Pilot Study of Preoperative Nicotinamide Riboside (Vitamin B3) Supplementation in Patients Undergoing Elective Left Ventricular Assist Device (LVAD) Implantation
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 入组人数
- 5
- 试验地点
- 2
- 主要终点
- Number of Participates Experiencing Treatment-Emergent Adverse Events (Safety and Tolerability)
研究概览
简要总结
While preliminary data show that oral nicotinamide riboside (NR) supplementation increases myocardial levels of oxidized nicotine-adenine dinucleotide (NAD+) levels in mice, there has been no direct evidence that suggests oral NR increases NAD+ levels or improves mitochondrial function in human hearts. This Pilot Study is designed to obtain feasibility data for a planned, larger study testing the hypothesis that oral NR supplementation will increase myocardial NAD+ levels and improve cardiomyocyte mitochondrial function in participants with advanced heart failure planned for elective left ventricular assist device (LVAD) implantation. To demonstrate safety and feasibility of NR in this patient population, the investigators propose to enroll 5 participants planned for LVAD implantation in a Pilot Study of NR in which participants will receive NR, up-titrated over 3 days to a final NR dose of 1000mg twice daily. Blood and myocardial tissue analyses collected previously from age- and gender-matched LVAD recipients will serve as controls.
详细描述
This Pilot Study will examine the following Aims:
Aim 1: Enroll 5 participants scheduled for elective left ventricular assist device (LVAD) placement into an open-label study of nicotinamide riboside (NR).
a. Participants will have labs (including safety panels) drawn at baseline (Day 1), then receive escalating doses of NR to a maximum dose of 1000mg twice daily by Day 3. Participants will be continued on NR at 1000mg twice daily until LVAD implantation surgery.
On the morning of LVAD implantation Surgery (Day 5 or later), participants will have final labs drawn. Samples of fresh cardiac tissue removed from the left ventricular apex during LVAD implantation surgery will be collected in the operating room. The primary analyses will be performed on NR-treated participants who were on the maximum NR dose of 1000mg twice daily for at least 2 days prior to LVAD implantation surgery. The maximum duration of NR administration will be capped at 14 days. If the surgery doesn't happen by then, the participant will be withdrawn from the study.
Aim 2: Determine the effect of NR (as compared to historical controls) on levels of the oxidized and reduced forms of nicotine-adenine dinucleotide (NAD+ and NADH, respectively), mitochondrial function and its regulation through modifications of the epigenome in the failing myocardium.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
盲法说明
Study biostatistician will be blinded to group (NR vs. untreated controls)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of advanced heart failure.
- •Planned elective LVAD implantation surgery with patient agreements for candidacy in place as required by UWMC.
- •Hospital inpatient at time of enrollment.
- •Ability to undergo Study procedures.
- •Willingness/ability to provide informed consent.
排除标准
- •Current smoking
- •Receiving certain concurrent supplements (to be determined at discretion of the PI). Note that UWMC Nutrition Care standards call for a general multivitamin (1 tab PO daily) as part of the advanced heart failure therapy (AHFT) work-up.
- •Known allergies to niacin or nicotinamide.
- •Hepatic, renal, endocrine, or neurological disease that disqualify them from consideration for LVAD implantation.
- •Inability to perform Study visits or procedures.
- •Unwillingness/inability to provide informed consent.
- •Women who are currently pregnant or who wish to become pregnant over the course of the study follow-up are not allowed to join this study. This exclusion is built into the LVAD candidate selection process.
结局指标
主要结局
Number of Participates Experiencing Treatment-Emergent Adverse Events (Safety and Tolerability)
时间窗: from Day 1 receiving NR to the day before LVAD surgery (between Day 6-Day 14)
Participants experiencing adverse events during the time they are on the study drug. Regarding time frame: Day 1 is the first day that the study subjects start taking the study drug (NR). The participants stop taking the study drug on the day before his/her LVAD surgery (between Days 6 and 14).
Pre/Post NR Comparison of Maximal Mitochondrial Respiration in PBMCs
时间窗: from Day 1 receiving NR to the day before LVAD surgery (between Day 6-Day 14)
Comparison of maximal mitochondrial respiration in PBMCs on the Day of LVAD Surgery Pre- vs Post-NR Administration
次要结局
- Effect of NR on Whole Blood NAD+ Levels(from Day 1 receiving NR to the day before LVAD surgery (between Day 6-Day 14))
- Between-group Comparison of Mitochondrial Respiration (Seahorse Assay) in Isolated Peripheral Blood Mononuclear Cells (PBMCs)(Data collected 6-14 days after study intervention (oral NR) has been initiated.)
- Between-group Comparison of Whole Blood NAD+ Levels(Data collected 6-14 days after study intervention (oral NR) has been initiated.)
研究者
Kevin O'Brien
Professor, School of Medicine: Department of Medicine: Cardiology: Clinical
University of Washington