Heart Failure, SystolicEarly Phase 1NRIINCT04528004
Mechanistic Studies of Nicotinamide Riboside in Human Heart Failure
A Early Phase 1 study testing Nicotinamide riboside in people with Heart Failure, Systolic and Heart Failure NYHA Class IV, run by University of Washington at 1 site in United States.
Trial summary
Preliminary animal studies by ourselves and others suggest that the dietary supplement, nicotinamide riboside (NR), may improve cardiac function in heart failure (HF) by increasing cellular levels of its metabolite, nicotinamide adenine dinucleotide (NAD+, NADH). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Failure, Systolic, Heart Failure NYHA Class IV, Metabolic Disturbance
- What is being tested?
- Nicotinamide riboside
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 32 participants
- Where
- 1 siteUnited States
- Study dates
- 26 Sep 2020to 31 Jul 2025
- Phase
- Early Phase 1
- Are there results?
- Not yet: the study is under way
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- End-stage heart failure due to ischemic or non-ischemic cardiomyopathy
- If implanted for destination therapy indication, must have New Your Heart Association (NYHA) Class IV Heart Failure AND left ventricular ejection fraction (LVEF) <25% OR maximum minute consumption of oxygen (VO2) <14 OR on requirement for continuous intravenous inotropes
- Meet clinical and socioeconomic screening criteria for elective LVAD implantation by the University of Washington Mechanical Circulatory Support Program
- Scheduled (or soon to be scheduled) for elective LVAD implantation
- Age >18 years
Who cannot join
- End-stage heart failure due to causes other than ischemic or non-ischemic cardiomyopathy (e.g., valvular, hypertrophic or infiltrative cardiomyopathies).
- Disease that disqualifies from consideration for LVAD implantation by the University of Washington program:
- Cirrhosis as evidenced by liver biopsy
- Irreversible, severe renal disease (estimated glomerular filtration rate (eGFR) <30) or on chronic dialysis
- Untreated thyroid disease (hyper- or hypo-thyroidism)
- Severe complications of diabetes, such as diabetes-related amputation, severe retinopathy, peripheral neuropathy or diabetic renal disease (eGFR <30)
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- Tissue physiology or other factors that, in the opinion of the Cardiac Surgeons, make the patient at unacceptably high risk for adverse outcomes.
- Non-compliance with current treatments, including failure to follow prescribed therapies, such as medications, clinic visits, diagnostic testing and behavioral contracts
- Active use/abuse of illicit substances
- Lack of adequate caregiver support to help patient manage LVAD
- Known allergies to niacin, nicotinamide or warfarin
- Inability to perform Study visits or procedures
- Unwillingness/inability to provide informed consent.
- Participants considered by the attending cardiologist and/or the investigator to be unsuitable for the study
Trial locations and contacts
1 site in 1 country.
About this study
Preliminary animal studies by ourselves and others suggest that the dietary supplement, nicotinamide riboside (NR), may improve cardiac function in heart failure (HF) by increasing cellular levels of its metabolite, nicotinamide adenine dinucleotide (NAD+, NADH). This Study will address a key gap in current knowledge by assessing the mechanisms through which raising blood and myocardial NAD+ levels in humans mediates changes in mitochondrial function, protein and epigenetic modifications, as well as inflammation. Human myocardium will be obtained after 4-14 days of oral NR supplementation from advanced heart failure patients undergoing elective left ventricular assist device (LVAD) implantation. Positive results would provide evidence to proceed with further studies of NR as a mitochondria-targeted metabolic therapy in heart failure.
Read the detailed description
To definitively demonstrate the effects of increasing NAD+ levels in HF patients, this randomized, placebo-controlled trial of NR in 40 participants scheduled for elective LVAD surgery with the underlying hypotheses that those randomized to NR will have higher myocardial NAD+ levels, improved mitochondrial function, restored gene expression and reduced inflammatory response as compared to participants randomized to placebo. To this end, the study has the following specific aims:
Aim 1: Randomize 40 participants undergoing elective LVAD placement into a double-blind, placebo-controlled study of NR vs. placebo at an NR:placebo ratio of 2:1.
- Participants will have labs (including safety panels) drawn at baseline (Day 1), with NR or placebo dose escalation to 1000mg twice daily by Day 3, and the last dose administered the evening prior to surgery.
- Final labs will be drawn on the day of surgery, and samples of fresh cardiac tissue removed from the left ventricular apex during LVAD implantation surgery will be collected in the operating room.
Aim 2: Determine the effect of NR vs. placebo on NAD(H) levels, mitochondrial function and its regulation through epigenetic modifications in the failing myocardium.
- Measure NAD+ and NADH levels in the blood and myocardium of the participants.
- Assess mitochondrial morphology and function in cardiac tissue using electron microscopy (EM) and isolated mitochondria.
- Determine changes in protein acetylation in the mitochondrial and non-mitochondrial compartments and in nuclear gene regulation.
Aim 3: Test the hypothesis that NR improves mitochondrial function and reduces inflammatory response in HF patients.
- Measure mitochondrial function in peripheral blood mononucleated cells (PBMC).
- Determine the inflammatory response in PBMC from NR-treated vs. placebo participants.
- Compare effects on the circulating inflammasome vs. myocardial inflammation.
- Being tested
- Nicotinamide riboside, Placebo
- Medical subject headings
- Heart Failure, Systolic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nicotinamide ribosideDrug
Nicotinamide riboside 250mg capsules
PlaceboOther
Matching placebo 250mg capsules
| Study group | Role | What they receive |
|---|---|---|
| Nicotinamide riboside | Experimental | Participants randomized to Nicotinamide Riboside (NR) and scheduled to receive an LVAD will receive nicotinamide riboside (NR) capsules 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: Drug: Nicotinamide riboside |
| Placebo | Placebo comparator | Participants randomized to Placebo and scheduled to receive an LVAD will receive Placebo capsules 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: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Between-group comparisons of whole blood NAD+ levels
Comparisons of whole blood NAD+ levels on the Day of LVAD Surgery in participants randomized to NR vs. placebo
Measured: Up to 14 days
Secondary outcomes (7)
Between-group comparisons of myocardial NAD(H) levels
Comparisons of myocardial NAD(H) levels in participants randomized to NR vs. placebo
Measured: Up to 14 days
Between-group comparisons of myocardial mitochondrial respiratory function.
Comparisons of myocardial mitochondrial respiration in participants randomized to NR vs. placebo
Measured: Up to 14 days
Between-group comparisons of myocardial mitochondrial morphology.
Comparisons of myocardial mitochondrial morphology, by electron microscopy, in participants randomized to NR vs. placebo
Measured: Up to 14 days
Between-group comparisons of myocardial protein acetylation
Comparisons of myocardial protein acetylation in participants randomized to NR vs. placebo
Measured: Up to 14 days
Between-group comparisons of myocardial gene expression by RNA-seq and the myocardial epigenome by ATAC-seq
Comparisons, NR vs. placebo-treated participants, of myocardial gene expression by RNA sequencing (RNA-seq) and the myocardial epigenome by the Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq)
Measured: Up to 14 days
Between-group comparisons of inflammatory markers in blood
Comparisons, in patients randomized to NR vs. placebo of: 1) plasma levels of highly-sensitive C-reactive protein, interleukin-1beta, interleukin-6, interleukin-18, tumor necrosis factor-alpha, and NLR family pyrin domain containing 3 (NLRP3), as well as 2) mRNA expression of these cytokines in isolated peripheral blood mononuclear cells
Measured: Up to 14 days
Between-group comparisons of inflammatory markers in myocardium
Comparisons by quantitative morphometry of immunohistochemical staining of macrophages (including M1 and M2 phenotypes) in myocardium in participants randomized to NR vs. placebo
Measured: Up to 14 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Aug 2020
- Study start26 Sep 2020
- Primary completion30 Nov 2024
- Study completion31 Jul 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heart Failure, SystolicStudies of the same condition, open and under way.
- More trials run by University of WashingtonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized, interventional trial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Washington
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Kevin O'Brien, University of Washington
- Investigators
- Kevin D O'Brien, MD, Principal investigator, University of Washington
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04528004
- Sponsor's protocol ID
- STUDY00007432
- Other IDs
- 1R01HL144937-01A1
- Acronym
- NRII
- Status last verified
- Mar 2025
- First submitted
- 18 Aug 2020
- Last updated
- 25 Mar 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: The Investigators plan to deposit study results in BioLINCC. The Study will generate data that is primarily applicable to the basic research questions that are proposed. It is the explicit intention of the Investigators that these data will be placed in a readily accessible public database. The Investigators anticipate placing de-identified study results into the NHLBI data repository at the Biologic Specimen and Data Repository Information Coordinating Center (BioLINCC) (biolincc.nhlbi.nih.gov/home/). Data sets will be submitted no later than three years after the final study dataset is locked or two years after the core manuscript from the trial has been published, whichever comes first.
Study at a glance
From the registry record, last updated by the sponsor on 25 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mechanistic Studies of Nicotinamide Riboside in Human Heart Failure
- ClinicalTrials.gov ID
- NCT04528004
- Acronym / sponsor ID
- NRII / STUDY00007432
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 32 participants (actual)
- Lead sponsor
- University of WashingtonUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- 26 Sep 2020 (actual)
- Primary completion
- 30 Nov 2024 (actual)
- Study completion
- 31 Jul 2025 (estimated)
- First posted
- 27 Aug 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Preliminary animal studies by ourselves and others suggest that the dietary supplement, nicotinamide riboside (NR), may improve cardiac function in heart failure (HF) by increasing cellular levels of its metabolite, nicotinamide adenine dinucleotide (NAD+, NADH). This Study will address a key gap in current knowledge by assessing the mechanisms through which raising blood and myocardial NAD+ levels in humans mediates changes in mitochondrial function, protein and epigenetic modifications, as well as inflammation. Human myocardium will be obtained after 4-14 days of oral NR supplementation from advanced heart failure patients undergoing elective left ventricular assist device (LVAD) implantation. Positive results would provide evidence to proceed with further studies of NR as a mitochondria-targeted metabolic therapy in heart failure.
Detailed description
To definitively demonstrate the effects of increasing NAD+ levels in HF patients, this randomized, placebo-controlled trial of NR in 40 participants scheduled for elective LVAD surgery with the underlying hypotheses that those randomized to NR will have higher myocardial NAD+ levels, improved mitochondrial function, restored gene expression and reduced inflammatory response as compared to participants randomized to placebo. To this end, the study has the following specific aims:
Aim 1: Randomize 40 participants undergoing elective LVAD placement into a double-blind, placebo-controlled study of NR vs. placebo at an NR:placebo ratio of 2:1.
- Participants will have labs (including safety panels) drawn at baseline (Day 1), with NR or placebo dose escalation to 1000mg twice daily by Day 3, and the last dose administered the evening prior to surgery.
- Final labs will be drawn on the day of surgery, and samples of fresh cardiac tissue removed from the left ventricular apex during LVAD implantation surgery will be collected in the operating room.
Aim 2: Determine the effect of NR vs. placebo on NAD(H) levels, mitochondrial function and its regulation through epigenetic modifications in the failing myocardium.
- Measure NAD+ and NADH levels in the blood and myocardium of the participants.
- Assess mitochondrial morphology and function in cardiac tissue using electron microscopy (EM) and isolated mitochondria.
- Determine changes in protein acetylation in the mitochondrial and non-mitochondrial compartments and in nuclear gene regulation.
Aim 3: Test the hypothesis that NR improves mitochondrial function and reduces inflammatory response in HF patients.
- Measure mitochondrial function in peripheral blood mononucleated cells (PBMC).
- Determine the inflammatory response in PBMC from NR-treated vs. placebo participants.
- Compare effects on the circulating inflammasome vs. myocardial inflammation.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Randomized, interventional trial
| Arm | Type | Receives |
|---|---|---|
| Nicotinamide riboside | Experimental | Drug: Nicotinamide ribosideParticipants randomized to Nicotinamide Riboside (NR) and scheduled to receive an LVAD will receive nicotinamide riboside (NR) capsules 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 |
| Placebo | Placebo comparator | Other: PlaceboParticipants randomized to Placebo and scheduled to receive an LVAD will receive Placebo capsules 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- End-stage heart failure due to ischemic or non-ischemic cardiomyopathy
- Meet clinical and socioeconomic screening criteria for elective LVAD implantation by the University of Washington Mechanical Circulatory Support Program
- Scheduled (or soon to be scheduled) for elective LVAD implantation
- Age >18 years
Key exclusion criteria (14 listed)
- End-stage heart failure due to causes other than ischemic or non-ischemic cardiomyopathy (e.g., valvular, hypertrophic or infiltrative cardiomyopathies).
- Disease that disqualifies from consideration for LVAD implantation by the University of Washington program:
- Tissue physiology or other factors that, in the opinion of the Cardiac Surgeons, make the patient at unacceptably high risk for adverse outcomes.
- Non-compliance with current treatments, including failure to follow prescribed therapies, such as medications, clinic visits, diagnostic testing and behavioral contracts
- Active use/abuse of illicit substances
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Nicotinamide ribosideNicotinamide riboside 250mg capsules | Drug | Nicotinamide riboside |
| PlaceboMatching placebo 250mg capsules | Other | Placebo |
Primary outcome
Between-group comparisons of whole blood NAD+ levels
Time frame: Up to 14 days
Comparisons of whole blood NAD+ levels on the Day of LVAD Surgery in participants randomized to NR vs. placebo
7 secondary outcomes
Between-group comparisons of myocardial NAD(H) levels
Time frame: Up to 14 days
Between-group comparisons of myocardial mitochondrial respiratory function.
Time frame: Up to 14 days
Between-group comparisons of myocardial mitochondrial morphology.
Time frame: Up to 14 days
Between-group comparisons of myocardial protein acetylation
Time frame: Up to 14 days
Between-group comparisons of myocardial gene expression by RNA-seq and the myocardial epigenome by ATAC-seq
Time frame: Up to 14 days
Between-group comparisons of inflammatory markers in blood
Time frame: Up to 14 days
Between-group comparisons of inflammatory markers in myocardium
Time frame: Up to 14 days
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Mar 2025.
- Individual participant dataSharing planned: Yes. The Investigators plan to deposit study results in BioLINCC. The Study will generate data that is primarily applicable to the basic research questions that are proposed. It is the explicit intention of the Investigators that these data will be placed in a readily accessible public database. The Investigators anticipate placing de-identified study results into the NHLBI data repository at the Biologic Specimen and Data Repository Information Coordinating Center (BioLINCC) (biolincc.nhlbi.nih.gov/home/). Data sets will be submitted no later than three years after the final study dataset is locked or two years after the core manuscript from the trial has been published, whichever comes first.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kevin D O'Brien, MD principal investigator
University of Washington
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Nicotinamide riboside in people with Heart Failure, Systolic and Heart Failure NYHA 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 14 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: under way, not looking for participants, as of the sponsor's last update on 25 Mar 2025. 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. Some participants in this study may receive a placebo. 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?
This study is still under way. Results are not available in the source record yet.
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?
Between-group comparisons of whole blood NAD+ levels (time frame: Up to 14 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 25 Mar 2025.