Nicotinamide Mmononucleotide in Patients Undergoing CABG Surgery

Phase 2

Not yet recruiting

• Conditions: Coronary Artery Bypass Graft
• Interventions: Drug: MIB-626; Other: Placebo

• Registration Number: NCT07013591
• Lead Sponsor: Brigham and Women's Hospital

Brief Summary

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.

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.

Study Timeline

• Study First Submitted: 2025-05-09
• Status Verified: 2025-06
• Study First Submitted QC: 2025-06-02
• Last Update Submitted: 2025-06-02
• Study First Posted: 2025-06-10
• Last Update Posted: 2025-06-10
• Study Start: 2025-10-01
• Primary Completion: 2028-10-01
• Study Completion: 2029-01-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 90

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
NMN (MIB-626) for 7 days preoperatively, on day of surgery, and for 4 days postoperatively	MIB-626	NMN (MIB-626) 1000 mg PO daily, for 7 days preoperatively, on day of surgery, and for 4 days postoperatively
NMN administered for 2 days preoperatively, on the day of surgery, and for 4 days postoperatively	MIB-626	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	Placebo	Placebo administered for 7 days preoperatively, on the day of surgery, and for 4 days postoperatively

Primary Outcome Measures

Name	Time	Method
NAD+ concentration in the myocardial tissue	Intraoperatively (single time point)	NAD+ concentration in the myocardial tissue (right atrial appendage) obtained intraoperatively, measured using the validated NADome Quant assay

Secondary Outcome Measures

Name	Time	Method
Intracellular levels of NAD+ and related metabolites	Intraoperatively (single time point)	NAD+, NADH, and related metabolite concentrations in discarded tissue collected intraoperatively, including right atrial appendage, internal mammary artery, sternal muscle, and fat
Circulating levels of NAD+ and related metabolites	Baseline to day 90	NAD+, NADH, and related metabolite concentrations in the circulation and in peripheral blood mononuclear cells
Markers of cardiac injury/dysfunction	Preoperatively, on ICU arrival, and on postoperative days 1-4	Circulating levels of cardiac troponin I, creatine kinase MB fraction (CKMB), and N-terminal pro-B-type natriuretic peptide (NT-pro-BNP)
Acute kidney injury (AKI)	7 days post-operatively	Incidence of acute kidney injury (AKI) defined according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria as any of the following: 1) urine output \<0.5 ml/kg/h for ≥6 consecutive hours (assessed within the first 48h or until the Foley catheter is removed, whichever occurs first); 2) an increase in SCr ≥0.3 mg/dl within the first 48h; 3) an increase in SCr ≥50% within the first 7 days; or 4) receipt of KRT within the first 7 days
Serum creatinine (SCr)	Immediately pre-operative to 7 days post-operative	Maximum baseline-adjusted changes in SCr
Cystatin C	Preoperatively, on ICU arrival, and on postoperative days 1-4	Circulating levels of cystatin C
Neutrophil gelatinase-associated lipocalin (NGAL)	Preoperatively, on ICU arrival, and on postoperative days 1-4	Circulating levels of measured neutrophil gelatinase-associated lipocalin (NGAL)
Kidney Injury Molecule-1 (KIM-1)	Preoperatively, on ICU arrival, and on postoperative days 1-4	Circulating levels of KIM-1
NMN level	Preoperatively, on ICU arrival, and on postoperative days 1-4	Plasma concentrations of NMN
2PY Level	Preoperatively, on ICU arrival, and on postoperative days 1-4	Plasma concentrations of 2PY
N-Methylnicotinamide level	Preoperatively, on ICU arrival, and on postoperative days 1-4	Plasma N-methylynicotinamide level
nicotinamide level	Preoperatively, on ICU arrival, and on postoperative days 1-4	Plasma nicotinamide concentrations

Trial Locations

Locations (1)

Brigham and Women's Hospital; 🇺🇸 Boston, Massachusetts, United States