Overview
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.
Description
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:
Aim 1: Test the effect of oral NMN administration on myocardial NAD+ concentration.
Aim 2: Test the effect of oral NMN administration on postoperative myocardial and kidney injury parameters.
Eligibility
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
