Mechanistic Study of Nicotinamide Riboside on NAD+ Biology in Individuals With Combined Pulmonary Hypertension
28. dubna 2026 aktualizováno: 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.
Přehled studie
Postavení
Nábor
Podmínky
Intervence / Léčba
Typ studie
Intervenční
Zápis (Odhadovaný)
10
Fáze
- Nelze použít
Kontakty a umístění
Tato část poskytuje kontaktní údaje pro ty, kteří studii provádějí, a informace o tom, kde se tato studie provádí.
Studijní kontakt
- Jméno: Thomas E Strayer, PhD
- Telefonní číslo: 615-936-0156
- E-mail: thomas.e.strayer@vumc.org
Studijní místa
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Tennessee
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Nashville, Tennessee, Spojené státy, 37203
- Nábor
- Vanderbilt University Medical Center
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Vrchní vyšetřovatel:
- Evan L Brittain, MD
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Kontakt:
- Thomas E Strayer, PhD
- Telefonní číslo: 615-936-0156
- E-mail: thomas.e.strayer@vumc.org
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Kritéria účasti
Výzkumníci hledají lidi, kteří odpovídají určitému popisu, kterému se říká kritéria způsobilosti. Některé příklady těchto kritérií jsou celkový zdravotní stav osoby nebo předchozí léčba.
Kritéria způsobilosti
Věk způsobilý ke studiu
- Dospělý
- Starší dospělý
Přijímá zdravé dobrovolníky
Ne
Popis
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
Studijní plán
Tato část poskytuje podrobnosti o studijním plánu, včetně toho, jak je studie navržena a co studie měří.
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: Randomizované
- Intervenční model: Crossover Assignment
- Maskování: Dvojnásobek
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
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Komparátor placeba: 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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Aktivní komparátor: 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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Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
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Biochemical: Change in NADH:Ubiquinone Oxidoreductase Subunit B7
Časové okno: 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
Časové okno: 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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Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Change in N-terminal pro-B-type natriuretic peptide Values
Časové okno: 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)
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: Week 16
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Week 16
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Change in NAD+
Časové okno: 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.
Časové okno: 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
Časové okno: Baseline, 6-week, 9 week, 15 week
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Baseline, 6-week, 9 week, 15 week
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Spolupracovníci a vyšetřovatelé
Zde najdete lidi a organizace zapojené do této studie.
Spolupracovníci
Vyšetřovatelé
- Vrchní vyšetřovatel: Evan L Brittain, MD, VUMC
Termíny studijních záznamů
Tato data sledují průběh záznamů studie a předkládání souhrnných výsledků na ClinicalTrials.gov. Záznamy ze studií a hlášené výsledky jsou před zveřejněním na veřejné webové stránce přezkoumány Národní lékařskou knihovnou (NLM), aby se ujistily, že splňují specifické standardy kontroly kvality.
Hlavní termíny studia
Začátek studia (Aktuální)
9. dubna 2026
Primární dokončení (Odhadovaný)
30. dubna 2027
Dokončení studie (Odhadovaný)
30. července 2027
Termíny zápisu do studia
První předloženo
22. dubna 2026
První předloženo, které splnilo kritéria kontroly kvality
28. dubna 2026
První zveřejněno (Aktuální)
4. května 2026
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
4. května 2026
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
28. dubna 2026
Naposledy ověřeno
1. dubna 2026
Více informací
Termíny související s touto studií
Další relevantní podmínky MeSH
Další identifikační čísla studie
- 260020
- R01HL163960 (Grant/smlouva NIH USA)
Plán pro data jednotlivých účastníků (IPD)
Plánujete sdílet data jednotlivých účastníků (IPD)?
ANO
Popis plánu IPD
We will provide a data dictionary/dataset available upon reasonable request as needed.
Informace o lécích a zařízeních, studijní dokumenty
Studuje lékový produkt regulovaný americkým FDA
Ne
Studuje produkt zařízení regulovaný americkým úřadem FDA
Ne
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