Impact of Nicotinamide Riboside (NR) on Kidney Function in Patients Undergoing Cardiac Surgery

Not Applicable

Not yet recruiting

• Conditions: Acute Kidney Injury; Cardiac Valve Disease
• Interventions: Dietary Supplement: Nicotinamide riboside; Other: Placebo

• Registration Number: NCT06521307
• Lead Sponsor: Instituto Nacional de Cardiologia Ignacio Chavez

Brief Summary

Acute kidney injury (AKI) associated with cardiac surgery is the most important complication in adult patients undergoing open heart surgery and is associated with increased mortality and morbidity. In patients in intensive care units, it is the second most common type of AKI after AKI secondary to sepsis. There is currently no specific treatment for AKI. Supportive measures include renal support therapy for patients with severe AKI, and mortality in this subgroup of patients exceeds 50%. Increasing NAD+ with niacinamide has been shown to prevent various etiologies of experimental AKI in mice, and an early pilot study has shown both increased NAD levels following administration of nicotinamide riboside with pterostilbene NPRT and the safety of niacinamide in patients undergoing cardiac surgery.

Detailed Description

AKI associated with cardiac surgery is a condition with a high incidence of morbidity and mortality, without pharmacological interventions approved for its prevention or treatment. As far as we know, there is no study that evaluates the impact of the administration of nicotinamide riboside on renal function in patients undergoing cardiac surgery.

Implementation of this relatively low-cost intervention and adequate safety profile would reduce in-hospital complications in risk patients undergoing cardiac surgery.

Nicotinamide adenine dinucleotide (NAD+) is a cellular factor related to metabolism and longevity. NAD+ is a required cofactor of SIRT1, a nuclear deacetylase that modulates chromatin structure, gene expression, prolongs lifespan in organisms, and ameliorates age-related diseases. Experimental AKI in mice rapidly leads to reduced NAD+ levels in the kidney resulting from a combination of decreased NAD+ biosynthesis and increased NAD+ consumption. Likewise, mice deficient in SIRT1 are more susceptible to AKI and when there is overexpression of SIRT1 they are protected from AKI. These studies describe the modulation of NAD+ and SIRT1 as a potential therapeutic approach in AKI. Similarly, in subjects with AKI, there is evidence of a 50% reduction in plasma NAD. Increasing NAD+ with niacinamide has been shown to prevent various etiologies of experimental AKI in mice, and an early pilot study has shown both increased NAD levels following administration of nicotinamide riboside with pterostilbene NPRT and the safety of niacinamide in patients undergoing cardiac surgery.

Study Timeline

• Status Verified: 2024-07
• Study First Submitted: 2024-07-16
• Study Start: 2024-07-24
• Study First Submitted QC: 2024-07-24
• Last Update Submitted: 2024-07-24
• Study First Posted: 2024-07-25
• Last Update Posted: 2024-07-25
• Primary Completion: 2025-07-31
• Study Completion: 2026-07-24

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

• Heart valve replacement surgery
• Sign of informed consent

Exclusion Criteria

• Allergy to any of the components
• Platelet count less than 100,000
• Weight less than 50Kg or over 100Kg
• Any type of infectious disease (e. g, Endocarditis)
• GFR less or equal to 15ml/min/m2 or with renal replacement therapy
• IV or oral contrast medium 72 hrs prior recruitment
• LRA 7 days prior to surgery

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Riboside (RN) arm	Nicotinamide riboside	NAD Riboside 2000 mg by oral intake at enrollment 24hrs prior surgery, 3000mg prior undergoing surgery with NG tube, 3000mg 12 hrs post-surgery with NG tube and 2000mg 24 hrs after intervention by oral intake.
Placebo arm	Placebo	NAD Riboside 2000 mg by oral intake at enrollment 24hrs prior surgery, 3000mg prior undergoing surgery with NG tube, 3000mg 12 hrs post-surgery with NG tube and 2000mg 24 hrs after intervention by oral intake.

Primary Outcome Measures

Name	Time	Method
Impact of nicotinamide riboside (NR) on kidney function in patients undergoing cardiac surgery.	2 years	The NAD+ and NADH will be measured with the quantitation of the cofactor SIRT1 with a human SIRT1 ELISA kit (novus, NBP2-80300) and a fluorogenic assay SIRT1 CS1040 and flow cytometry.

Trial Locations

Locations (1)

Insituto Nacional de Cardiología Ignacio Chávez; 🇲🇽 Mexico, Mexico