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

• Status: Recruiting
• Trial end date: 2024-09-15
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Colorado, Denver
• Collaborator: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Treatments: Niacin; Niacinamide; Nicotinic Acids

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.