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

NCT04040959 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 19-0149R01DK121516-01
• Study Type: interventional
• Target: 118
• Locations: 1 country
• Sites: 1

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. Research has shown that boosting NAD+ bioavailability to stimulate SIRT-1, a "CR mimetic" approach, reduces CFPW and oxidative stress in old mice, and this lab recently took the first step in translating these findings in a study of adults with normal kidney function and elevated systolic blood pressure (SBP). The data 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. 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 is being proposed. It is hypothesized 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.

Conditions

Vascular Diseases; Kidney Disease; Blood Pressure; Oxidative Stress

Keywords

stiffness; chronic kidney disease; Hypertension

Outcome Measures

Primary Outcomes (1)

• carotid-femoral pulse wave velocity

  change in carotid-femoral pulse wave velocity

  Baseline and 3 months

Secondary Outcomes (2)

• Systolic blood pressure

  Baseline and 3 months

• Systolic blood pressure

  Baseline and 3 months

Other Outcomes (2)

• Number of participants with treatment-related adverse events as assessed by Common Terminology Criteria for Adverse Events v4.0

  weeks 2, 4, 6, 8, 10, and 12

• Change in blood cellular NAD+ metabolism

  baseline and 3 months

Study Arms (2)

Nicotinamide Riboside

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

Matched placebo capsules.

Drug: Nicotinamide riboside

Interventions

Nicotinamide riboside DRUG

Nicotinamide riboside is a naturally occurring vitamin B3 derivative found in yeast, bacteria, and mammalian tissues, and also has been detected in cows' milk.

Nicotinamide Riboside; Placebo

Eligibility Criteria

• Age: 35 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Colorado, Denver: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

UColorado

Aurora, Colorado, 80045, United States

RECRUITING

Related Publications (1)

• Oh ES, Opoku G, Darvish S, Craighead DH, Ostrow A, Rossman MJ, Steele CN, Struemph T, You Z, Seals DR, Chonchol M, Nowak KL. Sex Differences in Dementia and Mild Cognitive Impairment in Nondialysis CKD. Clin J Am Soc Nephrol. 2025 Nov 20. doi: 10.2215/CJN.0000000922. Online ahead of print. No abstract available.

  PMID: 41264372 DERIVED

MeSH Terms

Conditions

Vascular Diseases; Kidney Diseases; Renal Insufficiency, Chronic; Hypertension

Interventions

nicotinamide-beta-riboside

Condition Hierarchy (Ancestors)

Cardiovascular Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Renal Insufficiency; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Michel Chonchol, MD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Michel Chonchol, MD

CONTACT

303-724-7796; Michel.Chonchol@ucdenver.edu

Beverly Farmer, RN

CONTACT

303-724-7797; Beverly.Farmer@ucdenver.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 26, 2019
• First Posted: August 1, 2019
• Study Start: November 19, 2019
• Primary Completion: May 15, 2024
• Study Completion: September 15, 2024
• Last Updated: April 10, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)