Nicotinamide Mmononucleotide in Patients Undergoing CABG Surgery

Mass General Brigham

Status and phase: Not yet enrolling; Phase 2

Conditions: Coronary Artery Bypass Graft

Treatments: Drug: MIB-626; Other: Placebo

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT07013591

1U01AG089040-01 (U.S. NIH Grant/Contract)

2025P000420

Details and patient eligibility

About

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.

Full 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.

Enrollment: 90 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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90 participants in 3 patient groups, including a placebo group

NMN (MIB-626) for 7 days preoperatively, on day of surgery, and for 4 days postoperatively

Experimental group

Description:

NMN (MIB-626) 1000 mg PO daily, for 7 days preoperatively, on day of surgery, and for 4 days postoperatively

Treatment:

Drug: MIB-626

NMN administered for 2 days preoperatively, on the day of surgery, and for 4 days postoperatively

Experimental group

Description:

NMN (MIB-626) 1,000 mg PO twice daily, administered for 2 days preoperatively, on the day of surgery, and for 4 days postoperatively

Treatment:

Drug: MIB-626

Placebo

Placebo Comparator group

Description:

Placebo administered for 7 days preoperatively, on the day of surgery, and for 4 days postoperatively

Treatment:

Other: Placebo