Clinical trial NCT07013591: Nicotinamide Mmononucleotide in Patients Undergoing CABG Surgery
Official title: Randomized Clinical Trial of β Nicotinamide Mononucleotide in Patients Undergoing CABG Surgery
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Coronary Artery Bypass Graft
Keywords: coronary artery bypass graft
cardiac surgery
cardiopulmonary bypass
nicotinamide
NMN
acute kidney injury
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
Collaborators: name: National Institute on Aging (NIA)
First posted: 2025-06-10
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: NAD+ concentration in the myocardial tissue
timeFrame: Intraoperatively (single time point)
Secondary outcomes:
measure: Intracellular levels of NAD+ and related metabolites
timeFrame: Intraoperatively (single time point)
measure: Circulating levels of NAD+ and related metabolites
timeFrame: Baseline to day 90
measure: Markers of cardiac injury/dysfunction
timeFrame: Preoperatively, on ICU arrival, and on postoperative days 1-4
measure: Acute kidney injury (AKI)
timeFrame: 7 days post-operatively
measure: Serum creatinine (SCr)
timeFrame: Immediately pre-operative to 7 days post-operative
measure: Cystatin C
timeFrame: Preoperatively, on ICU arrival, and on postoperative days 1-4
measure: Neutrophil gelatinase-associated lipocalin (NGAL)
timeFrame: Preoperatively, on ICU arrival, and on postoperative days 1-4
measure: Kidney Injury Molecule-1 (KIM-1)
timeFrame: Preoperatively, on ICU arrival, and on postoperative days 1-4
measure: NMN level
timeFrame: Preoperatively, on ICU arrival, and on postoperative days 1-4
measure: 2PY Level
timeFrame: Preoperatively, on ICU arrival, and on postoperative days 1-4
measure: N-Methylnicotinamide level
timeFrame: Preoperatively, on ICU arrival, and on postoperative days 1-4
measure: nicotinamide level
timeFrame: Preoperatively, on ICU arrival, and on postoperative days 1-4
Other outcomes:
measure: Left ventricular ejection fraction (LVEF)
timeFrame: change from immediately preoperative to immediate postoperative
measure: Atrial fibrillation
timeFrame: First seven days postoperatively
measure: Vasoactive-inotropic score
timeFrame: Immediately preoperatively to 24-hours post-incision
measure: Time-to-liberation from vasoactive medications
timeFrame: End of cardiopulmonary bypass to 24 hours post surgery
measure: ICU length of stay
timeFrame: Time in days in the ICU post-operatively, from the day of admission to the ICU postoperatively after the coronary artery bypass surgery to the time of release from ICU or date of death from any cause, up to 90 days
Locations:
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
Study officials:
affiliation: Brigham and Women's Hosptial
name: Shalender Bhasin, MB, BS
role: PRINCIPAL_INVESTIGATOR
References: