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

Study Overview
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Brief Summary
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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.

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

Conditions
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Chronic Kidney Disease

Intervention / Treatment
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* Drug: Nicotinamide
* Drug: Lanthanum Carbonate
* Drug: Placebo (for Nicotinamide)
* Drug: Placebo (for lanthanum carbonate)


Participation Criteria
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Eligibility Criteria
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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) -

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lanthanum carbonate + nicotinamide<br>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. | Drug: Nicotinamide<br> <br> Drug: Lanthanum Carbonate<br> <br> |
| Placebo Comparator: Lanthanum carbonate + nicotinamide placebo<br>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. | Drug: Lanthanum Carbonate<br> <br> Drug: Placebo (for Nicotinamide)<br>* Sugar pill manufactured to mimic Nicotinamide 750 mg capsule<br>|
| Active Comparator: Lanthanum carbonate placebo and nicotinamide<br>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. | Drug: Nicotinamide<br> <br> Drug: Placebo (for lanthanum carbonate)<br>* Sugar pill manufactured to mimic Lanthanum Carbonate 500 mg capsule<br>|
| Placebo Comparator: Lanthanum carbonate placebo and nicotinamide placebo<br>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. | Drug: Placebo (for Nicotinamide)<br>* Sugar pill manufactured to mimic Nicotinamide 750 mg capsule<br>Drug: Placebo (for lanthanum carbonate)<br>* Sugar pill manufactured to mimic Lanthanum Carbonate 500 mg capsule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| FGF23 | Change from baseline to 12 months in FGF23 level. | Baseline to 12 months | 
| Serum Phosphate (mg/dl) | Change from Baseline to 12 months in serum phosphate level | Baseline to 12 months |