Heart FailurePhase 4NCT00959075
A Trial of Thiamin Supplementation in Patients With Heart Failure
A Phase 4 study testing Vitamin B1 in people with Heart Failure, run by Unity Health Toronto at 1 site in Canada.
Trial summary
Background: Patients with heart failure (HF) are at increased risk of developing thiamin deficiency (TD). Thiamin (vitamin B1) is required for the production of energy and therefore TD may contribute to the energy depletion commonly observed in the failing heart. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Heart Failure
- What is being tested?
- Vitamin B1
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 70 participants
- Where
- 1 siteCanada
- Study dates
- Sep 2009to Nov 2015
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- primary diagnosis of ischemic, dilated, idiopathic or valvular heart failure characterized by an ejection fraction of < 45% (echocardiography or radionuclide scan)
- have an optimized medication regimen (ACE inhibitor or angiotensin receptor blocker, and beta blocker at target doses, or up-titrated to the maximum doses as tolerated)
- been stable (on current medication regimen with no hospitalizations for acute decompensated heart failure > 2 months) prior to entry into the study
- Exclusion Criteria: Participants will be excluded if they are:
- unable or unwilling to provide informed consent
- have any concurrent condition which would result in thiamin deficiency, namely gastrointestinal disorders, magnesium deficiency, liver disease, thyrotoxicosis, B12 deficiency, folate deficiency, prolonged diarrhoeal disease, dialysis, prolonged fever or infection, recent myocardial infarction, coronary revascularization (percutaneous coronary intervention or coronary artery bypass surgery within 3 months), or renal failure
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- are rapidly deteriorating, who are not on a stable medication regimen (2 months or more) or who have been hospitalized for acute decompensated heart failure in the last 2 months
- are on experimental medications
- are taking vitamin supplements containing thiamin >10mg/day
- consume excessive alcohol (> 3 drinks per day), have a documented history of alcoholism or have documented alcoholic cardiomyopathy
- have permanent atrial fibrillation
- are pregnant or would like to become pregnant
- have a right-to-left, bidirectional, or transient right to left cardiac shunts
- have clinically suspected wet Beri Beri in the opinion of the treating physician
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized Controlled Trial of the Effect of Thiamin Supplementation on Heart Function in Ambulatory Patients With Heart Failure
Background: Patients with heart failure (HF) are at increased risk of developing thiamin deficiency (TD). Thiamin (vitamin B1) is required for the production of energy and therefore TD may contribute to the energy depletion commonly observed in the failing heart. Thiamin supplementation trials to date have shown conflicting results and therefore further studies to explain the impact of thiamin supplementation on HF patients with TD is necessary.
Objective: The purpose of this study is to determine whether thiamin supplementation in an ambulatory cohort of patients with systolic heart failure will provide any benefit in terms of improved heart function, symptoms, exercise capacity, and quality of life.
Read more
Description: Patients involved in the study will be given either thiamin supplements or a matching placebo (pills containing no thiamin) for 6 months. The ability of the heart to pump before and after the supplementation will be measured using cardiac magnetic resonance imaging (MRI)and/or 3D echocardiography.
Relevance: This study will determine whether thiamin supplementation improves cardiac function, exercise tolerance and quality of life. Thiamin supplementation is widely available, inexpensive, and safe. Therefore this trial may have a major impact on the optimal management of the expanding population of heart failure patients.
Read the detailed description
Background: There is now accumulating evidence that patients with heart failure (HF) have a high prevalence of thiamin deficiency (TD). Since thiamin is a key cofactor in the enzyme systems that produce energy from both carbohydrates and fats, TD may contribute to the energy depletion frequently observed in the failing heart. Altered energy reserves with a reduction in myocardial ATP have now been recognized to play a critical role in the development and progression of HF. Therefore, correction of TD may enhance cardiac energy substrate availability and utilization, leading to improvement of ventricular function and symptoms.
Primary Hypothesis: The left ventricular ejection fraction in stable, ambulatory patients with systolic heart failure receiving 6 months of oral thiamin supplementation will be significantly higher in comparison with those receiving a placebo.
Secondary Hypothesis: In heart failure patients oral thiamin supplementation will 1)have favourable effects on ventricular remodelling (reduction in diastolic and systolic volumes) and regional function; 2)reduce neurohormonal stimulation (BNP and norepinephrine) as well as oxidative stress; 3)improve exercise capacity and 4)improve symptoms and quality of life.
Ambulatory patients attending heart failure clinics at Mount Sinai, University Health Network, Trillium Health Centre and St. Michael's Hospital with systolic heart failure (NYHA class II-IV, left ventricular ejection fraction <45%) will be screened for eligibility to participate in our randomized trial. We will randomize seventy eligible patients using a stratified, permuted block randomization scheme, to be given either 100mg BID of thiamin HCl or a matching placebo BID in a 1:1 ratio to be taken for six months. All study personnel will be blinded to treatment assignment.
Participants will have baseline and follow-up visits which include collecting demographic data, history of medication use, symptoms, anthropometrics as well as a physical exam. Left ventricular ejection fraction, volumes, and regional function will be measured using a standardized echocardiogram and cardiac MRI at baseline and after six months of supplementation. At this time, blood markers of thiamin status, oxidative stress (F2 isoprostanes) and neurohormonal activation (norepinephrine and BNP) will also be measured. Participants will also complete a six-minute walk test, a 3-day dietary record, the Living with Heart Failure quality of life instrument and a 24-hour urine collection (to measure urinary thiamin excretion) at both baseline and follow-up visits. Compliance will be measured using returned pill counts and verified by measuring plasma thiamin levels which respond rapidly to thiamin supplementation.
- Conditions
- Heart Failure
- Being tested
- Vitamin B1, Placebo
- Keywords
- Thiamin supplementation, Thiamin deficiency, Heart failure, Improve heart function, Vitamin B1 supplementation
- Medical subject headings
- Heart Failure, Beriberi
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vitamin B1Dietary supplement
Also called Jamieson - Thiamin Mononitrate
100 mg Twice a day
PlaceboDietary supplement
Sugar pill
| Study group | Role | What they receive |
|---|---|---|
| Oral thiamin supplementation | Experimental | Vitamin B1 (Oral thiamin) 100mg BID for 6 months Receives: Dietary Supplement: Vitamin B1 |
| Sugar pill | Placebo comparator | oral placebo 1 tablet BID for 6 months Receives: Dietary Supplement: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Left ventricular ejection fraction measured by CMR or 3D echo at 6 months
Measured: 6 months
Secondary outcomes (5)
LV volume, regional function as measure by CMR tagging
Measured: 6 months
Exercise tolerance - distance walked in the standard six-minute walk test
Measured: 6 months
Levels of circulating BNP, norepinephrine and F2-isoprostanes
Measured: 6 months
Scores on the Living with Heart Failure quality of life instrument
Measured: 6 months
Prevalence of TD in an ambulatory HF population
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Aug 2009 (estimated)
- Study startSep 2009
- Primary completionNov 2015
- Study completionNov 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- More trials run by Unity Health TorontoThe 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 70 participants (actual)
Sponsor and investigators
- Lead sponsor
- Unity Health Toronto
- Sponsor type
- University, hospital or other
- Collaborators
- Heart and Stroke Foundation of Ontario
- Responsible party
- Sponsor
- Investigators
- Mary E. Keith, PhD, RD, Principal investigator, Unity Health Toronto
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00959075
- Sponsor's protocol ID
- NA6617
- Status last verified
- Feb 2018
- First submitted
- 13 Aug 2009
- Last updated
- 27 Feb 2018
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Keith M, Quach S, Ahmed M, Azizi-Namini P, Al-Hesayen A, Azevedo E, James R, Leong-Poi H, Ong G, Desjardins S, Lee PJ, Ravamehr-Lake D, Yan AT. Thiamin supplementation does not improve left ventricular ejection fraction in ambulatory heart failure patients: a randomized controlled trial. Am J Clin Nutr. 2019 Dec 1;110(6):1287-1295. doi: 10.1093/ajcn/nqz192.
PubMed 31504093
Study at a glance
From the registry record, last updated by the sponsor on 27 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Controlled Trial of the Effect of Thiamin Supplementation on Heart Function in Ambulatory Patients With Heart Failure
- ClinicalTrials.gov ID
- NCT00959075
- Acronym / sponsor ID
- NA6617
- Conditions
- Heart Failure
- Keywords
- Thiamin supplementation, Thiamin deficiency, Heart failure, Improve heart function, Vitamin B1 supplementation
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 70 participants (actual)
- Lead sponsor
- Unity Health TorontoUniversity, hospital or other
- Collaborators
- Heart and Stroke Foundation of Ontario
- Study start
- Sep 2009
- Primary completion
- Nov 2015 (actual)
- Study completion
- Nov 2015 (actual)
- First posted
- 14 Aug 2009 (estimated)
- 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.
Background: Patients with heart failure (HF) are at increased risk of developing thiamin deficiency (TD). Thiamin (vitamin B1) is required for the production of energy and therefore TD may contribute to the energy depletion commonly observed in the failing heart. Thiamin supplementation trials to date have shown conflicting results and therefore further studies to explain the impact of thiamin supplementation on HF patients with TD is necessary.
Objective: The purpose of this study is to determine whether thiamin supplementation in an ambulatory cohort of patients with systolic heart failure will provide any benefit in terms of improved heart function, symptoms, exercise capacity, and quality of life.
Description: Patients involved in the study will be given either thiamin supplements or a matching placebo (pills containing no thiamin) for 6 months. The ability of the heart to pump before and after the supplementation will be measured using cardiac magnetic resonance imaging (MRI)and/or 3D echocardiography.
Relevance: This study will determine whether thiamin supplementation improves cardiac function, exercise tolerance and quality of life. Thiamin supplementation is widely available, inexpensive, and safe. Therefore this trial may have a major impact on the optimal management of the expanding population of heart failure patients.
Detailed description
Background: There is now accumulating evidence that patients with heart failure (HF) have a high prevalence of thiamin deficiency (TD). Since thiamin is a key cofactor in the enzyme systems that produce energy from both carbohydrates and fats, TD may contribute to the energy depletion frequently observed in the failing heart. Altered energy reserves with a reduction in myocardial ATP have now been recognized to play a critical role in the development and progression of HF. Therefore, correction of TD may enhance cardiac energy substrate availability and utilization, leading to improvement of ventricular function and symptoms.
Primary Hypothesis: The left ventricular ejection fraction in stable, ambulatory patients with systolic heart failure receiving 6 months of oral thiamin supplementation will be significantly higher in comparison with those receiving a placebo.
Secondary Hypothesis: In heart failure patients oral thiamin supplementation will 1)have favourable effects on ventricular remodelling (reduction in diastolic and systolic volumes) and regional function; 2)reduce neurohormonal stimulation (BNP and norepinephrine) as well as oxidative stress; 3)improve exercise capacity and 4)improve symptoms and quality of life.
Ambulatory patients attending heart failure clinics at Mount Sinai, University Health Network, Trillium Health Centre and St. Michael's Hospital with systolic heart failure (NYHA class II-IV, left ventricular ejection fraction <45%) will be screened for eligibility to participate in our randomized trial. We will randomize seventy eligible patients using a stratified, permuted block randomization scheme, to be given either 100mg BID of thiamin HCl or a matching placebo BID in a 1:1 ratio to be taken for six months. All study personnel will be blinded to treatment assignment.
Participants will have baseline and follow-up visits which include collecting demographic data, history of medication use, symptoms, anthropometrics as well as a physical exam. Left ventricular ejection fraction, volumes, and regional function will be measured using a standardized echocardiogram and cardiac MRI at baseline and after six months of supplementation. At this time, blood markers of thiamin status, oxidative stress (F2 isoprostanes) and neurohormonal activation (norepinephrine and BNP) will also be measured. Participants will also complete a six-minute walk test, a 3-day dietary record, the Living with Heart Failure quality of life instrument and a 24-hour urine collection (to measure urinary thiamin excretion) at both baseline and follow-up visits. Compliance will be measured using returned pill counts and verified by measuring plasma thiamin levels which respond rapidly to thiamin supplementation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Oral thiamin supplementation | Experimental | Dietary Supplement: Vitamin B1Vitamin B1 (Oral thiamin) 100mg BID for 6 months |
| Sugar pill | Placebo comparator | Dietary Supplement: Placebooral placebo 1 tablet BID for 6 months |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- primary diagnosis of ischemic, dilated, idiopathic or valvular heart failure characterized by an ejection fraction of < 45% (echocardiography or radionuclide scan)
- have an optimized medication regimen (ACE inhibitor or angiotensin receptor blocker, and beta blocker at target doses, or up-titrated to the maximum doses as tolerated)
- been stable (on current medication regimen with no hospitalizations for acute decompensated heart failure > 2 months) prior to entry into the study
- unable or unwilling to provide informed consent
- have any concurrent condition which would result in thiamin deficiency, namely gastrointestinal disorders, magnesium deficiency, liver disease, thyrotoxicosis, B12 deficiency, folate deficiency, prolonged diarrhoeal disease, dialysis, prolonged fever or infection, recent myocardial infarction, coronary revascularization (percutaneous coronary intervention or coronary artery bypass surgery within 3 months), or renal failure
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| Vitamin B1Also: Jamieson - Thiamin Mononitrate100 mg Twice a day | Dietary supplement | Oral thiamin supplementation |
| PlaceboSugar pill | Dietary supplement | Sugar pill |
Primary outcome
Left ventricular ejection fraction measured by CMR or 3D echo at 6 months
Time frame: 6 months
5 secondary outcomes
LV volume, regional function as measure by CMR tagging
Time frame: 6 months
Exercise tolerance - distance walked in the standard six-minute walk test
Time frame: 6 months
Levels of circulating BNP, norepinephrine and F2-isoprostanes
Time frame: 6 months
Scores on the Living with Heart Failure quality of life instrument
Time frame: 6 months
Prevalence of TD in an ambulatory HF population
Time frame: 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Feb 2018.
- Derived from this study: PubMed 31504093Keith M, Quach S, Ahmed M, Azizi-Namini P, Al-Hesayen A, Azevedo E, James R, Leong-Poi H, Ong G, Desjardins S, Lee PJ, Ravamehr-Lake D, Yan AT. Thiamin supplementation does not improve left ventricular ejection fraction in ambulatory heart failure patients: a randomized controlled trial. Am J Clin Nutr. 2019 Dec 1;110(6):1287-1295. doi: 10.1093/ajcn/nqz192.
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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.
Mary E. Keith, PhD, RD principal investigator
Unity Health Toronto
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Vitamin B1 in people with Heart Failure, run by Unity Health Toronto at 1 site in Canada.
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 14 inclusion and 0 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 27 Feb 2018. 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 Canada. 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?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Left ventricular ejection fraction measured by CMR or 3D echo at 6 months (time frame: 6 months). 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 NCT00959075, 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 27 Feb 2018.