Clinical trial NCT02258074: The COMBINE Study: The CKD Optimal Management With BInders and NicotinamidE
Official title: The COMBINE Study: The CKD Optimal Management With BInders and NicotinamidE
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Kidney Disease
Lead sponsor: The Cleveland Clinic
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2014-10-07
Enrollment: 205
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.


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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Primary outcomes:
measure: FGF23
timeFrame: Baseline to 12 months
measure: Serum Phosphate (mg/dl)
timeFrame: Baseline to 12 months
Secondary outcomes:
Other outcomes:
Locations:
city: San Diego
country: United States
facility: University of California at San Diego
state: California
city: Denver
country: United States
facility: Denver Nephrology Research
state: Colorado
city: Washington
country: United States
facility: George Washington University
state: District of Columbia
city: Chicago
country: United States
facility: NorthShore University Health System
state: Illinois
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Salt Lake City
country: United States
facility: Utah VA
state: Utah
Study officials:
affiliation: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
name: Michael F. Flessner, MD, PhD
role: STUDY_DIRECTOR
affiliation: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
name: John W. Kusek, PhD
role: STUDY_DIRECTOR
affiliation: Data Coordinating Center, Cleveland Clinic
name: Jennifer J Gassman, Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Pittsburgh
name: Linda F Fried, MD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.