Safety and Tolerability of the Nutritional Supplement, Nicotinamide Riboside, in Systolic Heart Failure
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)
研究概览
简要总结
Mitochondrial dysfunction has been implicated in heart failure (HF), and is associated with an imbalance in intracellular ratio of reduced nicotinamide-adenine dinucleotide (NADH) to oxidized nicotinamide-adenine dinucleotide (NAD), or the NADH/NAD ratio. In mouse models of HF, we have found that normalization of the NADH/NAD, through supplementation with NAD+ precursors, is associated with improvement in cardiac function. This Study will randomize participants with systolic HF (ejection fraction ≤40%) to treatment with the NAD precursor, nicotinamide riboside (NR) or matching placebo, uptitrated to a final oral dose of 1000mg twice daily, to determine the safety and tolerability of NR in participants with systolic HF.
详细描述
Aim 1: Determine the safety and tolerability of NR in patients with clinically stable, systolic heart failure (LVEF <40%). To accomplish this Aim:
A) a total of 30 participants with clinically stable, systolic heart failure (LVEF <40%) will undergo 2:1 randomization to NR 250mg PO twice daily or matching placebo B) NR (or matching placebo), will be increased weekly by 250mg/dose (500mg/day) to a final dose of 1000mg PO twice daily. Clinic visits with labs bi-weekly during dose escalation will assess HF symptoms and monitor labs [B-type natriuretic peptide (BNP), complete blood count (CBC), glycosylated hemoglobin, alanine aminotransferase (ALT), creatine kinase (CK), insulin/glucose, uric acid, electrolytes, blood urea nitrogen (BUN) and creatinine (Cr).
C) to ensure intermediate-term safety and tolerability, participants will continue on their maximum tolerated dose (of NR or placebo) through Study Week 12
Aim 2: Determine whether, at the doses employed, NR and NAD are detectable in whole blood.
Aim 3 (Exploratory): Assess the range of potential effect sizes of NR on HF surrogate endpoints using:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
Randomization and dispensing of matching placebo will be performed by Investigational Drug Services at the University of Washington
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Men and women aged 18 and older with systolic heart failure [left ventricular ejection fraction (LVEF) by standard 2D echocardiography or radionuclide ventriculography of ≤40%] deemed, in the clinical opinion of their treating cardiologist to be non-ischemic or ischemic in origin.
- •Clinically stable (no cardiac procedures or hospitalizations for hospitalizations for cardiac causes, including HF, ischemia or arrhythmia) within the previous 3 months
- •Ability to undergo study procedures, including scheduled visits, blood draws and six-minute walk test (6MWT)
- •Willingness/ability to provide informed consent
排除标准
- •Heart failure with preserved ejection fraction (LVEF greater than 40%)
- •Heart failure due, in the opinion of their treating cardiologist, to etiologies other than non-ischemic or ischemic. Examples of exclusionary heart failure etiologies include primary valvular disease, or infiltrative or inflammatory cardiomyopathies.
- •Cardiac surgery, percutaneous coronary intervention (PCI) or cardiac device implantation within the previous 3 months
- •Hospitalizations for cardiovascular causes, including heart failure, chest pain, stroke, transient ischemic attack or arrhythmias within the previous 3 months
- •Inability to perform Study visits or procedures (e.g., physical inability to perform 6MWT)
- •Unwillingness/inability to provide informed consent
- •ALT greater than 3 times the upper limit of normal, hepatic insufficiency or active liver disease
- •Recent history of acute gout
- •Chronic renal insufficiency with creatinine ≥2.5mg/dL
- •Pregnant (or likely to become pregnant) women
- •Significant co-morbidity likely to cause death in the 6 month follow-up period
- •Significant active history of substance abuse within the previous 5 years
- •Current participation in another long-term clinical trial
- •History of intolerance to NR precursor compounds, including niacin or nicotinamide
研究组 & 干预措施
Nicotinamide Riboside
Nicotinamide riboside will be supplied as 250mg capsules, to be administered orally. The initial dose will be 1 capsule twice daily, followed by weekly up-titration by 1 capsule/dose to a final dose of 4 capsules (1000mg) twice daily at the end of Week 4. Participants will be continued on the final dose up to the final follow up visit (week 12). If, at any step, a dose increase is not tolerated, the maximum previously-tolerated dose will be continued through to week 12.
干预措施: nicotinamide riboside (Dietary Supplement)
Placebo
Matching placebo will be supplied as 250mg capsules, to be administered orally. The initial dose will be 1 capsule twice daily, followed by weekly up-titration by 1 capsule/dose to a final dose of 4 capsules (1000mg) twice daily at the end of Week 4. Participants will be continued on the final dose up to the final follow up visit (week 12). If, at any step, a dose increase is not tolerated, the maximum previously-tolerated dose will be continued through to week 12.
干预措施: Placebo (Drug)
结局指标
主要结局
Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)
时间窗: up to 12 weeks
Adverse Events
次要结局
- On-Trial Change in Whole Blood NAD+ Levels(Week 12-Week 0)
- Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment(16 weeks)
- Effect of NR on Change in Mitochondrial Function (Maximal Oxygen Consumption Rate)(Week 12 - Week 0)
研究者
Kevin O'Brien
Professor, Medicine/Cardiology
University of Washington