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

NCT ID: NCT06521307

Last Updated: 2024-07-25

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

NA

Total Enrollment

100 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-07-24

Study Completion Date

2026-07-24

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Acute Kidney Injury Cardiac Valve Disease

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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
Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators
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.

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Riboside (RN) arm

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.

Group Type EXPERIMENTAL

Nicotinamide riboside

Intervention Type 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.

Placebo arm

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.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type 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.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Nicotinamide riboside

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.

Intervention Type DIETARY_SUPPLEMENT

Placebo

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.

Intervention Type OTHER

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

NADH Riboside

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Instituto Nacional de Cardiologia Ignacio Chavez

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Magdalena Madero

MD. Head of Nephrology

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Magdalena Madero

Role: PRINCIPAL_INVESTIGATOR

Instituto Nacional de Cardiología. Ignacio Chávez

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Insituto Nacional de Cardiología Ignacio Chávez

México, , Mexico

Site Status

Countries

Review the countries where the study has at least one active or historical site.

Mexico

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Magdalena Madero, MD

Role: CONTACT

015555732911 ext. 1273

Ana K. Fernandez, MD

Role: CONTACT

5611133180 ext. 1273

Facility Contacts

Find local site contact details for specific facilities participating in the trial.

Magdalena Madero, MD

Role: primary

015555732911 ext. 1273

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type RESULT
PMID: 28869251 (View on PubMed)

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.

Reference Type RESULT
PMID: 23782899 (View on PubMed)

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.

Reference Type RESULT
PMID: 27127236 (View on PubMed)

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.

Reference Type RESULT
PMID: 10693811 (View on PubMed)

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.

Reference Type RESULT
PMID: 21651395 (View on PubMed)

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.

Reference Type RESULT
PMID: 31673160 (View on PubMed)

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.

Reference Type RESULT
PMID: 30127395 (View on PubMed)

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.

Reference Type RESULT
PMID: 32791973 (View on PubMed)

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.

Reference Type RESULT
PMID: 29599478 (View on PubMed)

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.

Reference Type RESULT
PMID: 25386668 (View on PubMed)

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.

Reference Type RESULT
PMID: 33393613 (View on PubMed)

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.

Reference Type RESULT
PMID: 21110941 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

SIRT1-NR.AKI

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

Heme Arginate in Cardiac Surgery Patients
NCT02142699 COMPLETED PHASE2