The COMBINE Study: The CKD Optimal Management With BInders and NicotinamidE
Condition: Chronic Kidney Disease
MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic
Intervention: Nicotinamide; Lanthanum Carbonate; Placebo (for Nicotinamide); Placebo (for lanthanum carbonate)
Intervention description: Sugar pill manufactured to mimic Nicotinamide 750 mg capsule; Sugar pill manufactured to mimic Lanthanum Carbonate 500 mg capsule
Intervention MeSH terms: Niacinamide; Niacin; Nicotinic Acids
Phase: Phase 2
Study type: Interventional
Primary purpose: Other
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 205.0
Sex: All
Minimum age: 18 Years
Maximum age: 85 Years
Healthy volunteers: No

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.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patients with estimated glomerular filtration rate (eGFR) 20-45 ml/min/1.73m2

          2. Age 18-85 years

          3. Serum phosphate ≥ 2.8 mg/dL

          4. Platelet count ≥ 125,000/mm3

          5. Able to provide consent

          6. Able to travel to study visits

          7. Able to eat at least two meals a day

          8. 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:

          1. History of allergic reaction to nicotinamide, niacin (excluding flushing),
             multivitamin preparations, or lanthanum carbonate

          2. 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

          3. Creatine kinase (CK) concentrations > 2 times the upper limit of the local laboratory
             reference range

          4. Major hemorrhagic event within the past six months requiring in-patient admission

          5. Blood or platelet transfusion within the past six months

          6. Secondary hyperparathyroidism (PTH > 5 times the upper limit of normal range for the
             laboratory) or currently taking cinacalcet (Sensipar)

          7. Current, clinically significant malabsorption, as determined at the discretion of the
             site investigator

          8. Anemia (screening Hg < 9.0 g/dl)

          9. Serum albumin < 2.5 mg/dl

         10. Anticipated initiation of dialysis or kidney transplantation within 12 months as
             assessed by and at the discretion of the site investigator.

         11. Use of immunosuppressive medications (stable oral steroids ≤ 10 mg of prednisone/day
             or inhaled steroids are exempted)

         12. In the opinion of the site investigator, active abuse of alcohol or drugs

         13. 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.

         14. Current or recent treatment (within the last 14 days) with phosphate binder or
             niacin/nicotinamide > 100 mg/day

         15. Current participation in another clinical trial or other interventional research

         16. Currently taking investigational drugs

         17. Institutionalized individuals, including prisoners and nursing home residents

         18. Malignancy requiring therapy within 2 years (basal or squamous cell skin carcinoma and
             localized prostate cancer are exempted)

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