The COMBINE Study: The CKD Optimal Management With BInders and NicotinamidE

Phase 2

Completed

Conditions: Chronic Kidney Disease

Interventions: Drug: Nicotinamide
Drug: Placebo (for Nicotinamide)
Drug: Placebo (for lanthanum carbonate)
Drug: Lanthanum Carbonate

Registration Number: NCT02258074

Lead Sponsor: The Cleveland Clinic

Brief Summary: The COMBINE clinical trial is a pilot study evaluating the effects of nicotinamide and lanthanum carbonate on serum phosphate and fibroblast growth factor 23 (FGF23) in patients with Chronic Kidney Disease (CKD) stages 3-4.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 205

Inclusion Criteria

Patients with estimated glomerular filtration rate (eGFR) 20-45 ml/min/1.73m2
Age 18-85 years
Serum phosphate ≥ 2.8 mg/dL
Platelet count ≥ 125,000/mm3
Able to provide consent
Able to travel to study visits
Able to eat at least two meals a day
In the opinion of the site investigator, willing and able to follow the study treatment regimen and comply with the site investigator's recommendations.

Exclusion Criteria

History of allergic reaction to nicotinamide, niacin (excluding flushing), multivitamin preparations, or lanthanum carbonate
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
Creatine kinase (CK) 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 (PTH > 5 times the upper limit of normal range for the laboratory) or currently taking cinacalcet (Sensipar)
Current, clinically significant malabsorption, as determined at the discretion of the site investigator
Anemia (screening Hg < 9.0 g/dl)
Serum albumin < 2.5 mg/dl
Anticipated initiation of dialysis or kidney transplantation within 12 months as assessed by and at the discretion of the site investigator.
Use of immunosuppressive medications (stable oral steroids ≤ 10 mg of prednisone/day or inhaled steroids are exempted)
In the opinion of the site investigator, active abuse of alcohol or drugs
Recent (within the last 14 days) initiation or change in dose of treatment with 1,25 (OH)2 vitamin D or active vitamin D analogues (paricalcitol or hectorol). Patients on stable doses of these agents initiated more than 14 days prior to screening are eligible to participate.
Current or recent treatment (within the last 14 days) with phosphate binder or niacin/nicotinamide > 100 mg/day
Current participation in another clinical trial or other interventional research
Currently taking investigational drugs
Institutionalized individuals, including prisoners and nursing home residents
Malignancy requiring therapy within 2 years (basal or squamous cell skin carcinoma and localized prostate cancer are exempted)

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Lanthanum carbonate + nicotinamide placebo	Placebo (for Nicotinamide)	Two lanthanum carbonate 500 mg capsules by mouth with each meal (3000 mg) for 12 months. One Placebo (for nicotinamide) 750 mg capsule by mouth twice daily (1500 mg) for 12 months.
Lanthanum carbonate placebo and nicotinamide	Placebo (for lanthanum carbonate)	One nicotinamide 750 mg capsule by mouth twice daily (1500 mg) for 12 months. Two Placebo (for lanthanum carbonate) 500 mg capsules by mouth with each meal (3000 mg) for 12 months.
Lanthanum carbonate placebo and nicotinamide placebo	Placebo (for Nicotinamide)	One Placebo (for nicotinamide) 750 mg capsule by mouth twice daily (1500 mg) for 12 months. Two Placebo (for lanthanum carbonate) 500 mg capsules by mouth with each meal (3000 mg) for 12 months.
Lanthanum carbonate placebo and nicotinamide placebo	Placebo (for lanthanum carbonate)	One Placebo (for nicotinamide) 750 mg capsule by mouth twice daily (1500 mg) for 12 months. Two Placebo (for lanthanum carbonate) 500 mg capsules by mouth with each meal (3000 mg) for 12 months.
Lanthanum carbonate + nicotinamide	Lanthanum Carbonate	One nicotinamide 750 mg capsule by mouth twice daily (1500 mg) for 12 months. Two lanthanum carbonate 500 mg capsules by mouth with each meal (3000 mg) for 12 months.
Lanthanum carbonate + nicotinamide	Nicotinamide	One nicotinamide 750 mg capsule by mouth twice daily (1500 mg) for 12 months. Two lanthanum carbonate 500 mg capsules by mouth with each meal (3000 mg) for 12 months.
Lanthanum carbonate + nicotinamide placebo	Lanthanum Carbonate	Two lanthanum carbonate 500 mg capsules by mouth with each meal (3000 mg) for 12 months. One Placebo (for nicotinamide) 750 mg capsule by mouth twice daily (1500 mg) for 12 months.
Lanthanum carbonate placebo and nicotinamide	Nicotinamide	One nicotinamide 750 mg capsule by mouth twice daily (1500 mg) for 12 months. Two Placebo (for lanthanum carbonate) 500 mg capsules by mouth with each meal (3000 mg) for 12 months.

Primary Outcome Measures

Name	Time	Method
Serum Phosphate (mg/dl)	Baseline to 12 months	Change from Baseline to 12 months in serum phosphate level
FGF23	Baseline to 12 months	Change from baseline to 12 months in FGF23 level.

Secondary Outcome Measures

Name	Time	Method

Trial Locations

Locations (7): NorthShore University Health System
🇺🇸
Chicago, Illinois, United States
Denver Nephrology Research
🇺🇸
Denver, Colorado, United States
Northwestern University
🇺🇸
Chicago, Illinois, United States
University of California at San Diego
🇺🇸
San Diego, California, United States
George Washington University
🇺🇸
Washington, District of Columbia, United States
Utah VA
🇺🇸
Salt Lake City, Utah, United States
University of Utah
🇺🇸
Salt Lake City, Utah, United States