Nicotinamide Mononucleotide in Patients Undergoing CABG Surgery

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.

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