The MAPP II Study of Urologic Chronic Pelvic Pain Syndrome: The Trans-MAPP Symptom Patterns Study (MAPP II)

General Description

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

Objectives

Primary objectives:

• Identify clinical features, participant-reported characteristics, and biological measurements (e.g., biomarkers, central nervous system structure/function, microbial populations and patterns) assessed at baseline and during follow-up, that predict or are strongly associated with UCPPS symptom patterns and risk
• Characterize potential clinical and biological changes (e.g., regional versus systemic pain profiles, inflammatory state, function of the central nervous system) associated with changes in symptoms to reveal underlying physiological contributors to improvement or worsening
• Further characterize and validate UCPPS symptom patterns and symptom impact as clinically significant and patient-valued measures
• Establish and validate phenotypic subgroups of UCPPS participants based on diverse urologic and non-urologic symptoms and corresponding biological (pathophysiological) features
• Develop statistical models for clinical use in predicting differential longitudinal patterns of UCPPS symptoms
• Create a National resource of clinical data and associated biological samples and measures for supporting future investigator-initiated studies of UCPPS

Outcome Measure

As an observational cohort study, the MAPP Network utilized a variety of urologic and non-urologic clinical measures and biological assessments to define UCPPS, including for symptom change, risk, and to establish distinct UCPPS sub-phenotypes. These included standard measures, as well as the MAPP Network-derived Pain Severity Score (PSS) and the Urinary Severity Score (USS). The Pain Severity Score was constructed from the Genitourinary Pain Index (GUPI) pain subscale score and the Interstitial Cystitis Symptom Index (ICSI) bladder pain score. The Urinary Severity Score was constructed from the GUPI urinary subscale score and several scores from the ICSI. In addition, distinct pain profiles were described using a MAPP-modified Body Pain Map and assessments of co-occurring pain conditions using the MAPP Network CMSI module. Complete lists of diverse MAPP Network measures may be found in network publications and the MAPP Network data dictionary.

Criteria

Inclusion criteria:

• At least 18 years of age
• In the past 3 months, participant had a feeling of pain, pressure, or discomfort in the lower abdomen or pelvic area the majority of the time
• Participant reported a response of at least 1 on the pain, pressure, or discomfort scale for UCPPS symptoms during the past 2 weeks
• Participant received a clinical diagnosis of either or both IC/BPS or CP/CPPS (per AUA guidelines) or a clinician familiar with UCPPS criteria confirmed participant met criteria

Exclusion criteria:

• Ongoing symptomatic urethral stricture, or neurological disease or disorder affecting the bladder or bowel fistula
• History of cystitis caused by tuberculosis, radiation therapy, or Cytoxan/cyclophosphamide therapy; or history of cancer (with the exception of skin cancer)
• Participant had augmentation cystoplasty or cystectomy
• An active autoimmune or infectious disorder (such as Crohn's Disease or Ulcerative Colitis, Lupus, Rheumatoid Arthritis, Multiple Sclerosis, or HIV); severe cardiac, pulmonary, renal, or hepatic disease; or major psychiatric disorder or other psychiatric or medical issues that would interfere with study participation
• Diagnosis of unilateral orchalgia, without pelvic symptoms (for males only)
• History of transurethral microwave thermotherapy (TUMT), transurethral needle ablation (TUNA), balloon dilation, prostate cryo-surgery, or laser procedure (for males only)

Outcome

Characterization of UCPPS participants revealed and further validated distinct phenotypic sub-groups based on the degree of widespread pain, urologic and pain severity profiles, presence of co-occurring pain conditions, and bladder pain qualities. Biological factors (e.g., immune, neurobiological) and diverse psychosocial variables were found to correlate with these phenotypes, as well. Symptom patterns analyses revealed initial phases of improving or worsening (or stable symptoms) for some participants followed by slow change or for many participants stabilization of symptoms over time. Ongoing analyses of MAPP II data are underway to describe associations between identified clinical phenotypes and differential response to therapies (e.g., locally versus systemic acting) received as standard of care. Interested readers should refer to network publications for a comprehensive description of seminal MAPP Network findings.