The CKD Optimal Management With BInders and NicotinamidE (COMBINE)
Number of Subjects in Study Archive: Estimated to be 200
Study Design: Clinical Trial
Conditions: Kidney Diseases
Duration: March 2015 - present
# Recruitment Centers: 7
Treatment: Nicotinamide, Lanthanum Carbonate
Available Genotype Data: No
Image Summary: No
Transplant Type: None
Does it have dialysis patients: No
Clinical Trials URL: https://clinicaltrials.gov/ct2/show/NCT02258074
Phosphorus, a mineral found in many foods, works with calcium and vitamin D to keep bones healthy. Healthy kidneys keep the right balance of phosphorus in the body. Fibroblast growth factor 23 (FGF23) is a hormone that helps the kidneys to control the blood levels of phosphorus.
In people with chronic kidney disease, kidneys struggle to get rid of enough phosphorus, so FGF23 levels increase in the blood to help get rid of extra phosphorus. Over time, with progressive loss of kidney function, both phosphorus and FGF23 can build up in the blood simultaneously. Researchers believe that too much phosphorus and FGF23 in the blood may lead to weak bones, increase the risk of heart problems, and accelerate progression of kidney disease. However, the best way to control phosphorus and FGF23 levels in the blood in patients with chronic kidney disease is not known.
COMBINE is a study to determine new methods to lower serum phosphorus levels and levels of FGF23 in chronic kidney disease patients.
- To test the effectiveness of the study drugs, nicotinamide and lanthanum carbonate, either individually or in combination, to lower blood levels of phosphorus and FGF23.
- To determine the tolerability and safety of the study drugs, nicotinamide and lanthanum carbonate, either individually or in combination, over 12 months in patients with chronic kidney disease.
- To perform cardiac and renal MRI scans without contrast to evaluate the intrinsic renal function and chambers of the heart in response to study procedures.
As a pilot study, the primary outcome measure is feasibility. The clinical outcome measure is change from baseline to 12 months in serum phosphate and FGF23 levels.
Secondary Outcome Measures:
Change from baseline in bone and mineral metabolism markers.
Change from baseline in surrogate measures of cardiovascular disease (CVD) risk over 12 months.
Change from baseline in surrogate measures of CKD progression and inflammation, by changes in intra-renal oxygenation and fibrosis over 12 months
Other outcome measures are documented in the Clinical Trials URL.
Adults between the ages of 18 and 85 years old, with an estimated glomerular filtration rate (eGFR) 20-45 ml/min/1.73m2, a serum phosphate ≥ 2.8 mg/dL, a platelet count ≥ 125,000/mm3, and able to eat at least two meals a day.
Adults with a history of allergic reaction to nicotinamide, niacin, multivitamin preparations, or lanthum carbonate; creatinine kinase concentrations > 2 times the upper limit of the local laboratory reference range; major hemorrhagic event within the past six months requiring in-patient admission; blood or platelet transfusion within the past six months; secondary hyperparathyroidism or currently taking cinacalcet; anemia; serum albumin < 2.5 mg/dl; current, clinically significant malabsorption; anticipated initiation of dialysis or kidney transplantation with 12 months; use of immunosuppressive medications; active abuse of alcohol or drugs; malignancy requiring therapy within 2 years; currently taking investigational drugs; currently participating in another clinical trial or interventional research; current or recent treatment with phosphate binder or niacin/nicotinamide; recent initiation or change in dose of treatment with 1,25 (OH)2 vitamin D or active vitamin D analogues (paricalcitol or hectorol); liver disease, defined as known cirrhosis by imaging or physician diagnosis, documented alcohol use > 14 drinks/week, or aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, or total bilirubin concentrations > 2 times the upper limit of the local laboratory reference range; and institutionalized individuals.
This study is ongoing.