Mechanistic Study of Nicotinamide Riboside on NAD+ Biology in Individuals With Combined Pulmonary Hypertension
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Biochemical: Change in NADH:Ubiquinone Oxidoreductase Subunit B7
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
- •History of severe allergic or anaphylactic reaction or hypersensitivity to NR
- •No known mutation in NDUFB7
研究组 & 干预措施
Placebo
Placebo portion of the trial
干预措施: Placebo (Drug)
Nicotinamide riboside (NR)
NR Portion of the trial
干预措施: Nicotinamide Riboside (NR) (Dietary Supplement)
结局指标
主要结局
Biochemical: Change in NADH:Ubiquinone Oxidoreductase Subunit B7
时间窗: Baseline, Week 6, Week 9, Week 15
Exploratory physiological measure: Change in 6-minute walk distance
时间窗: Baseline, Week 6, Week 9, Week 15
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.
次要结局
- 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)
- Change in Tricuspid annular plane systolic excursion(Baseline, Week 6, Week 9, Week 15)
- Change in RV Fractional Area(Baseline, Week 6, Week 9, Week 15)
- Change in RV Longitudinal Strain(Baseline, Week 6, Week 9, Week 15)
- Incidence of Treatment-Emergent Adverse Event(Baseline, Week 6, Week 9, Week 15)
- Number of patients with an incidence of death(Week 16)
- Change in NAD+(Baseline, 6-weeks, 9-weeks, 12-weeks)
- ,Change in NADH.(Baseline, 6-week, 9-week, 12-week)
- Change in Nicotinamide Mononucleotide(Baseline, 6-week, 9 week, 15 week)
研究者
Evan Brittain
Professor, Cardiovascular Medicine
Vanderbilt University Medical Center