Costimulation study are recruited from individuals who are enrolled in the HBRN clinical trials of adults with chronic hepatitis B. Immune regulatory and effector responses relative to serum HBV DNA, alanine aminotransferase (ALT), and clinical outcome are assessed as primary outcome measures. Specifically, IFN-gamma and IL 10 responses, T cell activation and costimulatory markers (PD1, CTLA4, CD28, CD127), FoxP3+ Treg frequency, dendritic cell frequency, and NK frequency are evaluated as measures of immune response. These measures are evaluated throughout the course of the two clinical trials until the termination of the treatment studies.

The Diabetes Prevention Program (DPP) is a clinical trial that investigated whether modest weight loss through dietary changes and increased physical activity or treatment with the oral diabetes drug metformin (Glucophage) could prevent or delay the onset of type 2 diabetes in high risk individuals with prediabetes.

The study enrolled overweight persons with elevated fasting and post-load plasma glucose concentrations. Participants were randomized to placebo, metformin (850 mg twice daily), or a lifestyle-modification program with the goals of at least a 7 percent weight loss and at least 150 minutes of physical activity per week. The primary outcome measure was development of diabetes, diagnosed on the basis of an annual oral glucose-tolerance test or a semiannual fasting plasma glucose test, according to the 1997 criteria of the American Diabetes Association: a value for plasma glucose of 126 mg per deciliter (7.0 mmol per liter) or higher in the fasting state, or 200 mg per deciliter (11.1 mmol per liter) or higher two hours after a 75-g oral glucose load. Participation in DPP continued after a diagnosis of diabetes was made, although study medication was discontinued and participants were sent to their local primary care provider for treatment of diabetes once fasting glucose was > 140 mg/dl.

Results showed that both lifestyle changes and treatment with metformin reduced the incidence of diabetes in persons at high risk compared with placebo. Furthermore, the lifestyle intervention was more effective than metformin in preventing the onset of diabetes.

Supplemental measurements were collected using biospecimens that were obtained during the original DPP clinical trial. These measurements included antibodies, biomarkers, hormones, and vitamin D levels to assess the relationships between sex hormones, diabetes risk factors, and the progression to diabetes. The supplemental data showed that sex hormones were associated with diabetes risk in men, but these associations were not found in women. Furthermore, obesity and glycemia were more important predictors of diabetes risk than sex hormones.

Nonalcoholic fatty liver disease (NAFLD) is a spectrum of liver conditions associated with fat accumulation that range from benign, non-progressive liver fat accumulation to severe liver injury, cirrhosis, and liver failure. NAFLD is highly prevalent within the United States and is most common in adults who are overweight or have diabetes, insulin resistance, or hyperlipidemia. However, the disease also occurs in children and in persons who are not obese or diabetic. The Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) was initiated by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) in 2002 to conduct multicenter, collaborative studies on the etiology, contributing factors, natural history, complications and treatment of NASH.

The NAFLD Pediatric Database 2 was a multicenter, prospective follow-up study of patients with NAFLD or nonalcoholic steatohepatitis (NASH) which aimed to investigate the etiology, pathogenesis, natural history, diagnosis, treatment, and prevention of NAFLD and NASH. The study included longitudinal follow-up of participants enrolled in earlier NASH CRN studies and recruited new participants. The study population included pediatric patients 2- 17 years old at the time of enrollment with histologically confirmed NAFLD or NASH located in the United States. Comprehensive data, including demographics, medical history, symptoms, medication use, alcohol use and routine laboratory studies was collected on all participants at entry and at follow-up visits every 48 weeks from enrollment. A standard of care liver biopsy was collected at baseline if not previously collected, and specimens were collected every 48 weeks during follow-up.

The PRIME study was a multicenter prospective phase I/IIA open label trial, aimed at assessing the feasibility, tolerability, and safety of intravenous immunoglobulin (IVIG) therapy following hepatic portoenterostomy (HPE) in infants with biliary atresia (BA). After enrollment, participants received three intravenous doses of IVIG at designated intervals over the first 60 days following HPE and were followed for 360 days. All infants in this trial were also treated with standardized doses of other routine standard-of-care treatments for BA and this routine clinical care was not modified by participation in this study.

The IMAGINE-II study was a multicenter, extension study of LUM001 in children diagnosed with Alagille syndrome (ALGS) who had completed participation in a core LUM001 treatment protocol (ITCH study). Efficacy was assessed by evaluating the effect of LUM001 on the biochemical markers and pruritus associated with ALGS.

Note: If requesting access to IMAGINE-II data, it is recommended to also request access to the ITCH Study data (<a href="https://repository.niddk.nih.gov/studies/itch/">https://repository.niddk.nih.gov/studies/itch/</a>) as IMAGINE-II is an extension study of ITCH.

Biliary atresia is a condition in which the common hepatic bile duct becomes blocked, preventing bile drainage from the liver. Biliary atresia occurs in infants and requires portoenterostomy, a surgical procedure, in order to re-establish bile flow from the liver to the small intestine. Despite the surgical intervention, about half of the children will need a liver transplant before the age of five. The aim of the START study was to determine whether corticosteroid treatment after portoenterostomy would improve bile drainage and reduce the need for liver transplantation, compared to surgery alone. 

The START study participants were recruited from the PROBE study and randomized into either the corticosteroid or placebo group within 72 hours after the portoenterostomy procedure. Participants were given their assigned treatments daily over the course of 13 weeks. After the treatment period, participants underwent follow-up testing and assessments until age 24 months.

Urinary tract infections (UTIs) are the most common serious bacterial infections in young children. When accompanied by a fever, there is an increased likelihood of a UTI also infecting the kidneys; between 15 and 52% of these children will develop kidney scarring as a result.

The Careful Urinary Tract Infection Evaluation (CUTIE) study was an observational study designed to determine why some children develop kidney scars after urinary tract infections (UTIs). The study was aimed at understanding which children were at the greatest risk of developing renal scarring following a UTI, so physicians can provide targeted therapies and appropriate interventions. Children between 2 months and 6 years of age who had a first or second UTI in the past 4 months were eligible for enrollment in the study. Participants were followed for 2 years through the course of five study visits, during which they were required to undergo a physical exam and provide information about recent medical history and quality of life via a questionnaire completed by parents. Additionally, blood and urine biospecimens were collected to monitor kidney function, and renal scans were performed to assess the development of kidney damage.
 
The CUTIE study was ancillary to the RIVUR (Randomized Intervention for Children with Vesicoureteral Reflux) study, which compared antibiotic prophylaxis to placebo in a cohort of children with a history of UTI and vesicoureteral reflux.  The CUTIE study focused specifically on children with a history of UTI who did not have vesicoureteral reflux. More information about the RIVUR study is available on the NIDDK repository website.

The Rare and Atypical DIAbetes NeTwork (RADIANT) is a multicenter prospective cohort study that is dedicated to characterizing (discovering and defining) rare and atypical forms of diabetes. Individuals will be screened for evaluation of suspected atypical diabetes of unknown origin. Among the pool of evaluated individuals, those found to have a known form of diabetes will be excluded from further study. The remaining participants will be prioritized for genetic/genomic analysis and further testing.

RADIANT has three distinct stages.

Stage 1:

Stage 1 participants will complete a consent form and a questionnaire to determine the potential for having atypical forms of diabetes. Participants identified as potentially having atypical forms of diabetes based on questionnaire responses will be asked to provide a blood sample to test for islet autoantibodies and complete additional questionnaires.

The RADIANT Adjudication Committee, which is comprised of a team of experts in diabetes, will assess the data collected in Stage 1 and select and prioritize participants to proceed to Stage 2 and 3 for Whole Genome Sequencing (WGS) and other testing.

Stage 2:

Stage 2 of the study includes genetic screening for known forms of monogenic diabetes. Participants will consent for this stage of the study, complete a family history questionnaire, and have blood collected for DNA and RNA extraction, storage, and analysis. Whole genome sequencing (WGS) will be performed on all DNA samples. If WGS does not identify a pathogenic/likely pathogenic variant in a known monogenic diabetes gene that is thought to explain the participant's diabetes, RNA Sequencing will be performed at Baylor College of Medicine.

Stage 3:

Stage 3 of the study includes deeper phenotyping. All participants who proceed to Stage 3 will visit a study clinic to consent and complete Stage 3 procedures which include: an Oral Glucose Tolerance Test (OGTT), additional blood collection, a detailed physical exam, and additional questionnaires.

Discovery Team Review:

The work of the Discovery Team is expected to be an iterative process analyzing all data collected up to this point in the study to understand the significance of novel variants. In some instances, the Discovery Team may determine that enrollment of the Proband's family members is necessary. Family members with suspected atypical diabetes will follow the same study procedures as described above. Affected and unaffected family members may also be enrolled for Sanger Sequencing or trio WGS. The Discovery Team may also recommend additional optional procedures to better characterize the participant's form of diabetes.

The Childhood Liver Disease Research Network (ChiLDReN) is a consortium committed to research into the etiology, pathogenesis, and treatment of rare pediatric liver diseases. Biliary atresia, one disorder studied by the consortium, is characterized by destruction or discontinuity of the extrahepatic biliary system, which results in obstruction to bile flow. Little is known about either the cause of biliary atresia or the factors that influence disease progression. The Biliary Atresia Study in Infants and Children (BASIC) is a prospective, observational study that was established by ChiLDReN to collect pertinent clinical information and biospecimens to aid in the understanding of the disorder. Specific aims of the study include identifying the gene(s) implicated in the etiology of biliary atresia, identifying the polymorphisms that may influence disease progression, and characterizing the natural history of the older, non-transplanted patients with biliary atresia.

Patients between the ages of 6 months and 20 years with a confirmed diagnosis of biliary atresia are eligible to participate in the study. Following enrollment, participants are separated into two cohorts: those who have their native liver and those who have received a liver transplant. Clinical information, including medical history, and biospecimens are collected at baseline. Those with their native liver will have clinical information collected annually up to 20 years of age. Genetic analyses are performed on the biospecimens provided to identify the gene(s) and polymorphisms implicated in the etiology and progression of biliary atresia.

The Prevention of Lower Urinary Symptoms (PLUS) Research Consortium sought to optimize prevention of lower urinary tract symptoms (LUTS) in women and adolescent females across their life spans. The ability to measure bladder health and key risk and protective factors was crucial to the PLUS mission. To describe and measure the spectrum of bladder health in diverse populations, researchers needed a valid and reliable instrument. Prior to the Validation of Bladder Health Instrument for Evaluation in Women (VIEW) study, the PLUS Consortium’s work on the design of a bladder health instrument was a culmination of expert opinion, information from focus groups, and incorporation of previously validated items and language where appropriate, along with cognitive interviews of participants from the general public. The VIEW study prospectively collected data to test and validate bladder health instrument (BHI) items for inclusion in a final bladder health scale (BHS) that assessed the full range of bladder health of women. The study collected data from the general population using mailed surveys, from the clinical population using surveys and in-person evaluations, and from postpartum women.

Noninvasive monitoring of liver fibrosis is an unmet critical need in cystic fibrosis (CF) liver disease. Liver biopsy is infrequently used in CF due to the patchy nature of liver involvement and is not suitable for longitudinal studies of progressive liver disease in CF. Indeed, unlike many other liver diseases, synthetic dysfunction is rare in CF liver disease. Portal hypertension due to hepatic fibrosis mediates most if not all of the complications seen in CF liver disease.

The Longitudinal Assessment of Transient Elastography in Cystic Fibrosis (ELASTIC-CF) study assessed if combining FibroScan® measurement of liver stiffness transient elastography with ultrasound would improve the prediction of the development of a nodular liver on ultrasound and development of portal hypertension over time in children and young adults with CF. Study visits occurred at baseline and for at least two annual follow-up visits. 

This study is an ancillary study to the CFLD PUSH study. If requesting access to the ELASTIC-CF data, it is recommended to also request access to the CFLD PUSH data to obtain comprehensive information collected on study participants.

The Chronic Renal Insufficiency Cohort (CRIC) Study is an observational study that examined risk factors for progression of chronic renal insufficiency (CRI) and cardiovascular disease (CVD) among CRI patients. The study enrolled adults aged 21 to 74 years with a broad spectrum of renal disease severity, half of whom were diagnosed with diabetes mellitus. Subjects underwent extensive clinical evaluation at baseline and at annual clinic visits and via telephone at 6 month intervals. Data on quality of life, dietary assessment, physical activity, health behaviors, depression, cognitive function, health care resource utilization, as well as blood and urine specimens were collected. Measures of kidney function and occurrence of new and worsening CVD  are the primary outcomes, among others.

Data from the recruitment and follow-up phases through Phase 3. Additionally, the data package includes variables related to APOL1, Echocardiogram, Electrocardiogram, and censored composite and individual outcomes. The data package includes data through 2024.

Retinal images for CRIC participants are not included in the package, but are available upon request.

The Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network was established to focus on a broader approach to the study of Interstitial Cystitis (IC)/Painful Bladder Syndrome (PBS) in men and women, and Chronic Prostatitis (CP)/Chronic Pelvic Pain Syndrome (CPPS) in men. These conditions are often grouped using the research definition Urologic Chronic Pelvic Pain Syndrome (UCPPS) in many MAPP Network studies.

Participants with some form or symptoms of UCPPS were asked to join the MAPP Network’s Phase I Trans-MAPP Epidemiology and Phenotyping (EP) Study. Participants with no UCPPS symptoms as well as participants with specific conditions (Fibromyalgia (FM), Irritable Bowel Syndrome (IBS), Chronic Fatigue Syndrome (CFS)) were recruited for the Trans-MAPP Control Study, as “Healthy Controls” and “Positive Controls,” respectively. These participants were reference groups for the Trans-MAPP EP Study.

The Pelvic Pain Twin Study was a small, pilot study conducted at one MAPP Network Discovery site during MAPP Phase I using a unique sample of female, community-based twins from the University of Washington Twin Registry. This effort represented a co-twin control study, with pairs that were discordant for IC/PBS and was designed to identify IC/PBS phenotypes, characterize pathological and physiological associations with IC/PBS, and describe the relationship between IC/PBS and related chronic overlapping pain conditions (COPCs). The study cohorts/targets included pairs of IC/PBS-discordant female twins and healthy-healthy twin pairs, and followed the clinical and biological characterization and biological specimen collection strategy outlined in the MAPP Phase I Trans-MAPP EP Study protocol.

The SIGT study sought to develop a low-cost screening test for identifying people with prediabetes and diabetes in the general population. The gold standard test to determine glucose tolerance, the oral glucose tolerance test (OGTT), is time-intensive and inconvenient for patients. The study hypothesized that using a simpler test, an oral glucose challenge test (GCT), could constitute an effective and low-cost method of screening for diabetes in adults. The GCT is currently used in screening for gestational diabetes, which is pathophysiologically similar to early glucose intolerance (high glucose levels after a challenge).

Participants without a prior diagnosis of diabetes were enrolled and performed two outpatient visits. At the first visit, participants underwent a GCT, which involved drinking 50 grams of oral glucose within 5 minutes and measurement of plasma and capillary glucose after 1 hour. At the second visit, participants received an OGTT following an overnight fast, with samples at baseline, 1 hour, and 2 hours. Investigators used the test results to compare the performance of the GCT to the OGTT for determining glucose tolerance (i.e., prediabetes or diabetes).

The LABS-3 Psychosocial Issues and Bariatric Surgery study conducted an in-depth examination of the psychosocial aspects of surgery among a geographically, ethnically, and racially diverse sample of men and women undergoing bariatric surgery. The study had experts in the areas of psychopathology, eating behaviors, and quality of life to conduct a naturalistic study using state-of-the-art assessment tools, and documented the relationships among psychosocial factors over a three-year period to examine psychosocial predictors of surgical outcomes.

The Analysis of Prediction by Ultrasound of the Risk of Hepatic Cirrhosis in Cystic Fibrosis Cohort Using Advanced MRI to Characterize and Predict CF Liver Disease (PUSH-MRE) study was a prospective cross sectional ancillary study of children and adolescents with cystic fibrosis enrolled in the Prediction by Ultrasound of the Risk of Hepatic Cirrhosis in Cystic Fibrosis Liver Disease (CFLD PUSH) study. PUSH-MRE sought to determine the feasibility of MRI and magnetic resonance elastography (MRE) to predict the development of advanced liver disease in children and adolescents with CF. Participants were a subset to those enrolled in the CFLD PUSH study, at 8 of the 11 centers that had research MRE capability. 
This study is an ancillary study to the CFLD PUSH study. If requesting access to the PUSH-MRE data, it is recommended to also request access to the CFLD PUSH data to obtain comprehensive information collected on study participants.

The epidemic of type 2 diabetes (T2D) in the United States incurs significant human and economic costs, including severe long-term complications such as retinopathy, nephropathy, neuropathy, and cardiovascular disease (CVD). Although research has led to the creation of new classes of glucose-lowering medications, selecting the most effective way to achieve proper glycemic control among the variety of treatment options presents a considerable challenge for healthcare providers. The Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE) was a practical, unmasked clinical trial that evaluated the effectiveness of commonly prescribed diabetes medications—when used alongside metformin—on lowering glycemia and enhancing patient-centered outcomes. 

Individuals with duration of T2D of less than 10 years and an age of at least 30 years at time of diagnosis were eligible for the study. Participants completed a run-in phase to adjust metformin to a dose of at least 1,000 mg/day and a target dose of 2,000 mg/day. Following the run-in period, participants with baseline hemoglobin A1c values of 6.8-8.5% (51-69 mmol/mol) were randomized to treatment with metformin and one of four medications: sulfonylureas, dipeptidyl peptidase 4 inhibitors, glucagon-like receptor agonists, and insulin. All participants continued follow-up for a period of 4-7 years (depending on the time of entry), including those who reached the primary outcome.

Continuous Glucose Monitoring (CGM) data are not included in the package, but are available upon request.

Acute pancreatitis is among the most common gastrointestinal causes for hospitalization in the U.S. Roughly one in five patients with acute pancreatitis will have recurrent bouts. Recurrent acute pancreatitis (RAP) is a strong risk factor for progression to chronic pancreatitis, an irreversible fibroinflammatory disease that greatly impacts quality of life, and is also a risk factor for pancreatic cancer. Increased intraductal pressure is an accepted cause for precipitating an episode of acute pancreatitis. Pancreas divisum, seen in 7-10% of the general population, occurs when the dorsal and ventral pancreatic ducts have incomplete or nonexistent fusion during early embryologic development. Using this rationale, endoscopists often perform endoscopic retrograde cholangiopancreatography (ERCP) with minor papilla sphincterotomy (miES) in patients who have idiopathic RAP (iRAP) and pancreas divisum with a goal to reduce subsequent attacks. This practice remains highly controversial, due to major limitations in the available data which are derived almost exclusively from small, retrospective cohort studies with inconsistent and subjective outcomes. This is one of the highest risk indications for ERCP, having post-ERCP pancreatitis rates of 10-20%.

The SpHincterotomy for Acute Recurrent Pancreatitis (SHARP) trial was a sham-controlled, single blind with a blinded outcome assessment, randomized trial evaluating the impact of miES on the natural history of iRAP in patients with pancreas divisum. Eligible participants were randomized using an equal (1:1) allocation to either endoscopic ultrasound (EUS) + sham or EUS + ERCP with miES and followed for up to 48 months. A biorepository was established for future exploratory studies of novel risk factors for RAP, progression to chronic pancreatitis and its sequelae, and factors associated with response to miES. Patients fulfilling the entry criteria but declining enrollment into the randomized trial were approached to enroll into an observational cohort.

The purpose of the SVI study was to determine whether rectal indomethacin had no important loss of efficacy compared to the combination of rectal indomethacin and prophylactic pancreatic stent placement in patients undergoing high-risk endoscopic retrograde cholangiopancreatography (ERCP) who required pancreatic stent placement (PSP) for the sole purpose of pancreatitis prevention. The primary efficacy endpoint was defined as post-ERCP pancreatitis defined per consensus (Atlanta) criteria. 

This was a blinded, two-armed, non-inferiority trial where eligible patients were randomized to either the combination treatment or indomethacin alone. Participants were randomized during the ERCP procedure after eligibility was confirmed and received indomethacin at the time of randomization. The primary efficacy endpoint of post-ERCP pancreatitis within 2 days from randomization was assessed by an independent adjudication panel. The participant follow-up period was 30 days from randomization.

Gastroparesis, a syndrome in which patients experience delayed gastric emptying, is characterized by symptoms such as nausea, vomiting, bloating, abdominal pain, and early satiety. Despite the significant morbidity of the condition, research and characterization of the clinical features of gastroparesis are limited, hindered by challenges such as single centers and small study populations. The Gastroparesis Registry (GpR) was an observational study created by the Gastroparesis Clinical Research Consortium (GpCRC) to enroll a sufficiently large number of patients to elucidate the clinical features of the condition and investigate their association with various patient characteristics. Following conclusion of the GpR study, the Gastroparesis Registry 2 (GpR 2) was initiated as follow-up to expand the registry for continued investigation of the epidemiology, etiology, and clinical course of gastroparesis.

Individuals with symptoms of gastroparesis of at least 12 weeks duration and delayed gastric emptying on scintigraphy were enrolled. Individuals with symptoms of gastroparesis but with normal gastric emptying were also enrolled as a reference group. Participants must have had an upper endoscopy within 2 years prior to registration to rule out other disorders. During screening, data were collected on medical history, physical examination, 4-hour gastric emptying scintigraphy results, and symptoms of gastroparesis and psychological functioning using participant-completed questionnaires. Additionally, diagnostic tests of wireless motility capsule to assess whole gut transit, autonomic function testing, and electrogastrography were done to investigate the pathophysiology of the condition. Participants were followed via site visits every 24 weeks and information was collected on symptoms, quality of life, treatments being used, and change in medical condition. Plasma and serum specimens from each participant were collected and stored.

Most studies of participants with stent-associated symptoms have either focused on stent factors, including differing stent materials, lengths, configurations, and drug-eluting stents, or investigated medications that target lower urinary tract symptoms. Despite these investigations, little progress has been made toward substantially mitigating stent-associated symptoms, or developing greater insights into mechanisms and/or predictive factors of more severe stent-associated symptoms. The Study to Enhance Understanding of Stent-associated Symptoms (STENTS) was a prospective observational cohort study of individuals undergoing clinically-indicated unilateral ureteroscopy with planned ureteral stent placement for treatment of a ureteral or renal stone. The observational cohort study also included a nested qualitative cohort. Participants completed a psychosocial profile and periodic symptom assessments, and urine specimens in addition to demographic, clinical, and operative characteristics. For adult participants, sensory testing and plasma specimens were also performed.

BESST was a multi-center, randomized, double-masked, placebo-controlled, parallel treatment groups phase 2 trial to determine whether buspirone, a 5-HT 1a receptor agonist, improved early satiety and postprandial fullness in participants with symptoms of gastroparesis and with at least moderately severe symptoms of early satiety and/or postprandial fullness. After enrollment, participants were treated with buspirone (10 mg three times per day) or a matching placebo for 4 weeks, followed by a 2-week post-treatment washout period. The primary outcome for the study was the 4-week change (week 4 minus baseline) in the 4-item postprandial fullness/early satiety subscore (higher scores indicate worse symptoms) from the Patient Assessment of Gastrointestinal Disorders Symptom Severity Index (PAGI-SYM) questionnaire. The study hypothesized that 10 mg t.i.d. buspirone treatment would reduce mean postprandial fullness/early satiety symptom severity subscores over 4-weeks compared to treatment with placebo.

The Safety and Cardiovascular Efficacy of Spironolactone in Dialysis-Dependent End-Stage Renal Disease (SPin-D) Trial was a randomized, blinded, placebo-controlled 4-arm trial that compared placebo with three doses of spironolactone for patients with end-stage renal disease (ESRD) receiving treatment with hemodialysis. Participants were randomized in a 2:1:1:1 fashion to placebo or spironolactone, with equal proportions randomized to each of three spironolactone doses: 12.5, 25, or 50 mg once daily. The study was conducted in two phases ‒ a dose escalation phase and a treatment phase. 

All participants randomized to spironolactone initiated treatment at 12.5 mg daily. Participants were evaluated weekly for tolerability, hypotension, and hyperkalemia. At 2 weeks, if the initial dose had been tolerated, participants randomized to the 25 or 50 mg spironolactone arm increased the dose to 25 mg for 2 weeks with weekly evaluation for tolerability, hypotension, and hyperkalemia. Participants randomized to 12.5 mg spironolactone or placebo arm continued on the same dose with weekly evaluation for tolerability, hypotension, and hyperkalemia. At 4 weeks, participants randomized to the 50 mg spironolactone arm increased the dose to 50 mg if the 25 mg dose was tolerated with weekly evaluations for tolerability, hypotension, and hyperkalemia until 6 weeks. Participants randomized to 12.5 mg, 25 mg, or placebo continued on the same dose with weekly evaluation for tolerability, hypotension, and hyperkalemia until 6 weeks. In order to maintain the blind, during the dose escalation phase, all study participants regardless of randomized assignment, received new study drug kits every 2 weeks and were evaluated weekly. At the end of the dose escalation phase, participants continued treatment based on the randomized dose assignment for an additional 30 weeks (treatment phase) such that the total duration of study medication was 36 weeks. The dose of spironolactone or placebo was decreased during the dose-escalation and follow-up phases for hypotension, hyperkalemia, or other dose limiting side effects.

Nonalcoholic fatty liver disease (NAFLD) is a spectrum of liver conditions that can progress to significant fibrosis and cirrhosis. There are an estimated 40-90 million individuals within the United States with NAFLD, 10- 30% of whom have NASH and may develop NASH-related cirrhosis. Identifying through non- invasive means those individuals who are at risk for progressive liver disease remains challenging.

The Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) was initiated by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) in 2002 to conduct multicenter, collaborative studies on the etiology, contributing factors, natural history, complications and treatment of NASH. 

The NAFLD Adult Database 2 continued the longitudinal follow-up of participants enrolled in earlier NASH CRN studies and recruited new participants with recent liver biopsies. Comprehensive data, including demographics, medical history, symptoms, medication use, alcohol use and routine laboratory studies were collected on all participants at entry and at annual visits for up to 10 years after enrollment. A liver biopsy was collected at baseline if not collected in a prior NASH CRN study. Study questionnaires administered at enrollment included Skinner Lifetime Drinking history, Alcohol Use Disorders Identification Test (AUDIT) and Beverage Questionnaire (BEVQ-15). 

Specimens were collected every 48 weeks during follow-up. If liver biopsies were obtained as part of routine patient care, they were scored using the NASH CRN NAFLD Activity Score (NAS) and fibrosis score. The Interim drinking history (AUDIT-C) and BEVQ-15 were collected at follow-up visits.

The RISE FOR HEALTH study (RISE) was an initiative of the Prevention of Lower Urinary Tract Symptoms (PLUS) Research Consortium to improve bladder health in women and girls. The RISE study examined the risk and protective factors for bladder health and lower urinary tract symptoms (LUTS) in a cohort of well-characterized women, and assessed the distributions of bladder health and bladder health knowledge, attitudes, and beliefs in women from across the nation. Importantly, RISE explored the influence of novel factors, such as the toileting environment, behaviors, and positions, on bladder health, using new measures developed by the PLUS Research Consortium. The study benefited from transdisciplinary contributions from community engagement and cross-cultural experts to ensure that RISE was responsive to the needs of community members and used measures that were reviewed for acceptability and comprehension in diverse women, including Spanish language speakers. Together, these features helped RISE to the foundation for knowledge about antecedent risk and protective factors for bladder health and LUTS, and inform future studies designed to promote bladder health and prevent LUTS in women.

The Helping to End Addiction Long-term (HEAL) Initiative conducted the Hemodialysis Pain Reduction Effort (HOPE) Consortium Trial to Reduce Pain and Opioid Use in Hemodialysis study which was a multicenter randomized clinical trial that evaluated approaches to reducing pain and opioid use among patients with chronic pain who were receiving maintenance hemodialysis for end-stage kidney disease. The trial hypothesis was that pain coping skills training, a cognitive behavioral therapy intervention, would be effective at reducing pain interference, opioid use, and other pain-related outcomes, and that buprenorphine would be acceptable and tolerable as an approach to managing physical dependence on opioids in this patient population. Participants were recruited from participating dialysis clinics at enrolling sites. Eligible participants were randomized to Pain Coping Skills Training (PCST) or Usual Care for 24 weeks, followed by an exploratory, nonrandomized evaluation of buprenorphine as an alternative to full-agonist opioid medications for the subset of participants receiving opioid medication at 20 morphine milligram equivalents per day or higher at Week 24. PCST consisted of 12 weeks of weekly coach-led sessions delivered by videoconferencing and an additional 12 weeks of daily interactive voice response sessions by telephone. Participants were followed in the study for 36 weeks after randomization.

The Prospective Evaluation of Chronic Pancreatitis for Epidemiologic and Translational Studies (PROCEED) is an observational cohort study of adult participants with suspected or definite chronic pancreatitis (CP) that are prospectively ascertained and undergo yearly follow-up during clinical care. Participants complete study questionnaires, provide specimens, and consent for access to their protected health records at baseline and during follow-up for the duration of the study. Long term follow-up is needed to assess for progression to CP-related endpoints, pancreatic cancer, and overall survival. Participants of varying health status but without symptoms or diagnosis of pancreatic disease, or those with unexplained upper abdominal pain but no evidence of pancreatic disease, are classified as controls. Subsets of participants undergo laboratory tests, radiologic, or diagnostic endoscopic procedures for clinical or research purposes.

Type 1 diabetes develops when fully activated T-cells attack beta cells in the pancreas, causing insulin production to shut down. In order for a T-cell to be fully active, a co-stimulatory signal is required. Abatacept (CTLA-4-lg) prevents full T-cell activation by modulating co-stimulation. During the earlier stages of beta cell destruction, individuals progress from normal glucose tolerance to abnormal glucose tolerance, a precursor to type 1 diabetes. Intervention in participants with normal glucose tolerance may be more effective than in those with abnormal tolerance.

The purpose of the TrialNet 18 (TN18) study was to determine whether Abatacept treatment prevented or delayed the development of abnormal glucose tolerance and type 1 diabetes mellitus in at-risk relatives of participants with type 1 diabetes. Since C-peptide production is directly related to insulin production, this study also used oral glucose tolerance testing to evaluate the effect of Abatacept on C-peptide response. Participants were randomized into either the Abatacept or placebo group. The groups received an intravenous infusion of their respective treatments at specific points during the course of the study. Participants were regularly monitored and assessed for the development of abnormal glucose tolerance or diabetes.

The ICCRN RCT2 study was a randomized, double-blind, placebo-controlled clinical trial that investigated the safety and effectiveness of the immunosuppressant CellCept (Mycophenolate Mofetil) in treating refractory interstitial cystitis (IC). Interstitial Cystitis (IC) is a bladder syndrome characterized as painful, debilitating and chronic, with no widely effective treatment. Characteristic symptoms include pain with bladder filling, and marked urinary frequency (to relieve pain). The presentation of symptoms can be quite variable among patients, suggesting that IC is a multi-factorial syndrome with several proposed etiologies, some of which may be interrelated. If the etiology of IC/PBS is in part due to an induced autoimmune/inflammatory disorder, immunosuppressant therapy is a reasonable consideration for a treatment trial.
 
Eligible participants were randomized to either CellCept or matching placebo in a 2:1 ratio. All subjects were treated and followed for a period of up to 16 weeks after randomization, including 12 weeks of study treatment and 4 weeks post-treatment. Participants completed the Global Response Assessment (GRA) following treatment. Laboratory values (complete blood counts, liver enzymes) and physical symptoms were closely monitored for adverse events at regular intervals throughout the study. The study was halted prematurely as a result of a combination of factors including a black box warning issued by the Food and Drug Administration, slow recruitment and a decreased efficacy of the drug compared to placebo (interim efficacy analysis requested by the Data and Safety Monitoring Board) 
The results of this limited study did not confirm or refute the hypothesis that immunosuppressive therapy may be beneficial to at least a subgroup of patients with IC.

The TN22 study tested a medication, hydroxychloroquine (HCQ), to assess safety and effectiveness to prevent individuals at risk of type 1 diabetes (T1D) from progressing to type 1 diabetes. HCQ is approved by the U.S. Food and Drug Administration as a treatment for malaria, lupus, and rheumatoid arthritis. HCQ has been used extensively for treatment of autoimmune disease in adults, children, and during pregnancy. This medication had not been previously studied as a treatment to prevent T1D. The study was a 2-arm, double-blinded, multicenter, 2:1 randomized, placebo-controlled clinical trial. Participants received hydroxychloroquine or placebo and close monitoring for progression of T1D.

The Vitamin D and Type 2 Diabetes (D2d) study was a multicenter, randomized (1:1), double-masked, placebo-controlled, parallel-group, primary prevention clinical trial with two arms (4000 IU oral daily vitamin D3 versus placebo) of participants at high risk for diabetes (with pre-diabetes) that were followed for a median of 2.5 years.


Following the LABS-1 study, the LABS-2 study was initiated to examine the longer-term safety, outcomes, and durability of health changes of bariatric surgery. The primary objectives of the LABS-2 study were to determine weight, medical, surgical, and behavioral outcomes, including incidence and remission of co-morbid conditions, and to evaluate participant, procedure, and other characteristics that were associated with these outcomes. The study included participants who underwent bariatric surgery at LABS clinical centers through 2009. Clinical assessments, detailed interviews, and questionnaires were administered at several post-operative time points (30 days, 6 months, 12 months following surgery, and annually thereafter) to assess risks of surgery and changes in clinical, metabolic, and psychosocial characteristics in participants following bariatric surgery. Detailed data about the surgical procedure and peri- and post-operative care were also collected to determine if components of the surgical procedure, care, and/or clinical/demographic participant characteristics were associated with post-operative risks and changes in status.

An ancillary study from LABS-2 regarding psychosocial issues in bariatric surgery conducted psychological assessments of eating disorder symptomology and general psychopathology at three timepoints: approximately 2-3 weeks pre-operative, 2 months post-operative, and 8 months post-operative. Another ancillary study from LABS-2 regarding energy expenditure assessed whether activity thermogenesis increased in participants undergoing bariatric surgery post-operatively at 6 and 24 months compared to pre-operatively. Both ancillary studies are available in the data package for LABS-2 along with the full data.

The Diabetes Control and Complications Trial (DCCT) was a multicenter, randomized clinical trial designed to compare intensive with conventional diabetes therapy with regard to their effects on the development and progression of the early vascular and neurologic complications of type 1 insulin-dependent diabetes mellitus. The DCCT study involved participants, ages 13 to 39, with type 1 diabetes and either no or minimal background retinopathy. Participants were required to have had diabetes for at least 1 year but no longer than 15 years.

Once enrolled, participants were randomized to receive standard therapy, consisting of not more than two injections of insulin per day, or intensive therapy, consisting of either subcutaneous insulin infusion by pump or at least three subcutaneous injections of insulin daily, targeting near-normal glycemia. Both groups received the same dietary management and education program. Blood glucose and hemoglobin A1c measurements were used as primary indicators of metabolic control.

Cystic fibrosis is an inherited condition in which cell secretions are thick and sticky, instead of thin and slippery. The secretions obstruct passageways and ducts, leading to severe internal damage. Patients with cystic fibrosis sometimes develop advanced liver disease (CFLD). Hepatic cirrhosis can occur with CFLD, as a result of the inflammation and scarring caused by clogged bile ducts.

The Prediction by Ultrasound of the Risk of Hepatic Cirrhosis in Cystic Fibrosis Liver Disease (CFLD PUSH) study was a prospective longitudinal study that aimed to determine the utility of abdominal ultrasound to predict the development of cirrhosis in patients with cystic fibrosis as indicated by a nodular liver on ultrasound. Participants underwent abdominal ultrasound at enrollment and based on the outcome, were placed in one of four groups. Within a 10-year period, participants underwent other specimen collection procedures in addition to abdominal ultrasound. This study also monitored the effects of cystic fibrosis on associated pulmonary and nutritional issues.

Urge incontinence, the involuntary urine loss associated with a strong desire to void, is one of several types of urinary incontinence (UI) and has one of the greatest impacts on quality of life. Common treatments for urge incontinence include behavioral training and antimuscarinic medications, but long-term adherence with medication therapy can be difficult to achieve. The Behavior Enhances Drug Reduction of Incontinence (BE-DRI) study was a multicenter, randomized clinical trial that combined behavioral training and pharmacological treatment with the goal of improving patient outcomes. The primary aim of this randomized clinical trial was to determine whether combining antimuscarinic drug therapy with supervised behavioral training, compared to drug therapy alone, improves the ability of women with urge incontinence to achieve clinically important reductions in incontinence episodes and to sustain these improvements after discontinuing medication. 

Participants with urge incontinence (defined as urge symptom index > stress symptom index on the Medical, Epidemiological, and Social Aspects of Aging Questionnaire) were enrolled in the study and randomly assigned either to drug therapy alone or combined behavioral and drug therapy. Drug therapy was tolterodine tartrate at a dose of 4 mg per day. Combination therapy included drug and behavioral training, which consisted of teaching pelvic floor muscle control and exercises, delayed voiding to increase voiding interval, individualized fluid management, and strategies to diminish urgency, suppress bladder contractions, and prevent both stress and urge incontinence. Treatment was discontinued for both groups after 10 weeks. The primary outcome measure, assessed at 8 months, was no receipt of drugs or other therapy for urge incontinence and a 70% or greater reduction in frequency of incontinence episodes. Secondary outcome measures included reduction in incontinence, self-reported satisfaction and improvement, and scores on validated questionnaires measuring symptom distress and health-related quality of life.

Results showed that the rate of successful discontinuation of therapy at 8 months was the same in the combination therapy and drug therapy alone groups, although a higher proportion of participants who received combination therapy than drug therapy alone achieved a 70% or greater reduction in incontinence at 10 weeks. The study concluded that the addition of behavioral training to drug therapy may reduce incontinence frequency during active treatment but does not improve the ability to discontinue drug therapy and maintain improvement in urinary incontinence.

The Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL) was a consortium of 9 U.S. liver transplant centers performing adult-to-adult living donor liver transplant (AALDLT) with the primary goal of examining outcomes of AALDLT versus deceased donor liver transplant (DDLT).  AALDLT is a relatively new procedure increasingly used at major transplantation centers. Relatively small numbers of cases are performed at any one center and approaches to the patient and donor are too diverse across centers to provide reliable and generalizable information on donor and recipient outcomes from individual centers. Therefore, the consortium was organized to accrue and follow sufficient numbers of patients being considered for and undergoing AALDLT to provide generalizable results from adequately powered studies.

The Adult to Adult Living Donor Liver Transplantation Cohort Study (A2ALL) consisted of both retrospective and prospective studies of AALDLT. Legacy data from the A2ALL retrospective cohort is housed in the NIDDK Data Repository. The A2ALL retrospective cohort comprised 819 adult patients, each with a potential living donor, evaluated between January 1, 1998 and February 28, 2003. The retrospective study was designed to gain initial insights into outcomes associated with liver transplant procedures, with data drawn from existing medical records and patient materials. It was hypothesized that pursuit of a living liver allograft leads to decreased pre-transplant morbidity and mortality and better long term outcomes for patients starting from the point at which listed patients have a potential donor evaluated (at least a history and physical examination). The study analyzed numerous variables to determine the factors influencing allograft survival in recipients.
 
The A2ALL study showed evidence that AALDLT is a viable option for liver replacement with outcomes that improve with center experience. Donor characteristics associated with survival included younger age and cold ischemia time of the right lobe graft. 

MRI and CT Scan images from subjects enrolled in A2ALL are not included in the data package, but are available upon request.

Chronic kidney disease (CKD) is a life-long condition that often results in substantial morbidity and premature death due to complications from a progressive decrease in kidney function. The early detection of, and initiation of therapy for, CKD is key to delaying or preventing progression to end-stage renal disease (ESRD). The CKiD (Chronic Kidney Disease in Children, <a href="https://statepi.jhsph.edu/ckid/">https://statepi.jhsph.edu/ckid/</a> <a class="ExternalLinkIcon_externalLink__tu8Oz" href="https://www.niddk.nih.gov/disclaimers" target="_blank" rel="noopener noreferrer"> <svg aria-label="This link is external" xmlns="http://www.w3.org/2000/svg" width="10" height="10" fill="currentColor" class="bi bi-box-arrow-up-right" viewBox="0 0 16 16">
        <path fill-rule="evenodd" d="M8.636 3.5a.5.5 0 0 0-.5-.5H1.5A1.5 1.5 0 0 0 0 4.5v10A1.5 1.5 0 0 0 1.5 16h10a1.5 1.5 0 0 0 1.5-1.5V7.864a.5.5 0 0 0-1 0V14.5a.5.5 0 0 1-.5.5h-10a.5.5 0 0 1-.5-.5v-10a.5.5 0 0 1 .5-.5h6.636a.5.5 0 0 0 .5-.5z"></path>
        <path fill-rule="evenodd" d="M16 .5a.5.5 0 0 0-.5-.5h-5a.5.5 0 0 0 0 1h3.793L6.146 9.146a.5.5 0 1 0 .708.708L15 1.707V5.5a.5.5 0 0 0 1 0v-5z"></path>
    </svg></a>) study is a prospective cohort study of children with CKD that investigates risk factors and outcomes of the disease.

The study population consists of three cohorts. Cohort 1 includes 586 racially and ethnically diverse children recruited between the ages of 1 and 16 years with mild to moderately impaired kidney function (defined by an estimated GFR between 30-90 ml/min/1.73m2). Cohort 2 includes 305 children with mildly impaired kidney function (defined as an estimated GFR between 45-90 ml/min/1.73m2). Cohort 3 includes 209 children with non-glomerular diagnosis and duration of kidney disease less than 5 years. At baseline, participants underwent a physical examination, in addition to assessments of kidney, cardiovascular, and neurocognitive symptoms and function. Similar measures of kidney function, neurocognitive function, markers of risk factors for cardiovascular disease, growth and other co-morbid conditions are assessed at regularly scheduled study visits. Biospecimens, including serum, plasma, and urine are also collected. The primary outcome measure is the rate of decline of GFR, which is measured repeatedly over time in cohort participants. A secondary outcome measure is the time to ESRD, defined by transplantation, dialysis, or a 50% decrease in GFR.

Baseline and follow-up biospecimens and data through April 30, 2022 are available from the Repository.

Acute kidney injury is a common complication of acute illness, affecting approximately 2 to 7% of hospitalized patients and more than 35% of critically ill patients. While renal-replacement therapy is the main treatment method for patients with acute kidney injury, the optimal timing for the initiation, method, and dosing of therapy is uncertain. Given this uncertainty, the Acute Renal Failure Trial Network (ATN) study was established to determine whether more intensive renal replacement therapy decreases mortality among critically ill patients with acute kidney injury. 

The study was a multicenter, prospective, randomized trial of two strategies for renal-replacement therapy in patients with acute kidney injury. Participants were randomized to receive intensive (i.e., intermittent hemodialysis and sustained low-efficiency dialysis six times per week and continuous venovenous hemodiafiltration at 35 ml/kg of body weight/hour) or less intensive renal-replacement therapy (i.e., the corresponding treatments were provided three times per week and at 20 ml/kg/hour). The assigned renal-replacement therapy was provided for up to 28 days after randomization or until recovery of kidney function, discharge from acute care, withdrawal of life-sustaining therapy, or death. The primary outcome measure was death from any cause by day 60. Recovery of kidney function (defined as lack of need for continuing dialysis support, with a minimum creatinine clearance of 20 ml/minute), duration of renal-replacement therapy, lengths of stay in the intensive care unit (ICU) and hospital, and days free of nonrenal organ failure were also assessed. 

Results showed that the primary outcome measure, death from any cause by day 60, did not differ between the two groups. Additionally, recovery of renal function and reduction in the rate of nonrenal organ showed no improvement with intensive renal support. The study found no added benefit from an intensive (high-dose) treatment strategy as compared with the more conventional, less-intensive treatment strategy.

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