Nicotinamide Riboside in LVAD Recipients

NCT03727646 | Completed Early Phase 1 Results DMC FDA Drug

• 1 other identifier: STUDY00005431
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

While preliminary data show that oral nicotinamide riboside (NR) supplementation increases myocardial levels of oxidized nicotine-adenine dinucleotide (NAD+) levels in mice, there has been no direct evidence that suggests oral NR increases NAD+ levels or improves mitochondrial function in human hearts. This Pilot Study is designed to obtain feasibility data for a planned, larger study testing the hypothesis that oral NR supplementation will increase myocardial NAD+ levels and improve cardiomyocyte mitochondrial function in participants with advanced heart failure planned for elective left ventricular assist device (LVAD) implantation. To demonstrate safety and feasibility of NR in this patient population, the investigators propose to enroll 5 participants planned for LVAD implantation in a Pilot Study of NR in which participants will receive NR, up-titrated over 3 days to a final NR dose of 1000mg twice daily. Blood and myocardial tissue analyses collected previously from age- and gender-matched LVAD recipients will serve as controls.

Conditions

Heart Failure，Congestive; Heart Failure New York Heart Association Class IV; Mitochondrial Alteration

Outcome Measures

Primary Outcomes (2)

• Number of Participates Experiencing Treatment-Emergent Adverse Events (Safety and Tolerability)

  Participants experiencing adverse events during the time they are on the study drug. Regarding time frame: Day 1 is the first day that the study subjects start taking the study drug (NR). The participants stop taking the study drug on the day before his/her LVAD surgery (between Days 6 and 14).

  from Day 1 receiving NR to the day before LVAD surgery (between Day 6-Day 14)

• Pre/Post NR Comparison of Maximal Mitochondrial Respiration in PBMCs

  Comparison of maximal mitochondrial respiration in PBMCs on the Day of LVAD Surgery Pre- vs Post-NR Administration

  from Day 1 receiving NR to the day before LVAD surgery (between Day 6-Day 14)

Secondary Outcomes (3)

• Effect of NR on Whole Blood NAD+ Levels

  from Day 1 receiving NR to the day before LVAD surgery (between Day 6-Day 14)

• Between-group Comparison of Mitochondrial Respiration (Seahorse Assay) in Isolated Peripheral Blood Mononuclear Cells (PBMCs)

  Data collected 6-14 days after study intervention (oral NR) has been initiated.

• Between-group Comparison of Whole Blood NAD+ Levels

  Data collected 6-14 days after study intervention (oral NR) has been initiated.

Study Arms (2)

Open-label nicotinamide riboside

EXPERIMENTAL

Participants scheduled to receive an LVAD will be prescribed nicotinamide riboside (NR) according to the following administration schedule: Dose Escalation Day 1: 250 mg (1 capsule) twice daily (total daily intake = 500 mg) Day 2: 500 mg (2 capsules) twice daily (total daily intake = 1000 mg) Day 3: 1000 mg (4 capsules) twice daily (total daily intake = 2000 mg) Dose Maintenance Day 4: 1000 mg (4 capsules) twice daily Day 5-14 as applicable thru Day Before Surgery: 1000 mg (4 capsules) twice daily Washout Day of LVAD Surgery and/or Day 15: None

Dietary Supplement: Nicotinamide riboside

Baseline controls

NO INTERVENTION

Patients previously receiving LVADs, in whom blood and myocardial tissue assays for NAD+ levels and mitochondrial function were performed.

Interventions

Nicotinamide riboside DIETARY_SUPPLEMENT

nicotinamide riboside supplied as 250mg capsules

Open-label nicotinamide riboside

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of advanced heart failure.
• Planned elective LVAD implantation surgery with patient agreements for candidacy in place as required by UWMC.
• Hospital inpatient at time of enrollment.
• Ability to undergo Study procedures.
• Willingness/ability to provide informed consent.

You may not qualify if:

• Current smoking
• Receiving certain concurrent supplements (to be determined at discretion of the PI). Note that UWMC Nutrition Care standards call for a general multivitamin (1 tab PO daily) as part of the advanced heart failure therapy (AHFT) work-up.
• Known allergies to niacin or nicotinamide.
• Hepatic, renal, endocrine, or neurological disease that disqualify them from consideration for LVAD implantation.
• Inability to perform Study visits or procedures.
• Unwillingness/inability to provide informed consent.

Sponsors & Collaborators

• University of Washington: lead
• American Heart Association: collaborator

Study Sites (1)

University of Washington

Seattle, Washington, 98195, United States

Location

Related Publications (1)

• Zhou B, Wang DD, Qiu Y, Airhart S, Liu Y, Stempien-Otero A, O'Brien KD, Tian R. Boosting NAD level suppresses inflammatory activation of PBMCs in heart failure. J Clin Invest. 2020 Nov 2;130(11):6054-6063. doi: 10.1172/JCI138538.

  PMID: 32790648 RESULT

MeSH Terms

Conditions

Heart Failure

Interventions

nicotinamide-beta-riboside

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Results Point of Contact

• Title: Dr. Kevin Douglas O'Brien
• Organization: University of Washington

cardiac@uw.edu

2065984300

Study Officials

• Kevin O'Brien, MD

  University of Washington

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Study biostatistician will be blinded to group (NR vs. untreated controls)
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, School of Medicine: Department of Medicine: Cardiology: Clinical

Model Details: This single-center, open-label study will compare blood and myocardial NAD+ levels and other mitochondrial endpoints in participants with end-stage heart failure receiving open-label nicotinamide riboside prior to LVAD implantation to similar endpoints from patients previously undergoing LVAD implantation.

Study Record Dates

• First Submitted: October 16, 2018
• First Posted: November 1, 2018
• Study Start: September 26, 2018
• Primary Completion: November 26, 2018
• Study Completion: November 26, 2018
• Last Updated: September 20, 2024
• Results First Posted: September 20, 2024

Record last verified: 2024-05

Locations

US (1)