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

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02258074
First Posted: October 7, 2014
Last Update Posted: November 2, 2017
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.
Information provided by (Responsible Party):
Jennifer Gassman, National Institute of Diabetes and Digestive and Kidney Diseases
July 28, 2014
October 7, 2014
November 2, 2017
March 2015
May 2018   (Final data collection date for primary outcome measure)
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 [ Time Frame: Baseline, Month 12 ]
Same as current
Complete list of historical versions of study NCT02258074 on ClinicalTrials.gov Archive Site
  • Change from baseline in bone and mineral metabolism markers [ Time Frame: Baseline, Month F12 ]
    Bone and mineral metabolism markers assessed by changes in parathyroid hormone (PTH), calcitriol, klotho, N terminal propeptide of Type 1 procollagen (P1NP) and Tartrate-resistant acid phosphatase (Trap-5b) levels over 12 months
  • Change from baseline in surrogate measures of cardiovascular disease (CVD) risk over 12 months [ Time Frame: Baseline, Month F12 ]
    CVD risk assessed by Cardiac Magnetic Resonance Imaging (MRI)-measured changes in left ventricular (LV) mass index, LV end diastolic volume, and left atrial volume.
  • Change from baseline in surrogate measures of CKD progression and inflammation, by changes in intra-renal oxygenation and fibrosis over 12 months [ Time Frame: Baseline, Month F12 ]
    CKD progression and inflammation, by changes in intra-renal oxygenation and fibrosis as assessed by gadolinium-free blood oxygenation level dependent (BOLD) MRI and diffusion-weighted MRI and changes in glomerular filtration (GFR), albuminuria and C reactive protein (CRP) and Interleukin 6 (IL-6) over 12 months.
Same as current
  • Change from baseline in brain natriuretic peptide measure of cardiovascular disease (CVD) risk over 12 months [ Time Frame: baseline, Month F12 ]
    CVD risk assessed by change in level of brain natriuretic peptide (pg/mL) (BNP) from baseline to Month F12.
  • Change from baseline in troponin T measure of cardiovascular risk (CVD) risk over 12 months. [ Time Frame: baseline, Month F12 ]
    CVD risk assessed by change in level of troponin T (ng/mL) from baseline to Month F12.
  • Change from baseline in cholesterol measure of cardiovascular disease (CVD) risk over 12 months [ Time Frame: baseline, Month F12 ]
    CVD risk assessed by change in level of cholesterol (mg/dl) from baseline to Month F12.
  • Change from baseline in asymmetric dimethylarginine (ADMA) measure of cardiovascular disease (CVD) risk over 12 months. [ Time Frame: baseline, Month F12 ]
    CVD risk assessed by change in level of asymmetric dimethylarginine (μmol/L) (ADMA) from baseline to Month F12.
  • Change from baseline bone and mineral marker parathyroid hormone (PTH) over 12 months. [ Time Frame: baseline, Month F12 ]
    Bone and mineral metabolism marker assessed by change in parathyroid hormone (pg/mL) (PTH) levels from baseline to 12 months.
  • Change from baseline bone and mineral marker calcitriol over 12 months. [ Time Frame: baseline, Month F12 ]
    Bone and mineral metabolism marker assessed by change in calcitriol (pg/mL) levels from baseline to 12 months.
  • Change from baseline bone and mineral marker klotho over 12 months. [ Time Frame: baseline, Month F12 ]
    Bone and mineral metabolism marker assessed by change in klotho levels from baseline to 12 months.
  • Change from baseline bone and mineral marker N terminal propeptide of Type 1 procollagen (P1NP) over 12 months. [ Time Frame: baseline, Month F12 ]
    Bone and mineral metabolism marker assessed by change in N terminal propeptide of Type 1 procollagen (pg/mL) (P1NP) levels from baseline to 12 months.
  • Change from baseline bone and mineral marker Tartrate-resistant acid phophatase (Trap-5b) over 12 months. [ Time Frame: baseline, Month F12 ]
    Bone and mineral metabolism marker assessed by change in Tartrate-resistant acid phophatase (U/L) (Trap-5b) levels from baseline to 12 months.
  • Change from baseline in surrogate measures of CKD progression and inflammation, by changes in intra-renal oxygenation and fibrosis over 12 months. [ Time Frame: baseline, Month F12 ]
    CKD progression and inflammation, by changes in intra-renal oxygenation and fibrosis as assessed by gadolinium-free blood oxygenation level dependent (BOLD) MRI and diffusion-weighted MRI.
  • Change from baseline in surrogate measures of CKD progression and inflammation, by changes in glomerular filtration (GFR) over 12 months. [ Time Frame: baseline, Month F12 ]
    CKD progression and inflammation, by changes in intra-renal oxygenation and fibrosis as assessed by glomerular filtration rate mL/min/1.73m2 (GFR) over 12 months.
  • Change from baseline in surrogate measures of CKD progression and inflammation, by changes in albumininuria over 12 months. [ Time Frame: baseline, Month F12 ]
    CKD progression and inflammation, by changes in intra-renal oxygenation and fibrosis as assessed by change in albuminuria over 12 months.
  • Change from baseline in surrogate measures of CKD progression and inflammation, by change in C reative protein (CRP) over 12 months. [ Time Frame: baseline, Month F12 ]
    CKD progression and inflammation, by changes in intra-renal oxygenation and fibrosis as assessed by change in C reative protein (mg/dL) (CRP) over 12 months.
  • Change from baseline in surrogate measures of CKD progression and inflammation, by change in Interleukin 6 (IL-6) over 12 months. [ Time Frame: baseline, Month F12 ]
    CKD progression and inflammation, by changes in intra-renal oxygenation and fibrosis as assessed by change in Interleukin 6 (pg/mL) (IL-6) over 12 months.
Same as current
 
The COMBINE Study: The CKD Optimal Management With BInders and NicotinamidE
The COMBINE Study: The CKD Optimal Management With BInders and NicotinamidE
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.
Not Provided
Interventional
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Other
Chronic Kidney Disease
  • Drug: Nicotinamide
  • Drug: Lanthanum Carbonate
  • 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
  • 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.
    Interventions:
    • 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.
    Interventions:
    • Drug: Lanthanum Carbonate
    • Drug: Placebo (for Nicotinamide)
  • 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.
    Interventions:
    • Drug: Nicotinamide
    • Drug: Placebo (for lanthanum carbonate)
  • 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.
    Interventions:
    • Drug: Placebo (for Nicotinamide)
    • Drug: Placebo (for lanthanum carbonate)
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
205
June 2018
May 2018   (Final data collection date for primary outcome measure)

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)

Sexes Eligible for Study: All
18 Years to 85 Years   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT02258074
DK099877-C
Yes
Not Provided
Not Provided
Jennifer Gassman, National Institute of Diabetes and Digestive and Kidney Diseases
Jennifer Gassman
Not Provided
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
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
October 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP