Nicotinamide Mononucleotide in Patients Undergoing CABG Surgery

Randomized Clinical Trial of β Nicotinamide Mononucleotide in Patients Undergoing CABG Surgery

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.

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:

1. Age ≥18 years

2. Scheduled to undergo elective isolated CABG surgery with cardiopulmonary bypass (CPB)

3. At increased risk of postoperative complications based on ≥1 of the following:

   1. Age ≥65 years
   2. eGFR <45 ml/min/1.73m2
   3. Documented history of congestive heart failure or left ventricular ejection fraction (LVEF) ≤40% within 6 months before surgery
   4. Diabetes mellitus and urine albumin-to-creatinine ratio >30 mg/g creatinine
   5. Peripheral arterial disease
   6. Anemia, defined as hemoglobin <10 g/dl
   7. Prior cardiac surgery

Exclusion Criteria:

1. Any of the following laboratory abnormalities at the time of screening:

   1. ALT >3-fold the upper limit of normal
   2. eGFR <30 ml/min/1.73m2 or ESKD on dialysis
   3. Hemoglobin <8 g/dl

2. History of gastric bypass or malabsorption

3. Active alcohol or illicit substance use in the prior 6 months

4. Participation in an investigational trial to evaluate pharmaceuticals or biologics within the past 3 months or 5 half-lives, whichever is shorter

5. Pregnant or breast-feeding

6. 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

7. Current use of niacin >100 mg/day or NMN, nicotinamide, or nicotinamide riboside at any dose

8. Conflict with other research studies

9. Any condition which, in the judgement of the investigator, might increase the risk to the participant