Mechanistic Study of Nicotinamide Riboside on NAD+ Biology in Individuals With Combined Pulmonary Hypertension
28 aprile 2026 aggiornato da: Evan Brittain, Vanderbilt University Medical Center
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.
Panoramica dello studio
Stato
Reclutamento
Condizioni
Intervento / Trattamento
Tipo di studio
Interventistico
Iscrizione (Stimato)
10
Fase
- Non applicabile
Contatti e Sedi
Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.
Contatto studio
- Nome: Thomas E Strayer, PhD
- Numero di telefono: 615-936-0156
- Email: thomas.e.strayer@vumc.org
Luoghi di studio
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Tennessee
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Nashville, Tennessee, Stati Uniti, 37203
- Reclutamento
- Vanderbilt University Medical Center
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Investigatore principale:
- Evan L Brittain, MD
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Contatto:
- Thomas E Strayer, PhD
- Numero di telefono: 615-936-0156
- Email: thomas.e.strayer@vumc.org
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Criteri di partecipazione
I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.
Criteri di ammissibilità
Età idonea allo studio
- Adulto
- Adulto più anziano
Accetta volontari sani
No
Descrizione
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
Piano di studio
Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: Randomizzato
- Modello interventistico: Assegnazione incrociata
- Mascheramento: Doppio
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
|---|---|
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Comparatore placebo: Placebo
Placebo portion of the trial
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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.
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Comparatore attivo: Nicotinamide riboside (NR)
NR Portion of the trial
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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.
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Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
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Biochemical: Change in NADH:Ubiquinone Oxidoreductase Subunit B7
Lasso di tempo: Baseline, Week 6, Week 9, Week 15
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Baseline, Week 6, Week 9, Week 15
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Exploratory physiological measure: Change in 6-minute walk distance
Lasso di tempo: Baseline, Week 6, Week 9, Week 15
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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.
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Baseline, Week 6, Week 9, Week 15
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Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
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Change in N-terminal pro-B-type natriuretic peptide Values
Lasso di tempo: Baseline, Week 6, Week 9, Week 15
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Baseline, Week 6, Week 9, Week 15
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Change in New York Heart Association Functional classification (NYHA)
Lasso di tempo: Baseline, Week 6, Week 9, Week 15
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The New York Heart Association (NYHA) functional classification is a widely used system for assessing the severity of heart failure based on symptoms and their impact on physical activity.
It is divided into four classes: Class I includes individuals with no limitations on physical activity and no symptoms during ordinary activities; Class II includes individuals with mild limitations on physical activity, where ordinary physical activity causes fatigue, shortness of breath, or other symptoms; Class III includes individuals with marked limitations on physical activity, where less-than-ordinary activity results in symptoms; and Class IV includes individuals who are unable to engage in any physical activity without discomfort and may experience symptoms even at rest.
The NYHA functional class will be evaluated at Baseline and Visit 2. The NYHA functional classification is an ordinal scale ranging from Class I to Class IV, with lower class numbers indicating better functional status.
Imp
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Baseline, Week 6, Week 9, Week 15
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Change in Empahsis-10 score
Lasso di tempo: Baseline, Week 6, Week 9, Week 15
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The emPHasis-10 is a short and easy questionnaire that consists of 10 items that address breathlessness, fatigue, control, and confidence.
Each item is scored on a semantic differential six-point scale (0-5), with contrasting adjectives at each end.
A total emPHasis-10 score is derived using simple aggregation of the 10 items.
emPHasis-10 scores range from 0 to 50, higher scores indicate worse quality of life
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Baseline, Week 6, Week 9, Week 15
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Change in SF-36 Score
Lasso di tempo: Baseline, Week 6, Week 9, Week 15
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The SF36 includes one multi-item scale that assesses eight health concepts: 1) limitations in physical activities because of health problems; 2) limitations in social activities because of physical and emotional problems; 3) limitations in usual role activities because of physical health problems; 4) bodily pain; 5) general mental health (psychological distress and well-being); 6) limitations in usual role activities because of emotional problems; 7) vitality (energy and fatigue); and 8) general health perceptions.
Remote subjects will complete the SF-36 at baseline and each subsequent visit during the study.
Each SF-36 domain is scored using a standardized transformation to a 0-100 scale, with higher scores indicating better health status (i.e., fewer limitations, less pain, greater well-being, and higher vitality).
Improvements over time are reflected by increases in domain scores relative to baseline.
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Baseline, Week 6, Week 9, Week 15
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Change in Minnesota Living with Heart Failure Questionnaire
Lasso di tempo: Baseline, Week 6, Week 9, Week 12
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The MLHF (Minnesota Living with Heart Failure Questionnaire) is a widely used disease-specific instrument designed to assess the impact of heart failure on an individual's quality of life.
The MLHF includes 21 items that evaluate various aspects of physical, emotional, and social functioning as affected by heart failure.
It focuses on areas such as 1) physical limitations due to heart failure symptoms; 2) the emotional impact of living with heart failure; 3) interference with social activities; 4) effects on usual daily activities; and 5) overall quality of life as perceived by the patient.
Participants will complete the MLHF at baseline and during each subsequent visit to monitor changes in their quality of life throughout the study.
Each MLHF item is scored on a 6-point Likert scale ranging from 0 ("no impact") to 5 ("very much"), reflecting how much heart failure has affected the patient during the past month.
Item scores are summed to produce a total score ranging from 0 to 105, w
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Baseline, Week 6, Week 9, Week 12
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Change in Tricuspid annular plane systolic excursion
Lasso di tempo: Baseline, Week 6, Week 9, Week 15
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Baseline, Week 6, Week 9, Week 15
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Change in RV Fractional Area
Lasso di tempo: Baseline, Week 6, Week 9, Week 15
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Right ventricular fractional area change (RV FAC) is a non-invasive measure of right ventricular systolic function assessed using transthoracic echocardiography.
RV FAC is calculated from standard echocardiographic images by comparing right ventricular area during diastole and systole.
Higher RV FAC values indicate better right ventricular function.
Change in RV FAC from baseline will be used to assess changes in right ventricular systolic performance during the study.
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Baseline, Week 6, Week 9, Week 15
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Change in RV Longitudinal Strain
Lasso di tempo: Baseline, Week 6, Week 9, Week 15
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Right ventricular longitudinal strain is a non-invasive measure of right ventricular myocardial function assessed using transthoracic echocardiography with strain analysis.
RV longitudinal strain quantifies myocardial deformation of the right ventricle during systole.
More negative strain values indicate better right ventricular systolic function.
Change in RV longitudinal strain from baseline will be used to assess changes in right ventricular myocardial performance during the study.
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Baseline, Week 6, Week 9, Week 15
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Incidence of Treatment-Emergent Adverse Event
Lasso di tempo: Baseline, Week 6, Week 9, Week 15
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This will be a measure of adverse events in the study
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Baseline, Week 6, Week 9, Week 15
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Number of patients with an incidence of death
Lasso di tempo: Week 16
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Week 16
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Change in NAD+
Lasso di tempo: Baseline, 6-weeks, 9-weeks, 12-weeks
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Baseline, 6-weeks, 9-weeks, 12-weeks
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,Change in NADH.
Lasso di tempo: Baseline, 6-week, 9-week, 12-week
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Baseline, 6-week, 9-week, 12-week
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Change in Nicotinamide Mononucleotide
Lasso di tempo: Baseline, 6-week, 9 week, 15 week
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Baseline, 6-week, 9 week, 15 week
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Collaboratori e investigatori
Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.
Collaboratori
Investigatori
- Investigatore principale: Evan L Brittain, MD, VUmc
Studiare le date dei record
Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.
Studia le date principali
Inizio studio (Effettivo)
9 aprile 2026
Completamento primario (Stimato)
30 aprile 2027
Completamento dello studio (Stimato)
30 luglio 2027
Date di iscrizione allo studio
Primo inviato
22 aprile 2026
Primo inviato che soddisfa i criteri di controllo qualità
28 aprile 2026
Primo Inserito (Effettivo)
4 maggio 2026
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
4 maggio 2026
Ultimo aggiornamento inviato che soddisfa i criteri QC
28 aprile 2026
Ultimo verificato
1 aprile 2026
Maggiori informazioni
Termini relativi a questo studio
Termini MeSH pertinenti aggiuntivi
Altri numeri di identificazione dello studio
- 260020
- R01HL163960 (Sovvenzione/contratto NIH degli Stati Uniti)
Piano per i dati dei singoli partecipanti (IPD)
Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?
SÌ
Descrizione del piano IPD
We will provide a data dictionary/dataset available upon reasonable request as needed.
Informazioni su farmaci e dispositivi, documenti di studio
Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti
No
Studia un dispositivo regolamentato dalla FDA degli Stati Uniti
No
Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .