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Trial record 19 of 49 for:    Recruiting, Not yet recruiting, Available Studies | kidney disease | NIDDK

Nicotinamide Riboside Supplementation for Treating Arterial Stiffness and Elevated Systolic Blood Pressure in Patients With Moderate to Severe CKD

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ClinicalTrials.gov Identifier: NCT04040959
Recruitment Status : Not yet recruiting
First Posted : August 1, 2019
Last Update Posted : August 26, 2019
Sponsor:
Collaborator:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
University of Colorado, Denver

Brief Summary:

Risk of cardiovascular diseases (CVD) is significantly elevated in patients with chronic kidney disease (CKD); however, this increased risk is only partially explained by traditional CV risk factors. Arterial dysfunction is an important nontraditional CV risk factor gaining increased recognition in the field of nephrology. This process is best represented, both physiologically and pathophysiologically, by increases in the gold standard measure of arterial stiffening, carotid to femoral artery pulse wave velocity (CFPWV), which reflects, in particular, increases in aortic stiffness. Aortic stiffening with CKD is mediated by structural and functional (increased vascular smooth muscle tone) changes in the arterial wall stimulated by oxidative stress and chronic low-grade inflammation. Caloric restriction (CR) is a promising strategy for prevention of CKD-associated arterial dysfunction and CVD. However, long-term adherence to chronic CR regimens with optimal nutrition is very difficult to achieve. We have shown that boosting NAD+ bioavailability to stimulate SIRT-1, a "CR mimetic" approach, reduces CFPW and oxidative stress in old mice, and we recently took the first step in translating these findings in a study of adults with normal kidney function and elevated systolic blood pressure (SBP). We found that supplementation with nicotinamide riboside, a natural, commercially available precursor of NAD+ and novel CR mimetic, increased NAD+ bioavailability and reduced CFPWV and SBP. Here we propose a randomized, placebo-controlled, double-blind, single-site phase IIa clinical trial to assess the safety and efficacy of oral nicotinamide riboside (500 mg capsules 2x/day; NIAGEN®; ChromaDex Inc.) for 3 months vs. placebo for decreasing aortic stiffness and SBP in patients (35-80 years) with stage III and IV CKD. We hypothesize that treatment will reduce CFPWV and SBP, as related to increases in systemic NAD+ bioavailability and reductions in oxidative stress, and inflammation.

Aim 1: To measure CFPWV (primary outcome) before/after nicotinamide riboside vs. placebo treatment; Aim 2: To measure casual and 24h-ambulatory SBP (secondary outcome) before and after treatment; Aim 3: To determine the safety and tolerability of treatment with nicotinamide riboside vs. placebo; Aim 4: To measure systemic NAD+ and NAD+-related metabolite concentrations, as well as circulating markers of oxidative stress, inflammation, and vasoconstriction factors before and after treatment.


Condition or disease Intervention/treatment Phase
Vascular Diseases Kidney Disease Blood Pressure Oxidative Stress Drug: Nicotinamide riboside Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 118 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Nicotinamide Riboside Supplementation for Treating Arterial Stiffness and Elevated Systolic Blood Pressure in Patients With Moderate to Severe CKD
Estimated Study Start Date : September 15, 2019
Estimated Primary Completion Date : May 15, 2024
Estimated Study Completion Date : September 15, 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Nicotinamide Riboside
Each nicotinamide riboside capsule contains 250 mg of nicotinamide riboside chloride mixed with microcrystalline cellulose. Dosage: 500 mg by mouth twice a day for 3 months.
Drug: Nicotinamide riboside
Nicotinamide riboside is a naturally occurring vitamin B3 derivative found in yeast, bacteria, and mammalian tissues, and also has been detected in cows' milk.

Placebo Comparator: Placebo
Matched placebo capsules.
Drug: Nicotinamide riboside
Nicotinamide riboside is a naturally occurring vitamin B3 derivative found in yeast, bacteria, and mammalian tissues, and also has been detected in cows' milk.




Primary Outcome Measures :
  1. carotid-femoral pulse wave velocity [ Time Frame: Baseline and 3 months ]
    change in carotid-femoral pulse wave velocity


Secondary Outcome Measures :
  1. Systolic blood pressure [ Time Frame: Baseline and 3 months ]
    Casual blood pressure

  2. Systolic blood pressure [ Time Frame: Baseline and 3 months ]
    24h ambulatory blood pressure


Other Outcome Measures:
  1. Number of participants with treatment-related adverse events as assessed by Common Terminology Criteria for Adverse Events v4.0 [ Time Frame: weeks 2, 4, 6, 8, 10, and 12 ]
    Safety and tolerability of the intervention

  2. Change in blood cellular NAD+ metabolism [ Time Frame: baseline and 3 months ]
    Assessment of the "NAD+ metabolome" in circulating PBMCs



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Ages Eligible for Study:   35 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age 35-80 years;
  • Ability to provide informed consent;
  • Willing to accept random assignment to condition;
  • CKD stage III or IV (eGFR with the 4-variable MDRD prediction equation: 20-60 mL/min/1.73m2; stable renal function in the past 3 months);
  • Blood pressure controlled to <140/90 mmHg for the past 3 months;
  • Body mass index <40 kg/m2;
  • Weight stable in the prior 3 months (<2 kg weight change) and willing to remain weight stable throughout the study

Exclusion Criteria:

  • Patients with advanced CKD requiring chronic dialysis;
  • Significant co-morbid conditions that lead the investigator to conclude that life expectancy < 1 year;
  • History of severe congestive heart failure (i.e., ejection fraction < 35%);
  • Hospitalization in the past month;
  • Proteinuria > 5 g/day;
  • Immunosuppressant agents such as cyclosporine, tacrolimus, azathioprine, etanercept, infliximab, adalimumab, anakinra or long-term oral glucocorticoids taken in past 12 months;
  • Known malignancy;
  • Woman who are pregnant, nursing or planning to become pregnant;
  • Special classes of subjects considered vulnerable populations will not be included in the study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04040959


Contacts
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Contact: Michel Chonchol, MD 303-724-7796 Michel.Chonchol@ucdenver.edu
Contact: Beverly Farmer, RN 303-724-7797 Beverly.Farmer@ucdenver.edu

Locations
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United States, Colorado
UColorado
Aurora, Colorado, United States, 80045
Sponsors and Collaborators
University of Colorado, Denver
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators
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Principal Investigator: Michel Chonchol, MD University of Colorado, Denver

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Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT04040959     History of Changes
Other Study ID Numbers: 19-0149
R01DK121516-01 ( U.S. NIH Grant/Contract )
First Posted: August 1, 2019    Key Record Dates
Last Update Posted: August 26, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University of Colorado, Denver:
stiffness
chronic kidney disease
Hypertension
Additional relevant MeSH terms:
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Kidney Diseases
Vascular Diseases
Urologic Diseases
Cardiovascular Diseases
Niacinamide
Niacin
Nicotinic Acids
Vitamin B Complex
Vitamins
Micronutrients
Nutrients
Growth Substances
Physiological Effects of Drugs
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Vasodilator Agents