Nicotinamide Riboside for Kidney Disease

Recruiting in Palo Alto (17 mi)

Overseen byMichel Chonchol, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: University of Colorado, Denver

Prior Safety Data

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?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.

Eligibility Criteria

This trial is for adults aged 35-80 with moderate to severe chronic kidney disease (stages III or IV), who have had stable weight and blood pressure control. They must not be pregnant, planning pregnancy, or nursing, and should not have been hospitalized recently or taking certain immunosuppressants.

Inclusion Criteria

My kidney function is moderately to severely reduced but stable.

Ability to provide informed consent

My weight has been stable, with less than a 2 kg change, for the last 3 months.

+4 more

Exclusion Criteria

I am pregnant, nursing, or planning to become pregnant.

I am on chronic dialysis for advanced kidney disease.

I have not taken immunosuppressants like cyclosporine or steroids in the past year.

+6 more

Participant Groups

The trial tests if nicotinamide riboside supplements can reduce arterial stiffness and high systolic blood pressure in CKD patients. It's a phase IIa study where participants are randomly given either the supplement or a placebo twice daily for three months.

2Treatment groups

Experimental Treatment

Placebo Group

Group I: Nicotinamide RibosideExperimental Treatment1 Intervention

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.

Group II: PlaceboPlacebo Group1 Intervention

Matched placebo capsules.

Nicotinamide Riboside is already approved in United States, European Union for the following indications:

🇺🇸 Approved in United States as Niagen for: