Nicotinamide Mononucleotide in Patients Undergoing Cardiac Surgery

ConditionCardiac Surgery

Trial statusRecruiting

Trial phasePhase 2

Trial typeInterventional

Biological sexAll

Age18+

SponsorBrigham and Women's Hospital

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Age ≥18 years

Scheduled to undergo elective isolated CABG surgery and/or valve surgery with cardiopulmonary bypass (CPB)

Age ≥65 years

eGFR <45 ml/min/1.73m2

Disqualifiers

ALT >3-fold the upper limit of normal

eGFR <30 ml/min/1.73m2 or ESKD on dialysis

Hemoglobin <8 g/dl

History of malabsorption

Trial design

Design model

Parallel

Treatments tested in this trial

MIB-626
Drug
An orally-administered stable crystalline tablet formulation of NMN
Placebo
Other intervention
matching placebo tablets

Treatment groups

90 Participants

are divided into 3 treatment groups

Group A: NMN (MIB-626) for 7 days preoperatively, on day of surgery, and for 3 days postoperativelyExperimental treatment 1 intervention

Group B: NMN administered for 2 days preoperatively, on the day of surgery, and for 3 days postoperativelyExperimental treatment 1 intervention

Group C: PlaceboPlacebo comparator 1 intervention

Trial outcomes

Primary outcomes

NAD+ 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)

Secondary outcomes

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

Other outcomes

Left ventricular ejection fraction (LVEF)

Left ventricular ejection fraction (LVEF) measured by a transesophageal echocardiogram (TEE)

Time frame

change from immediately preoperative to immediate postoperative

Atrial fibrillation

Frequency of new-onset atrial fibrillation. Atrial fibrillation must be confirmed on a 12-lead ECG or a rhythm strip, confirmed by a healthcare provider, or treated (either medically \[e.g., amiodarone\] or with electrical cardioversion)

Time frame

First seven days postoperatively

Vasoactive-inotropic score

The vasoactive-inotropic score is a validated method for integrating all vasoactive medications and their doses on an hourly basis into a single measure. The score ranges from 0 to 100, with higher scores indicating greater cardiovascular support needs.

Time frame

Immediately preoperatively to 24-hours post-incision

Time-to-liberation from vasoactive medications

Time (in hours) from end of cardiopulmonary bypass (CPB) to liberation from all vasopressors and inotropes.

Time frame

End of cardiopulmonary bypass to 24 hours post surgery