Nicotinamide Mononucleotide in Patients Undergoing CABG Surgery
Purpose
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.
Condition
- Coronary Artery Bypass Graft
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- 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
- 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
Study Design
- Phase
- Phase 2
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental 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 |
|
|
Experimental 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 |
|
|
Placebo Comparator Placebo |
Placebo administered for 7 days preoperatively, on the day of surgery, and for 4 days postoperatively |
|
Recruiting Locations
Boston, Massachusetts 02115
More Details
- Status
- Recruiting
- Sponsor
- Brigham and Women's Hospital
Detailed 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.