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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02258074
Recruitment Status : Completed
First Posted : October 7, 2014
Results First Posted : July 30, 2021
Last Update Posted : August 2, 2021
Sponsor:
Collaborator:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
Jennifer Gassman, PhD, 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.

Condition or disease Intervention/treatment Phase
Chronic Kidney Disease Drug: Nicotinamide Drug: Lanthanum Carbonate Drug: Placebo (for Nicotinamide) Drug: Placebo (for lanthanum carbonate) Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 205 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Other
Official Title: The COMBINE Study: The CKD Optimal Management With BInders and NicotinamidE
Actual Study Start Date : March 2015
Actual Primary Completion Date : November 2018
Actual Study Completion Date : September 2019


Arm Intervention/treatment
Experimental: Lanthanum carbonate + 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.
Drug: Nicotinamide
Drug: Lanthanum Carbonate
Placebo Comparator: Lanthanum carbonate + nicotinamide placebo
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
Drug: Placebo (for Nicotinamide)
Sugar pill manufactured to mimic Nicotinamide 750 mg capsule

Active Comparator: Lanthanum carbonate placebo and 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.
Drug: Nicotinamide
Drug: Placebo (for lanthanum carbonate)
Sugar pill manufactured to mimic Lanthanum Carbonate 500 mg capsule

Placebo Comparator: Lanthanum carbonate placebo and nicotinamide placebo
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)
Sugar pill manufactured to mimic Nicotinamide 750 mg capsule

Drug: Placebo (for lanthanum carbonate)
Sugar pill manufactured to mimic Lanthanum Carbonate 500 mg capsule




Primary Outcome Measures :
  1. FGF23 [ Time Frame: Baseline to 12 months ]
    Change from baseline to 12 months in FGF23 level.

  2. Serum Phosphate (mg/dl) [ Time Frame: Baseline to 12 months ]
    Change from Baseline to 12 months in serum phosphate level



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02258074


Locations
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United States, California
University of California at San Diego
San Diego, California, United States, 92161
United States, Colorado
Denver Nephrology Research
Denver, Colorado, United States, 80230
United States, District of Columbia
George Washington University
Washington, District of Columbia, United States, 20037
United States, Illinois
NorthShore University Health System
Chicago, Illinois, United States, 60201
Northwestern University
Chicago, Illinois, United States, 60611
United States, Utah
University of Utah
Salt Lake City, Utah, United States, 84112
Utah VA
Salt Lake City, Utah, United States, 84112
Sponsors and Collaborators
The Cleveland Clinic
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators
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Study Director: Michael F. Flessner, MD, PhD National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Study Director: John W. Kusek, PhD National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Principal Investigator: Jennifer J Gassman, Ph.D. Data Coordinating Center, Cleveland Clinic
Study Chair: Linda F Fried, MD University of Pittsburgh
  Study Documents (Full-Text)

Documents provided by Jennifer Gassman, PhD, The Cleveland Clinic:
Informed Consent Form  [PDF] December 7, 2015

Publications of Results:
Other Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Jennifer Gassman, PhD, Principal Investigator-Data Coordinating Center, The Cleveland Clinic
ClinicalTrials.gov Identifier: NCT02258074    
Other Study ID Numbers: DK099877-C
U01DK099877 ( U.S. NIH Grant/Contract )
First Posted: October 7, 2014    Key Record Dates
Results First Posted: July 30, 2021
Last Update Posted: August 2, 2021
Last Verified: July 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: The study data will be archived in the NIDDK Data Repository.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Analytic Code
Time Frame: We anticipate that the data and documentation will be provided to the NIDDK Data Repository in March 2020 and will become available approximately six months later.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Kidney Diseases
Renal Insufficiency, Chronic
Urologic Diseases
Renal Insufficiency
Niacinamide
Niacin
Nicotinic Acids
Vitamin B Complex
Vitamins
Micronutrients
Physiological Effects of Drugs
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Vasodilator Agents