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

NCT06521307 | Not Yet Recruiting

• 1 other identifier: SIRT1-NR.AKI
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

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.

Conditions

Acute Kidney Injury; Cardiac Valve Disease

Keywords

Nicotinamide Riboside; NAD+; NADH; SIRT1; AKI; Cardiac surgery; TIMP-2; IGFBP7; NGAL

Outcome Measures

Primary Outcomes (1)

• Impact of nicotinamide riboside (NR) on kidney function in patients undergoing cardiac surgery.

  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.

  2 years

Study Arms (2)

Riboside (RN) arm

EXPERIMENTAL

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.

Dietary Supplement: Nicotinamide riboside

Placebo arm

PLACEBO COMPARATOR

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.

Other: Placebo

Interventions

Nicotinamide riboside DIETARY_SUPPLEMENT

We will recruit the participant 24 hrs prior intervention, once the participant decides to enroll, we will administer by oral intake the supplement or placebo due to the result at randomizer.org. The first NAD Riboside arm will be administered by oral intake with 2000 mg at enrollment, then we will administer 3000mg prior undergoing surgery with NG tube, 3000mg 12 hrs post-surgery with NG tube and 2000mg by oral intake 24 hrs after intervention. All the administrations with NG tube will be flushed with 0.9% saline solution.

Also known as: NADH Riboside

Riboside (RN) arm

Placebo OTHER

We will recruit the participant 24 hrs prior intervention, once the participant decides to enroll, we will administer by oral intake the supplement or placebo due to the result at randomizer.org. The first dose of placebo arm will be administered by oral intake with 2000 mg at enrollment, then we will administer 3000mg prior undergoing surgery with NG tube, 3000mg 12 hrs post-surgery with NG tube and 2000mg by oral intake 24 hrs after intervention. All the administrations with NG tube will be flushed with 0.9% saline solution.

Placebo arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Heart valve replacement surgery
• Sign of informed consent

You may not qualify if:

• 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

Sponsors & Collaborators

• Instituto Nacional de Cardiologia Ignacio Chavez: lead

Study Sites (1)

Insituto Nacional de Cardiología Ignacio Chávez

México, 14080, Mexico

Location

Related Publications (12)

• Wang Y, Bellomo R. Cardiac surgery-associated acute kidney injury: risk factors, pathophysiology and treatment. Nat Rev Nephrol. 2017 Nov;13(11):697-711. doi: 10.1038/nrneph.2017.119. Epub 2017 Sep 4.

  PMID: 28869251 RESULT

• Allegretti AS, Steele DJ, David-Kasdan JA, Bajwa E, Niles JL, Bhan I. Continuous renal replacement therapy outcomes in acute kidney injury and end-stage renal disease: a cohort study. Crit Care. 2013 Jun 20;17(3):R109. doi: 10.1186/cc12780.

  PMID: 23782899 RESULT

• Zhang H, Ryu D, Wu Y, Gariani K, Wang X, Luan P, D'Amico D, Ropelle ER, Lutolf MP, Aebersold R, Schoonjans K, Menzies KJ, Auwerx J. NAD(+) repletion improves mitochondrial and stem cell function and enhances life span in mice. Science. 2016 Jun 17;352(6292):1436-43. doi: 10.1126/science.aaf2693. Epub 2016 Apr 28.

  PMID: 27127236 RESULT

• Imai S, Armstrong CM, Kaeberlein M, Guarente L. Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase. Nature. 2000 Feb 17;403(6771):795-800. doi: 10.1038/35001622.

  PMID: 10693811 RESULT

• Guarente L. Franklin H. Epstein Lecture: Sirtuins, aging, and medicine. N Engl J Med. 2011 Jun 9;364(23):2235-44. doi: 10.1056/NEJMra1100831. No abstract available.

  PMID: 21651395 RESULT

• Ralto KM, Rhee EP, Parikh SM. NAD+ homeostasis in renal health and disease. Nat Rev Nephrol. 2020 Feb;16(2):99-111. doi: 10.1038/s41581-019-0216-6. Epub 2019 Oct 31.

  PMID: 31673160 RESULT

• Poyan Mehr A, Tran MT, Ralto KM, Leaf DE, Washco V, Messmer J, Lerner A, Kher A, Kim SH, Khoury CC, Herzig SJ, Trovato ME, Simon-Tillaux N, Lynch MR, Thadhani RI, Clish CB, Khabbaz KR, Rhee EP, Waikar SS, Berg AH, Parikh SM. De novo NAD+ biosynthetic impairment in acute kidney injury in humans. Nat Med. 2018 Sep;24(9):1351-1359. doi: 10.1038/s41591-018-0138-z. Epub 2018 Aug 20.

  PMID: 30127395 RESULT

• Simic P, Vela Parada XF, Parikh SM, Dellinger R, Guarente LP, Rhee EP. Nicotinamide riboside with pterostilbene (NRPT) increases NAD+ in patients with acute kidney injury (AKI): a randomized, double-blind, placebo-controlled, stepwise safety study of escalating doses of NRPT in patients with AKI. BMC Nephrol. 2020 Aug 13;21(1):342. doi: 10.1186/s12882-020-02006-1.

  PMID: 32791973 RESULT

• Martens CR, Denman BA, Mazzo MR, Armstrong ML, Reisdorph N, McQueen MB, Chonchol M, Seals DR. Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults. Nat Commun. 2018 Mar 29;9(1):1286. doi: 10.1038/s41467-018-03421-7.

  PMID: 29599478 RESULT

• Castro-Marrero J, Cordero MD, Segundo MJ, Saez-Francas N, Calvo N, Roman-Malo L, Aliste L, Fernandez de Sevilla T, Alegre J. Does oral coenzyme Q10 plus NADH supplementation improve fatigue and biochemical parameters in chronic fatigue syndrome? Antioxid Redox Signal. 2015 Mar 10;22(8):679-85. doi: 10.1089/ars.2014.6181. Epub 2014 Dec 18.

  PMID: 25386668 RESULT

• Schwarzmann L, Pliquett RU, Simm A, Bartling B. Sex-related differences in human plasma NAD+/NADH levels depend on age. Biosci Rep. 2021 Jan 29;41(1):BSR20200340. doi: 10.1042/BSR20200340.

  PMID: 33393613 RESULT

• Marin-Hernandez A, Gallardo-Perez JC, Rodriguez-Enriquez S, Encalada R, Moreno-Sanchez R, Saavedra E. Modeling cancer glycolysis. Biochim Biophys Acta. 2011 Jun;1807(6):755-67. doi: 10.1016/j.bbabio.2010.11.006. Epub 2010 Nov 24.

  PMID: 21110941 RESULT

MeSH Terms

Conditions

Acute Kidney Injury; Heart Valve Diseases

Interventions

nicotinamide-beta-riboside

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Heart Diseases; Cardiovascular Diseases

Study Officials

• Magdalena Madero

  Instituto Nacional de Cardiología. Ignacio Chávez

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Magdalena Madero, MD

CONTACT

015555732911; madero.magdalena@gmail.com

Ana K. Fernandez, MD

CONTACT

5611133180; anakaren.fyepez@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: The protocol contemplates triple blinding for the intervention. The inclusion and follow-up of patients will be carried out by the team of clinical investigators, who will remain blinded to the assigned group. Assignment to intervention groups will be carried out by an investigator independent of the team of clinical investigators and the clinical management team, who will remain blind to the information and follow-up of the patients. The medical team in charge of hospital treatment (surgery, cardiology, intensive care and nephrology), and the patient himself will remain blind to the assigned intervention group.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD. Head of Nephrology

Model Details: The evaluation of normality will be carried out by the Shapiro-Wilks and Kolmogorov-Smirnov tests. The change or delta in the creatinine value from preoperative to 48 hours postoperative will be calculated, said delta will be analyzed with a t-test between the intervention groups. Other variables will also be compared between groups with t-test or U-Mann-Whitney for quantitative variables. Qualitative variables will be analyzed with a Chi-square test between groups. In secondary objectives, biochemical measurements will be correlated with creatinine values with the Pearson or Spearman test as appropriate to the distribution. Statistical package= SPSS version 23. Statistical significance= alpha 0.05

Study Record Dates

• First Submitted: July 16, 2024
• First Posted: July 25, 2024
• Study Start: July 24, 2024
• Primary Completion: July 31, 2025
• Study Completion (Estimated): July 24, 2026
• Last Updated: July 25, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

ME (1)