Mechanistic Study of Nicotinamide Riboside on NAD+ Biology in Individuals With Combined Pulmonary Hypertension

NCT07563322 | Recruiting

• 2 other identifiers: 260020R01HL163960
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

Pulmonary hypertension (PH) is a serious condition that puts strain on the heart and lungs and often leads to frequent hospital stays and shortened life expectancy. The most common cause is heart disease affecting the left side of the heart. A particularly high-risk form, called combined pre- and post-capillary pulmonary hypertension (CPH), occurs in about one in four people with heart failure. There are currently no approved treatments for CPH, and many patients develop right-sided heart failure and die earlier than expected. This study is based on a new approach that uses advanced computer methods to analyze a patient's unique biology and identify potential drug targets. Using this method, we identified nicotinamide riboside (NR) as a promising option for people with CPH. NR is a form of vitamin B3 that helps the body make NAD⁺, a substance essential for how cells produce energy and stay healthy. NAD⁺ plays an important role in how heart and blood vessel cells function. Previous research in animals suggests NR may help improve blood vessel changes in the lungs and support heart function. NR has also shown potential benefits in human studies related to cell energy, mitochondrial health, and reducing oxidative stress. In this study, NR is used only as a dietary supplement that supports normal body processes, not as a proven treatment. The investigators will conduct a small, carefully controlled study in which participants receive NR and a placebo at different times. The goal is to understand how NR affects biological and biochemical markers in the body, not to test whether it improves symptoms or outcomes. Any clinical measurements are included only to help interpret the biological effects.

Conditions

Pulmonary Hypertension

Outcome Measures

Primary Outcomes (2)

• Biochemical: Change in NADH:Ubiquinone Oxidoreductase Subunit B7

  Baseline, Week 6, Week 9, Week 15

• Exploratory physiological measure: Change in 6-minute walk distance

  The 6MWT measures the distance (in meters), a participant can walk at a comfortable speed on a flat, hard surface in 6 minutes. The intent of the 6MWD test is to evaluate exercise capacity associated with carrying out daily physical activities.

  Baseline, Week 6, Week 9, Week 15

Secondary Outcomes (13)

• Change in N-terminal pro-B-type natriuretic peptide Values

  Baseline, Week 6, Week 9, Week 15

• Change in New York Heart Association Functional classification (NYHA)

  Baseline, Week 6, Week 9, Week 15

• Change in Empahsis-10 score

  Baseline, Week 6, Week 9, Week 15

• Change in SF-36 Score

  Baseline, Week 6, Week 9, Week 15

• Change in Minnesota Living with Heart Failure Questionnaire

  Baseline, Week 6, Week 9, Week 12

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Placebo portion of the trial

Drug: Placebo

Nicotinamide riboside (NR)

ACTIVE COMPARATOR

NR Portion of the trial

Dietary Supplement: Nicotinamide Riboside (NR)

Interventions

Nicotinamide Riboside (NR) DIETARY_SUPPLEMENT

Participants will be randomized to receive either 1000mg NR Daily or a placebo for 6 weeks, followed by a 3-week washout period. After this, they will receive the alternate treatment for an additional 6 weeks.

Nicotinamide riboside (NR)

Placebo DRUG

Participants will be randomized to receive either NR or a placebo for 6 weeks, followed by a 3-week washout period. After this, they will receive the alternate treatment for an additional 6 weeks.

Placebo

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged \>/= 18 to 85 years of age
• Diagnosis of Combined pre-/post-capillary PH (CPH) defined as mean pulmonary artery pressure \>20mmHg, pulmonary capillary wedge pressure \>15mmHg, and pulmonary vascular resistance ³3 Wood units
• NYHA Class I - III
• A qualifying Baseline RHC performed within 2 years of consent Clinical echocardiogram within the prior year with LVEF\>/= 45%
• Stable PH-specific and/or HF medication regimen and ≤1 diuretic adjustment within the three months prior to enrollment.
• Ambulatory - able to perform the walk test

You may not qualify if:

• Pulmonary hypertension due to congenital heart disease, connective tissue disease, or heritable pulmonary arterial hypertension
• Prohibited from regular activity due to wheelchair bound status, bed-bound status, reliance on a cane/walker, activity-limiting angina, activity-limiting osteoarthritis, or other conditions that limit activity
• Pregnancy
• Drug and toxin-associated PAH patients with active drug use
• Prior or active diagnosis of cirrhosis
• Active Malignancy
• Patients with evidence of moderate to severe hepatic impairment, defined as Child-Pugh Class B or C, or with alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels greater than 3 times the upper limit of normal (ULN), should be excluded
• eGFR by MDRD \<30mL/mi
• FEV1\< 60% predicted with more than mild abnormalities on lung imaging Current enrollment in or completion of any other investigational product study within 30 days of Screening.
• Hospitalization for any indication within 30 days of Day 1.
• History of severe allergic or anaphylactic reaction or hypersensitivity to NR
• No known mutation in NDUFB7

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37203, United States

RECRUITING

MeSH Terms

Conditions

Hypertension, Pulmonary

Interventions

nicotinamide-beta-riboside

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Evan L Brittain, MD

  VUMC

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Thomas E Strayer, PhD

CONTACT

615-936-0156; thomas.e.strayer@vumc.org

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Cardiovascular Medicine

Study Record Dates

• First Submitted: April 22, 2026
• First Posted: May 4, 2026
• Study Start: April 9, 2026
• Primary Completion (Estimated): April 30, 2027
• Study Completion (Estimated): July 30, 2027
• Last Updated: May 4, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

US (1)