Heart Failure, SystolicPhase 1/2NCT03423342
Nicotinamide Riboside in Systolic Heart Failure
A Phase 1/2 study testing nicotinamide riboside in people with Heart Failure, Systolic, run by University of Washington at 1 site in United States.
Trial summary
Mitochondrial dysfunction has been implicated in heart failure (HF), and is associated with an imbalance in intracellular ratio of reduced nicotinamide-adenine dinucleotide (NADH) to oxidized nicotinamide-adenine dinucleotide (NAD), or the NADH/NAD ratio. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Failure, Systolic
- 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
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 19 May 2016to 30 Jun 2019
- Phase
- Phase 1/2
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Men and women aged 18 and older with systolic heart failure [left ventricular ejection fraction (LVEF) by standard 2D echocardiography or radionuclide ventriculography of ≤40%] deemed, in the clinical opinion of their treating cardiologist to be non-ischemic or ischemic in origin.
- Clinically stable (no cardiac procedures or hospitalizations for hospitalizations for cardiac causes, including HF, ischemia or arrhythmia) within the previous 3 months
- Ability to undergo study procedures, including scheduled visits, blood draws and six-minute walk test (6MWT)
- Willingness/ability to provide informed consent
Who cannot join
- Heart failure with preserved ejection fraction (LVEF greater than 40%)
- Heart failure due, in the opinion of their treating cardiologist, to etiologies other than non-ischemic or ischemic. Examples of exclusionary heart failure etiologies include primary valvular disease, or infiltrative or inflammatory cardiomyopathies.
- Cardiac surgery, percutaneous coronary intervention (PCI) or cardiac device implantation within the previous 3 months
- Hospitalizations for cardiovascular causes, including heart failure, chest pain, stroke, transient ischemic attack or arrhythmias within the previous 3 months
- Inability to perform Study visits or procedures (e.g., physical inability to perform 6MWT)
- Unwillingness/inability to provide informed consent
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- ALT greater than 3 times the upper limit of normal, hepatic insufficiency or active liver disease
- Recent history of acute gout
- Chronic renal insufficiency with creatinine ≥2.5mg/dL
- Pregnant (or likely to become pregnant) women
- Significant co-morbidity likely to cause death in the 6 month follow-up period
- Significant active history of substance abuse within the previous 5 years
- Current participation in another long-term clinical trial
- History of intolerance to NR precursor compounds, including niacin or nicotinamide
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Safety and Tolerability of the Nutritional Supplement, Nicotinamide Riboside, in Systolic Heart Failure
Mitochondrial dysfunction has been implicated in heart failure (HF), and is associated with an imbalance in intracellular ratio of reduced nicotinamide-adenine dinucleotide (NADH) to oxidized nicotinamide-adenine dinucleotide (NAD), or the NADH/NAD ratio. In mouse models of HF, we have found that normalization of the NADH/NAD, through supplementation with NAD+ precursors, is associated with improvement in cardiac function. This Study will randomize participants with systolic HF (ejection fraction ≤40%) to treatment with the NAD precursor, nicotinamide riboside (NR) or matching placebo, uptitrated to a final oral dose of 1000mg twice daily, to determine the safety and tolerability of NR in participants with systolic HF.
Read the detailed description
Aim 1: Determine the safety and tolerability of NR in patients with clinically stable, systolic heart failure (LVEF <40%). To accomplish this Aim:
- a total of 30 participants with clinically stable, systolic heart failure (LVEF <40%) will undergo 2:1 randomization to NR 250mg PO twice daily or matching placebo B) NR (or matching placebo), will be increased weekly by 250mg/dose (500mg/day) to a final dose of 1000mg PO twice daily. Clinic visits with labs bi-weekly during dose escalation will assess HF symptoms and monitor labs [B-type natriuretic peptide (BNP), complete blood count (CBC), glycosylated hemoglobin, alanine aminotransferase (ALT), creatine kinase (CK), insulin/glucose, uric acid, electrolytes, blood urea nitrogen (BUN) and creatinine (Cr).
- to ensure intermediate-term safety and tolerability, participants will continue on their maximum tolerated dose (of NR or placebo) through Study Week 12
Aim 2: Determine whether, at the doses employed, NR and NAD are detectable in whole blood.
Aim 3 (Exploratory): Assess the range of potential effect sizes of NR on HF surrogate endpoints using:
- Six-minute walk tests (6MWTs) at each visit (including Screening) to assess functional capacity B) Echocardiography at Baseline and Week 12 to assess LV systolic function (by real-time, 3D echocardiography) and diastolic function (by integrated Doppler and tissue Doppler imaging)
- Conditions
- Heart Failure, Systolic
- Being tested
- nicotinamide riboside, Placebo
- Keywords
- nicotinamide riboside, Nicotinamide-Adenine Dinucleotide
- 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 ribosideDietary supplement
Also called Niagen
nicotinamide riboside capsule
PlaceboDrug
matching placebo capsule
| Study group | Role | What they receive |
|---|---|---|
| Nicotinamide Riboside | Experimental | Nicotinamide riboside will be supplied as 250mg capsules, to be administered orally. The initial dose will be 1 capsule twice daily, followed by weekly up-titration by 1 capsule/dose to a final dose of 4 capsules (1000mg) twice daily at the end of Week 4. Participants will be continued on the final dose up to the final follow up visit (week 12). If, at any step, a dose increase is not tolerated, the maximum previously-tolerated dose will be continued through to week 12. Receives: Dietary Supplement: nicotinamide riboside |
| Placebo | Placebo comparator | Matching placebo will be supplied as 250mg capsules, to be administered orally. The initial dose will be 1 capsule twice daily, followed by weekly up-titration by 1 capsule/dose to a final dose of 4 capsules (1000mg) twice daily at the end of Week 4. Participants will be continued on the final dose up to the final follow up visit (week 12). If, at any step, a dose increase is not tolerated, the maximum previously-tolerated dose will be continued through to week 12. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)
Adverse Events
Measured: up to 12 weeks
Secondary outcomes (3)
On-Trial Change in Whole Blood NAD+ Levels
Between-group comparison of On-Trial Change in Whole Blood NAD+ Levels
Measured: Week 12-Week 0
Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment
Incidence of On-Trial Abnormal Laboratory Values and/or Adverse Events that Are Related to Treatment
Measured: 16 weeks
Effect of NR on Change in Mitochondrial Function (Maximal Oxygen Consumption Rate)
Mitochondrial Respiration in Isolated Peripheral Blood Mononuclear Cells by the Seahorse (R) Assay
Measured: Week 12 - Week 0
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Feb 2018
- Study start19 May 2016
- Primary completion11 Apr 2019
- Study completion30 Jun 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- 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
- Phase 1/2
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Single group
- Model description
- 2:1 randomization to nicotinamide riboside vs. matching placebo
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 30 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
- NCT03423342
- Sponsor's protocol ID
- STUDY00001830
- Other IDs
- 1R21HL126209-01
- Status last verified
- Oct 2022
- First submitted
- 11 Apr 2017
- Last updated
- 16 Nov 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: A de-identified, public access database will be made available two years after publication of the primary study results. Data files will be delivered in electronic format, providing meta-data that completely describes the tables, variables and coding. Both the raw data and the primary analysis files will be included. Primary analysis files are a compilation of key variables used to generate the statistical results, to help assure that investigators reach consistent conclusions when analyzing the data to published results. Data, documentation and all other materials will be delivered to NHLBI, as well as a document that fully describes the data, steps taken to de-identify the data, and quality control procedures. A document summarizing data tables and other files that are being delivered and describing the data manipulations applied to the data to assure data anonymity, including an annotated clinical study report providing the database variable names.
Publications
Wang DD, Airhart SE, Zhou B, Shireman LM, Jiang S, Melendez Rodriguez C, Kirkpatrick JN, Shen DD, Tian R, O'Brien KD. Safety and Tolerability of Nicotinamide Riboside in Heart Failure With Reduced Ejection Fraction. JACC Basic Transl Sci. 2022 Sep 14;7(12):1183-1196. doi: 10.1016/j.jacbts.2022.06.012. eCollection 2022 Dec.
PubMed 36644285
Study at a glance
From the registry record, last updated by the sponsor on 16 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Tolerability of the Nutritional Supplement, Nicotinamide Riboside, in Systolic Heart Failure
- ClinicalTrials.gov ID
- NCT03423342
- Acronym / sponsor ID
- STUDY00001830
- Conditions
- Heart Failure, Systolic
- Keywords
- nicotinamide riboside, Nicotinamide-Adenine Dinucleotide
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- University of WashingtonUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- 19 May 2016 (actual)
- Primary completion
- 11 Apr 2019 (actual)
- Study completion
- 30 Jun 2019 (actual)
- First posted
- 6 Feb 2018 (actual)
- Results
- Posted 16 Nov 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Mitochondrial dysfunction has been implicated in heart failure (HF), and is associated with an imbalance in intracellular ratio of reduced nicotinamide-adenine dinucleotide (NADH) to oxidized nicotinamide-adenine dinucleotide (NAD), or the NADH/NAD ratio. In mouse models of HF, we have found that normalization of the NADH/NAD, through supplementation with NAD+ precursors, is associated with improvement in cardiac function. This Study will randomize participants with systolic HF (ejection fraction ≤40%) to treatment with the NAD precursor, nicotinamide riboside (NR) or matching placebo, uptitrated to a final oral dose of 1000mg twice daily, to determine the safety and tolerability of NR in participants with systolic HF.
Detailed description
Aim 1: Determine the safety and tolerability of NR in patients with clinically stable, systolic heart failure (LVEF <40%). To accomplish this Aim:
- a total of 30 participants with clinically stable, systolic heart failure (LVEF <40%) will undergo 2:1 randomization to NR 250mg PO twice daily or matching placebo B) NR (or matching placebo), will be increased weekly by 250mg/dose (500mg/day) to a final dose of 1000mg PO twice daily. Clinic visits with labs bi-weekly during dose escalation will assess HF symptoms and monitor labs [B-type natriuretic peptide (BNP), complete blood count (CBC), glycosylated hemoglobin, alanine aminotransferase (ALT), creatine kinase (CK), insulin/glucose, uric acid, electrolytes, blood urea nitrogen (BUN) and creatinine (Cr).
- to ensure intermediate-term safety and tolerability, participants will continue on their maximum tolerated dose (of NR or placebo) through Study Week 12
Aim 2: Determine whether, at the doses employed, NR and NAD are detectable in whole blood.
Aim 3 (Exploratory): Assess the range of potential effect sizes of NR on HF surrogate endpoints using:
- Six-minute walk tests (6MWTs) at each visit (including Screening) to assess functional capacity B) Echocardiography at Baseline and Week 12 to assess LV systolic function (by real-time, 3D echocardiography) and diastolic function (by integrated Doppler and tissue Doppler imaging)
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- 2:1 randomization to nicotinamide riboside vs. matching placebo
| Arm | Type | Receives |
|---|---|---|
| Nicotinamide Riboside | Experimental | Dietary Supplement: nicotinamide ribosideNicotinamide riboside will be supplied as 250mg capsules, to be administered orally. The initial dose will be 1 capsule twice daily, followed by weekly up-titration by 1 capsule/dose to a final dose of 4 capsules (1000mg) twice daily at the end of Week 4. Participants will be continued on the final dose up to the final follow up visit (week 12). If, at any step, a dose increase is not tolerated, the maximum previously-tolerated dose will be continued through to week 12. |
| Placebo | Placebo comparator | Drug: PlaceboMatching placebo will be supplied as 250mg capsules, to be administered orally. The initial dose will be 1 capsule twice daily, followed by weekly up-titration by 1 capsule/dose to a final dose of 4 capsules (1000mg) twice daily at the end of Week 4. Participants will be continued on the final dose up to the final follow up visit (week 12). If, at any step, a dose increase is not tolerated, the maximum previously-tolerated dose will be continued through to week 12. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Men and women aged 18 and older with systolic heart failure [left ventricular ejection fraction (LVEF) by standard 2D echocardiography or radionuclide ventriculography of ≤40%] deemed, in the clinical opinion of their treating cardiologist to be non-ischemic or ischemic in origin.
- Clinically stable (no cardiac procedures or hospitalizations for hospitalizations for cardiac causes, including HF, ischemia or arrhythmia) within the previous 3 months
- Ability to undergo study procedures, including scheduled visits, blood draws and six-minute walk test (6MWT)
- Willingness/ability to provide informed consent
Key exclusion criteria (14 listed)
- Heart failure with preserved ejection fraction (LVEF greater than 40%)
- Heart failure due, in the opinion of their treating cardiologist, to etiologies other than non-ischemic or ischemic. Examples of exclusionary heart failure etiologies include primary valvular disease, or infiltrative or inflammatory cardiomyopathies.
- Cardiac surgery, percutaneous coronary intervention (PCI) or cardiac device implantation within the previous 3 months
- Hospitalizations for cardiovascular causes, including heart failure, chest pain, stroke, transient ischemic attack or arrhythmias within the previous 3 months
- Inability to perform Study visits or procedures (e.g., physical inability to perform 6MWT)
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 ribosideAlso: Niagennicotinamide riboside capsule | Dietary supplement | Nicotinamide Riboside |
| Placebomatching placebo capsule | Drug | Placebo |
Primary outcome
Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)
Time frame: up to 12 weeks
Adverse Events
3 secondary outcomes
On-Trial Change in Whole Blood NAD+ Levels
Time frame: Week 12-Week 0
Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment
Time frame: 16 weeks
Effect of NR on Change in Mitochondrial Function (Maximal Oxygen Consumption Rate)
Time frame: Week 12 - Week 0
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Nov 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36644285Wang DD, Airhart SE, Zhou B, Shireman LM, Jiang S, Melendez Rodriguez C, Kirkpatrick JN, Shen DD, Tian R, O'Brien KD. Safety and Tolerability of Nicotinamide Riboside in Heart Failure With Reduced Ejection Fraction. JACC Basic Transl Sci. 2022 Sep 14;7(12):1183-1196. doi: 10.1016/j.jacbts.2022.06.012. eCollection 2022 Dec.
- Individual participant dataSharing planned: Yes. A de-identified, public access database will be made available two years after publication of the primary study results. Data files will be delivered in electronic format, providing meta-data that completely describes the tables, variables and coding. Both the raw data and the primary analysis files will be included. Primary analysis files are a compilation of key variables used to generate the statistical results, to help assure that investigators reach consistent conclusions when analyzing the data to published results. Data, documentation and all other materials will be delivered to NHLBI, as well as a document that fully describes the data, steps taken to de-identify the data, and quality control procedures. A document summarizing data tables and other files that are being delivered and describing the data manipulations applied to the data to assure data anonymity, including an annotated clinical study report providing the database variable names.
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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 Phase 1/2 study testing nicotinamide riboside in people with Heart Failure, Systolic, 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 4 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: finished, as of the sponsor's last update on 16 Nov 2022. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 16 Nov 2022). 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?
Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) (time frame: up to 12 weeks). 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 NCT03423342, 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 16 Nov 2022.