Randomized Clinical Trial of β Nicotinamide Mononucleotide in Patients Undergoing CABG Surgery
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 90
- 试验地点
- 1
- 主要终点
- NAD+ concentration in the myocardial tissue
研究概览
简要总结
The investigators will perform a phase 2a, randomized, double-blind, placebo-controlled clinical trial in adult patients undergoing elective coronary artery bypass grafting (CABG) surgery to investigate the effects of oral nicotinamide mononucleotide (NMN) administration on myocardial NAD+ concentrations and on postoperative markers of myocardial and kidney injury.
详细描述
This is a phase 2a, randomized, double-blind, parallel-group, placebo-controlled clinical trial in adult patients undergoing elective coronary artery bypass grafting (CABG) surgery. A total of 90 patients will be randomized 1:1:1 to placebo or to one of two dosing regimens of NMN seven days prior to surgery as follows:
Arm A: NMN 1,000 mg PO twice daily, administered for 7 days preoperatively, on the day of surgery, and for 4 days postoperatively
Arm B: NMN 1,000 mg PO twice daily, administered for 2 days preoperatively, on the day of surgery, and for 4 days postoperatively
Arm C: Placebo PO twice daily, administered for 7 days preoperatively, on the day of surgery, and for 4 days postoperatively
There are two major study aims:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Age ≥18 years
- •Scheduled to undergo elective isolated CABG surgery with cardiopulmonary bypass (CPB)
- •At increased risk of postoperative complications based on ≥1 of the following:
- •Age ≥65 years
- •eGFR <45 ml/min/1.73m2
- •Documented history of congestive heart failure or left ventricular ejection fraction (LVEF) ≤40% within 6 months before surgery
- •Diabetes mellitus and urine albumin-to-creatinine ratio >30 mg/g creatinine
- •Peripheral arterial disease
- •Anemia, defined as hemoglobin <10 g/dl
- •Prior cardiac surgery
排除标准
- •Any of the following laboratory abnormalities at the time of screening:
- •ALT >3-fold the upper limit of normal
- •eGFR <30 ml/min/1.73m2 or ESKD on dialysis
- •Hemoglobin <8 g/dl
- •History of gastric bypass or malabsorption
- •Active alcohol or illicit substance use in the prior 6 months
- •Participation in an investigational trial to evaluate pharmaceuticals or biologics within the past 3 months or 5 half-lives, whichever is shorter
- •Pregnant or breast-feeding
- •Unwillingness to use contraception while taking study drug and for 8 weeks after the last dose for women of reproductive age or non-sterilized male participants who are sexually active with a female partner of childbearing potential
- •Current use of niacin >100 mg/day or NMN, nicotinamide, or nicotinamide riboside at any dose
- •Conflict with other research studies
- •Any condition which, in the judgement of the investigator, might increase the risk to the participant
研究组 & 干预措施
NMN (MIB-626) for 7 days preoperatively, on day of surgery, and for 4 days postoperatively
NMN (MIB-626) 1000 mg PO daily, for 7 days preoperatively, on day of surgery, and for 4 days postoperatively
干预措施: MIB-626 (Drug)
NMN administered for 2 days preoperatively, on the day of surgery, and for 4 days postoperatively
NMN (MIB-626) 1,000 mg PO twice daily, administered for 2 days preoperatively, on the day of surgery, and for 4 days postoperatively
干预措施: MIB-626 (Drug)
Placebo
Placebo administered for 7 days preoperatively, on the day of surgery, and for 4 days postoperatively
干预措施: Placebo (Other)
结局指标
主要结局
NAD+ concentration in the myocardial tissue
时间窗: Intraoperatively (single time point)
NAD+ concentration in the myocardial tissue (right atrial appendage) obtained intraoperatively, measured using the validated NADome Quant assay
次要结局
- Intracellular levels of NAD+ and related metabolites(Intraoperatively (single time point))
- Circulating levels of NAD+ and related metabolites(Baseline to day 90)
- Markers of cardiac injury/dysfunction(Preoperatively, on ICU arrival, and on postoperative days 1-4)
- Acute kidney injury (AKI)(7 days post-operatively)
- Cystatin C(Preoperatively, on ICU arrival, and on postoperative days 1-4)
- Serum creatinine (SCr)(Immediately pre-operative to 7 days post-operative)
- Neutrophil gelatinase-associated lipocalin (NGAL)(Preoperatively, on ICU arrival, and on postoperative days 1-4)
- Kidney Injury Molecule-1 (KIM-1)(Preoperatively, on ICU arrival, and on postoperative days 1-4)
- NMN level(Preoperatively, on ICU arrival, and on postoperative days 1-4)
- 2PY Level(Preoperatively, on ICU arrival, and on postoperative days 1-4)
- N-Methylnicotinamide level(Preoperatively, on ICU arrival, and on postoperative days 1-4)
- nicotinamide level(Preoperatively, on ICU arrival, and on postoperative days 1-4)
研究者
Shalendar Bhasin, MD
Principal Investigator
Brigham and Women's Hospital