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

Chronic Kidney Disease Clinical Trial

— COMBINE  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02258074
• Other study ID #: DK099877-C
• Secondary ID: U01DK099877
• Status: Completed
• Phase: Phase 2
• Start date: March 2015
• Est. completion date: September 2019

Study information

• Verified date: July 2021
• Source: The Cleveland Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 205
• Est. completion date: September 2019
• Est. primary completion date: November 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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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Related Conditions & MeSH terms

• Chronic Kidney Disease
• Kidney Diseases
• Renal Insufficiency, Chronic

Intervention

Drug:
• 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

Locations

Country	Name	City	State
United States	NorthShore University Health System	Chicago	Illinois
United States	Northwestern University	Chicago	Illinois
United States	Denver Nephrology Research	Denver	Colorado
United States	University of Utah	Salt Lake City	Utah
United States	Utah VA	Salt Lake City	Utah
United States	University of California at San Diego	San Diego	California
United States	George Washington University	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
The Cleveland Clinic	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

References & Publications (2)

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. Review. — View 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 COMBIN — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	FGF23	Change from baseline to 12 months in FGF23 level.	Baseline to 12 months
Primary	Serum Phosphate (mg/dl)	Change from Baseline to 12 months in serum phosphate level	Baseline to 12 months