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Heart Failure，CongestiveEarly Phase 1PilotNR-LVADNCT03727646

Nicotinamide Riboside in LVAD Recipients

A Early Phase 1 study testing Nicotinamide riboside in people with Heart Failure，Congestive and Heart Failure New York Heart Association Class IV, run by University of Washington at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 75 years
What is being tested?
Nicotinamide riboside
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
5 participants
Where
1 siteUnited States
Study dates
26 Sep 2018to 26 Nov 2018
Phase
Early Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
  • Women who are currently pregnant or who wish to become pregnant over the course of the study follow-up are not allowed to join this study. This exclusion is built into the LVAD candidate selection process.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Washington

    Seattle, Washington, 98195

Other trials in United States

About this study

Official title: Pilot Study of Preoperative Nicotinamide Riboside (Vitamin B3) Supplementation in Patients Undergoing Elective Left Ventricular Assist Device (LVAD) Implantation

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.

Read the detailed description

This Pilot Study will examine the following Aims:

Aim 1: Enroll 5 participants scheduled for elective left ventricular assist device (LVAD) placement into an open-label study of nicotinamide riboside (NR).

  1. Participants will have labs (including safety panels) drawn at baseline (Day 1), then receive escalating doses of NR to a maximum dose of 1000mg twice daily by Day 3. Participants will be continued on NR at 1000mg twice daily until LVAD implantation surgery.

On the morning of LVAD implantation Surgery (Day 5 or later), participants will have final labs drawn. Samples of fresh cardiac tissue removed from the left ventricular apex during LVAD implantation surgery will be collected in the operating room. The primary analyses will be performed on NR-treated participants who were on the maximum NR dose of 1000mg twice daily for at least 2 days prior to LVAD implantation surgery. The maximum duration of NR administration will be capped at 14 days. If the surgery doesn't happen by then, the participant will be withdrawn from the study.

Aim 2: Determine the effect of NR (as compared to historical controls) on levels of the oxidized and reduced forms of nicotine-adenine dinucleotide (NAD+ and NADH, respectively), mitochondrial function and its regulation through modifications of the epigenome in the failing myocardium.

  1. Measure NAD+ and NADH levels in the blood and myocardium of the participants.
  2. Assess mitochondrial morphology and function in cardiac tissue using, respectively, electron microscopy (EM) and isolated mitochondria.
  3. Determine protein acetylation in the mitochondrial and non-mitochondrial compartments and changes in nuclear gene regulation.

Aim 3: Test the hypothesis that NR improves mitochondrial function and reduces inflammatory response in heart failure (HF) patients receiving NR (as compared to historical controls).

  1. Measure mitochondrial function in peripheral blood mononucleated cells (PBMC).
  2. Determine the inflammatory response in PBMC.
  3. Compare effects on the circulating inflammasome vs. myocardial inflammation.
Being tested
Nicotinamide riboside
Medical subject headings
Heart Failure

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Nicotinamide ribosideDietary supplement

    nicotinamide riboside supplied as 250mg capsules

Study groups in NCT03727646
Study groupRoleWhat they receive
Open-label nicotinamide ribosideExperimentalParticipants 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
Receives: Dietary Supplement: Nicotinamide riboside
Baseline controlsNo interventionPatients previously receiving LVADs, in whom blood and myocardial tissue assays for NAD+ levels and mitochondrial function were performed.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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).

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

  2. 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

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

Secondary outcomes (3)

  1. Effect of NR on Whole Blood NAD+ Levels

    Change in whole blood NAD+ levels from Baseline to Day of Surgery in NR-treated participants

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

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

    Comparison of mitochondrial respiration (Seahorse assay) in isolated peripheral blood mononuclear cells (PBMCs) on the Day of LVAD Surgery in NR-treated vs. historical control patients

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

  3. Between-group Comparison of Whole Blood NAD+ Levels

    Comparison of whole blood NAD+ levels on the Day of LVAD Surgery in NR-treated vs. historical control patients

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Nov 2018
  2. Study start26 Sep 2018
  3. Primary completion26 Nov 2018
  4. Study completion26 Nov 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Early Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Model description
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.
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
5 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03727646
Sponsor's protocol ID
STUDY00005431
Acronym
PilotNR-LVAD
Status last verified
May 2024
First submitted
16 Oct 2018
Last updated
20 Sep 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 32790648

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing Nicotinamide riboside in people with Heart Failure，Congestive and Heart Failure New York Heart Association Class IV, run by University of Washington at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 20 Sep 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participates Experiencing Treatment-Emergent Adverse Events (Safety and Tolerability) (time frame: from Day 1 receiving NR to the day before LVAD surgery (between Day 6-Day 14)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03727646, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Sep 2024.

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