Trial record 9 of 329 for:    nicotinamide

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

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified July 2014 by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Sponsor:
Information provided by (Responsible Party):
John Kusek, National Institute of Diabetes and Digestive and Kidney Diseases
ClinicalTrials.gov Identifier:
NCT02258074
First received: July 28, 2014
Last updated: October 2, 2014
Last verified: July 2014
  Purpose

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 Intervention Phase
Chronic Kidney Disease
Drug: Nicotinamide
Drug: Lanthanum Carbonate
Drug: Placebo (for Nicotinamide)
Drug: Placebo (for lanthanum carbonate)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Official Title: The COMBINE Study: The CKD Optimal Management With BInders and NicotinamidE

Resource links provided by NLM:


Further study details as provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change from baseline in bone and mineral metabolism markers [ Time Frame: Baseline, Month F12 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.


Other Outcome Measures:
  • Change from baseline in brain natriuretic peptide measure of cardiovascular disease (CVD) risk over 12 months [ Time Frame: baseline, Month F12 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 200
Study Start Date: January 2015
Estimated Study Completion Date: June 2018
Estimated Primary Completion Date: May 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Both
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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  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02258074

Locations
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
John Kusek
Investigators
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
  More Information

No publications provided

Responsible Party: John Kusek, Program Director, NIDDK-KUH, National Institute of Diabetes and Digestive and Kidney Diseases
ClinicalTrials.gov Identifier: NCT02258074     History of Changes
Other Study ID Numbers: DK099877-C
Study First Received: July 28, 2014
Last Updated: October 2, 2014
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Niacin
Niacinamide
Nicotinic Acids
Kidney Diseases
Renal Insufficiency, Chronic
Renal Insufficiency
Urologic Diseases
Antimetabolites
Cardiovascular Agents
Growth Substances
Hypolipidemic Agents
Lipid Regulating Agents
Micronutrients
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses
Vasodilator Agents
Vitamin B Complex
Vitamins

ClinicalTrials.gov processed this record on October 20, 2014