Nicotinamide Mononucleotide in Patients Undergoing CABG Surgery

Официальное название

Randomized Clinical Trial of β Nicotinamide Mononucleotide in Patients Undergoing CABG Surgery

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат MIB-626
  An orally-administered stable crystalline tablet formulation of NMN
• Другое Placebo
  matching placebo tablets

Первичные конечные точки

• NAD+ concentration in the myocardial tissue [Срок оценки: Intraoperatively (single time point)]

Вторичные конечные точки (12)

• Intracellular levels of NAD+ and related metabolites [Срок оценки: Intraoperatively (single time point)]
• Circulating levels of NAD+ and related metabolites [Срок оценки: Baseline to day 90]
• Markers of cardiac injury/dysfunction [Срок оценки: Preoperatively, on ICU arrival, and on postoperative days 1-4]
• Acute kidney injury (AKI) [Срок оценки: 7 days post-operatively]
• Serum creatinine (SCr) [Срок оценки: Immediately pre-operative to 7 days post-operative]
• Cystatin C [Срок оценки: Preoperatively, on ICU arrival, and on postoperative days 1-4]
• Neutrophil gelatinase-associated lipocalin (NGAL) [Срок оценки: Preoperatively, on ICU arrival, and on postoperative days 1-4]
• Kidney Injury Molecule-1 (KIM-1) [Срок оценки: Preoperatively, on ICU arrival, and on postoperative days 1-4]
• NMN level [Срок оценки: Preoperatively, on ICU arrival, and on postoperative days 1-4]
• 2PY Level [Срок оценки: Preoperatively, on ICU arrival, and on postoperative days 1-4]
• N-Methylnicotinamide level [Срок оценки: Preoperatively, on ICU arrival, and on postoperative days 1-4]
• nicotinamide level [Срок оценки: Preoperatively, on ICU arrival, and on postoperative days 1-4]

Критерии участия

Критерии включения

• Age ≥18 years
• Scheduled to undergo elective isolated CABG surgery with cardiopulmonary bypass (CPB)
• At increased risk of postoperative complications based on ≥1 of the following:

• Age ≥65 years
• eGFR <45 ml/min/1.73m2
• Documented history of congestive heart failure or left ventricular ejection fraction (LVEF) ≤40% within 6 months before surgery
• Diabetes mellitus and urine albumin-to-creatinine ratio >30 mg/g creatinine
• Peripheral arterial disease
• Anemia, defined as hemoglobin <10 g/dl
• Prior cardiac surgery

Критерии исключения

• Any of the following laboratory abnormalities at the time of screening:

• ALT >3-fold the upper limit of normal
• eGFR <30 ml/min/1.73m2 or ESKD on dialysis
• Hemoglobin <8 g/dl
• History of gastric bypass or malabsorption
• Active alcohol or illicit substance use in the prior 6 months
• Participation in an investigational trial to evaluate pharmaceuticals or biologics within the past 3 months or 5 half-lives, whichever is shorter
• Pregnant or breast-feeding
• 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
• Current use of niacin >100 mg/day or NMN, nicotinamide, or nicotinamide riboside at any dose
• Conflict with other research studies
• Any condition which, in the judgement of the investigator, might increase the risk to the participant

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

США · 1 центр

• Brigham and Women's Hospital — Boston

Идентификаторы

NCT: NCT07013591 · 2025P000420 · 1U01AG089040-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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