The COMBINE Study: The CKD Optimal Management With BInders and NicotinamidE
NCT ID: NCT02258074
Last Updated: 2021-08-02
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE2
205 participants
INTERVENTIONAL
2015-03-31
2019-09-30
Brief Summary
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
OTHER
TRIPLE
Study Groups
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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.
Nicotinamide
Lanthanum Carbonate
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.
Lanthanum Carbonate
Placebo (for Nicotinamide)
Sugar pill manufactured to mimic Nicotinamide 750 mg capsule
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.
Nicotinamide
Placebo (for lanthanum carbonate)
Sugar pill manufactured to mimic Lanthanum Carbonate 500 mg capsule
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.
Placebo (for Nicotinamide)
Sugar pill manufactured to mimic Nicotinamide 750 mg capsule
Placebo (for lanthanum carbonate)
Sugar pill manufactured to mimic Lanthanum Carbonate 500 mg capsule
Interventions
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Nicotinamide
Lanthanum Carbonate
Placebo (for Nicotinamide)
Sugar pill manufactured to mimic Nicotinamide 750 mg capsule
Placebo (for lanthanum carbonate)
Sugar pill manufactured to mimic Lanthanum Carbonate 500 mg capsule
Eligibility Criteria
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Inclusion Criteria
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
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)
\-
18 Years
85 Years
ALL
No
Sponsors
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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
NIH
The Cleveland Clinic
OTHER
Responsible Party
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Jennifer Gassman, PhD
Principal Investigator-Data Coordinating Center
Principal Investigators
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Michael F. Flessner, MD, PhD
Role: STUDY_DIRECTOR
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
John W. Kusek, PhD
Role: STUDY_DIRECTOR
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Jennifer J Gassman, Ph.D.
Role: PRINCIPAL_INVESTIGATOR
Data Coordinating Center, Cleveland Clinic
Linda F Fried, MD
Role: STUDY_CHAIR
University of Pittsburgh
Locations
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University of California at San Diego
San Diego, California, United States
Denver Nephrology Research
Denver, Colorado, United States
George Washington University
Washington D.C., District of Columbia, United States
NorthShore University Health System
Chicago, Illinois, United States
Northwestern University
Chicago, Illinois, United States
University of Utah
Salt Lake City, Utah, United States
Utah VA
Salt Lake City, Utah, United States
Countries
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References
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Isakova T, Ix JH, Sprague SM, Raphael KL, Fried L, Gassman JJ, Raj D, Cheung AK, Kusek JW, Flessner MF, Wolf M, Block GA. Rationale and Approaches to Phosphate and Fibroblast Growth Factor 23 Reduction in CKD. J Am Soc Nephrol. 2015 Oct;26(10):2328-39. doi: 10.1681/ASN.2015020117. Epub 2015 May 12.
Ix JH, Isakova T, Larive B, Raphael KL, Raj DS, Cheung AK, Sprague SM, Fried LF, Gassman JJ, Middleton JP, Flessner MF, Block GA, Wolf M. Effects of Nicotinamide and Lanthanum Carbonate on Serum Phosphate and Fibroblast Growth Factor-23 in CKD: The COMBINE Trial. J Am Soc Nephrol. 2019 Jun;30(6):1096-1108. doi: 10.1681/ASN.2018101058. Epub 2019 May 13.
Natale P, Green SC, Ruospo M, Craig JC, Vecchio M, Elder GJ, Strippoli GF. Phosphate binders for preventing and treating chronic kidney disease-mineral and bone disorder (CKD-MBD). Cochrane Database Syst Rev. 2025 Jun 27;6(6):CD006023. doi: 10.1002/14651858.CD006023.pub4.
Trujillo J, Alotaibi M, Seif N, Cai X, Larive B, Gassman J, Raphael KL, Cheung AK, Raj DS, Fried LF, Sprague SM, Block G, Chonchol M, Middleton JP, Wolf M, Ix JH, Prasad P, Isakova T, Srivastava A. Associations of Kidney Functional Magnetic Resonance Imaging Biomarkers with Markers of Inflammation in Individuals with CKD. Kidney360. 2024 May 1;5(5):681-689. doi: 10.34067/KID.0000000000000437. Epub 2024 Apr 4.
Srivastava A, Cai X, Lee J, Li W, Larive B, Kendrick C, Gassman JJ, Middleton JP, Carr J, Raphael KL, Cheung AK, Raj DS, Chonchol MB, Fried LF, Block GA, Sprague SM, Wolf M, Ix JH, Prasad PV, Isakova T. Kidney Functional Magnetic Resonance Imaging and Change in eGFR in Individuals with CKD. Clin J Am Soc Nephrol. 2020 Jun 8;15(6):776-783. doi: 10.2215/CJN.13201019. Epub 2020 Apr 28.
Provided Documents
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Document Type: Study Protocol and Statistical Analysis Plan
Document Type: Informed Consent Form
Other Identifiers
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DK099877-C
Identifier Type: -
Identifier Source: org_study_id
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