Nicotinamide Riboside Supplementation for Treating Elevated Systolic Blood Pressure and Arterial Stiffness in Middle-aged and Older Adults

Study Overview: This is a randomized, double-blind, placebo-controlled, parallel design, single site phase IIa clinical trial assessing the efficacy of nicotinamide riboside supplementation to lower systolic blood pressure (SBP) and aortic stiffness in middle-aged to older (MA/O) adults (50-79 years) with elevated to stage-1 systolic hypertension (SBP: 120-139 mmHg). Nicotinamide riboside is an endogenously occurring precursor of NAD+ and a novel caloric restriction mimetic in humans that is now commercially available as a dietary ingredient/supplement. We have recently demonstrated that chronic supplementation with nicotinamide riboside lowers SBP and carotid-femoral pulse wave velocity (CFPWV; gold-standard measure of aortic stiffness and independent risk factor for cardiovascular diseases) in a small pilot study of healthy MA/O adults; the greatest reductions in SBP were observed in a subgroup with baseline SBP in the elevated/stage-1 hypertension range. As a next translational step, the present study proposes to assess the efficacy of 3 months of nicotinamide riboside supplementation for decreasing SBP (primary outcome) and aortic stiffness (secondary outcome) in a larger cohort of MA/O men and women with SBP in the elevated/stage-1 hypertension range. As secondary aims, we will also assess safety and tolerability of long-term nicotinamide riboside supplementation, and the effects of nicotinamide riboside supplementation vs. placebo on NAD+ metabolites and circulating biomarkers of vasoconstriction, oxidative stress and inflammation.

Subject Enrollment and Screening: Potential participants will be made aware of the proposed study through described recruitment efforts (see Recruitment and Retention section). Interested participants will contact a staff research assistant via phone or email (contact information supplied with recruitment materials) and will complete a general screening form online through the Research Electronic Data Capture (REDCap) system to determine eligibility. REDCap is a secure web-based application designed to support data capture for research studies.

After hearing a thorough study description and having all questions answered by the staff research assistant, those eligible and interested in participating in the study will provide written and verbal informed consent, and undergo in-person screening at the CU Boulder Clinical Translational Research Center (CTRC). Informed consent will only be obtained by members of the research team who have been observed and approved by the CTRC Research Subject Advocate (see Protection of Human Subjects). We plan to consent 148 subjects in order to meet our enrollment targets (to account for an ~25% rate of exclusion base on in-person screening).

In-person screening will include: review of medical history; physical exam; resting heart rate; resting blood pressure; blood draw for metabolic profile, lipid profile, complete blood count, and thyroid stimulating hormone; measurement of ankle-brachial index; and a 12-lead ECG at rest and during graded exercise testing (see the Eligibility Criteria section for detailed inclusion/exclusion criteria).

Resting blood pressure will be measured on a second occasion within one week of the initial screening to establish baseline blood pressure status; SBP measured on the two separate days will be averaged and must be in the elevated to stage-1 hypertension range (120-139 mmHg) for enrollment into the study.