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

Condition(s) targeted: Chronic Kidney Disease

Intervention: Nicotinamide (Drug); Lanthanum Carbonate (Drug); Placebo (for Nicotinamide) (Drug); Placebo (for lanthanum carbonate) (Drug)

Phase: Phase 3

Status: Recruiting

Sponsored by: John Kusek

Official(s) and/or principal investigator(s):
Michael F. Flessner, MD, PhD, Study Director, Affiliation: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
John W. Kusek, PhD, Study Director, Affiliation: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Jennifer J Gassman, Ph.D., Principal Investigator, Affiliation: Data Coordinating Center, Cleveland Clinic
Linda F Fried, MD, Study Chair, Affiliation: University of Pittsburgh

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

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator)

Primary outcome: Since this is a Pilot Study, the primary outcome measures is feasibility. The clinical outcome measure is change from baseline to 12 months in serum phosphate and FGF23 levels

Secondary outcome:

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

Minimum age: 18 Years. Maximum age: 85 Years. Gender(s): Both.

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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University of California at San Diego, San Diego, California 92161, United States; Recruiting
Joachim Ix, M.D., Phone: 858-552-8585, Ext: 1657
Joachim Ix, MD, Principal Investigator

Denver Nephrology Research, Denver, Colorado 80230, United States; Recruiting
Martha Persky, RN, Phone: 303-364-4775, Email: mpersky@dnresearch.org
Geoffrey Block, MD, Principal Investigator

George Washington University, Washington, District of Columbia 20037, United States; Recruiting
Maria Wing, Ph.D., Phone: 202-741-2220, Email: mwing@mfa.gwu.edu
Dominic Raj, MD, Principal Investigator

NorthShore University Health System, Chicago, Illinois 60201, United States; Recruiting
Fettman Shonny, RN, MS, CCRP, Phone: 847-570-1761, Email: sfettman@northshore.org
Stuart Sprague, DO, Principal Investigator

Northwestern University, Chicago, Illinois 60611, United States; Recruiting
Michelle Bradley, MPH, CCRP, Phone: 312-503-1909, Email: michelle.bradley@northwestern.edu
Myles Wolf, MD, Principal Investigator
Tamara Isakova, MD, Sub-Investigator

University of Utah, Salt Lake City, Utah 84112, United States; Recruiting
Jennifer Zitterkoph, Phone: 801-585-1897, Email: Jennifer.zitterkoph@hsc.utah.edu
Alfred Cheung, MD, Principal Investigator
Kalani Raphael, MD, Principal Investigator

Utah VA, Salt Lake City, Utah 84112, United States; Recruiting
Katt Mackin, Phone: 801-582-1565, Ext: 1798, Email: Katherine.mackin@hsc.utah.edu
Kalani Raphael, MD, Principal Investigator
Alfred Cheung, MD, Principal Investigator

Starting date: March 2015
Last updated: March 30, 2015