The investigators will perform a phase 2a, randomized, double-blind, placebo-controlled clinical trial in adult patients undergoing elective cardiac 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 cardiac 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 3 days postoperatively Arm B: NMN 1,000 mg PO twice daily, administered for 2 days preoperatively, on the day of surgery, and for 3 days postoperatively Arm C: Placebo PO twice daily, administered for 7 days preoperatively, on the day of surgery, and for 3 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 Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
90
Brigham and Women's Hospital
Boston, Massachusetts, United States
RECRUITINGNAD+ concentration in the myocardial tissue
NAD+ concentration in the myocardial tissue (right atrial appendage) obtained intraoperatively, measured using the validated NADome Quant assay
Time frame: Intraoperatively (single time point)
Intracellular levels of NAD+ and related metabolites
NAD+, NADH, and related metabolite concentrations in discarded tissue collected intraoperatively, including right atrial appendage, internal mammary artery, sternal muscle, and fat
Time frame: Intraoperatively (single time point)
Circulating levels of NAD+ and related metabolites
NAD+, NADH, and related metabolite concentrations in the circulation and in peripheral blood mononuclear cells
Time frame: Baseline to day 90
Markers of cardiac injury/dysfunction
Circulating levels of cardiac troponin I, creatine kinase MB fraction (CKMB), and N-terminal pro-B-type natriuretic peptide (NT-pro-BNP)
Time frame: Preoperatively, on ICU arrival, and on postoperative days 1-4
Acute kidney injury (AKI)
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
Time frame: 7 days post-operatively
Serum creatinine (SCr)
Maximum baseline-adjusted changes in SCr
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Time frame: Immediately pre-operative to 7 days post-operative
Cystatin C
Circulating levels of cystatin C
Time frame: Preoperatively, on ICU arrival, and on postoperative days 1-4
Neutrophil gelatinase-associated lipocalin (NGAL)
Circulating levels of measured neutrophil gelatinase-associated lipocalin (NGAL)
Time frame: Preoperatively, on ICU arrival, and on postoperative days 1-4
Kidney Injury Molecule-1 (KIM-1)
Circulating levels of KIM-1
Time frame: Preoperatively, on ICU arrival, and on postoperative days 1-4
NMN level
Plasma concentrations of NMN
Time frame: Preoperatively, on ICU arrival, and on postoperative days 1-4
2PY Level
Plasma concentrations of 2PY
Time frame: Preoperatively, on ICU arrival, and on postoperative days 1-4
N-Methylnicotinamide level
Plasma N-methylynicotinamide level
Time frame: Preoperatively, on ICU arrival, and on postoperative days 1-4
nicotinamide level
Plasma nicotinamide concentrations
Time frame: Preoperatively, on ICU arrival, and on postoperative days 1-4