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

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

Interventions

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.

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

  collaborator NIH

• University of Colorado, Denver

  lead OTHER

Principal Investigators

• Michel Chonchol, MD · University of Colorado, Denver

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

35 Years

Max Age

80 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2019-11-19

Primary Completion

2024-05-15

Completion

2024-09-15

FDA Drug

Yes

Countries

• United States

Study Locations