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A Trial of Thiamin Supplementation in Patients With Heart Failure

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00959075
Recruitment Status : Completed
First Posted : August 14, 2009
Last Update Posted : February 27, 2018
Heart and Stroke Foundation of Ontario
Information provided by (Responsible Party):
Unity Health Toronto

Brief 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. 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.

Condition or disease Intervention/treatment Phase
Heart Failure Dietary Supplement: Vitamin B1 Dietary Supplement: Placebo Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 70 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized Controlled Trial of the Effect of Thiamin Supplementation on Heart Function in Ambulatory Patients With Heart Failure
Study Start Date : September 2009
Actual Primary Completion Date : November 2015
Actual Study Completion Date : November 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Failure

Arm Intervention/treatment
Experimental: Oral thiamin supplementation
Vitamin B1 (Oral thiamin) 100mg BID for 6 months
Dietary Supplement: Vitamin B1
100 mg Twice a day
Other Name: Jamieson - Thiamin Mononitrate

Placebo Comparator: Sugar pill
oral placebo 1 tablet BID for 6 months
Dietary Supplement: Placebo
Sugar pill

Primary Outcome Measures :
  1. Left ventricular ejection fraction measured by CMR or 3D echo at 6 months [ Time Frame: 6 months ]

Secondary Outcome Measures :
  1. LV volume, regional function as measure by CMR tagging [ Time Frame: 6 months ]
  2. Exercise tolerance - distance walked in the standard six-minute walk test [ Time Frame: 6 months ]
  3. Levels of circulating BNP, norepinephrine and F2-isoprostanes [ Time Frame: 6 months ]
  4. Scores on the Living with Heart Failure quality of life instrument [ Time Frame: 6 months ]
  5. Prevalence of TD in an ambulatory HF population [ Time Frame: 6 months ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

  • 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
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00959075

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Canada, Ontario
Niagara North Family Health Team
St. Catharines, Ontario, Canada, L2R 1R5
Sponsors and Collaborators
Unity Health Toronto
Heart and Stroke Foundation of Ontario
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Principal Investigator: Mary E. Keith, PhD, RD Unity Health Toronto
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Unity Health Toronto Identifier: NCT00959075    
Other Study ID Numbers: NA6617
First Posted: August 14, 2009    Key Record Dates
Last Update Posted: February 27, 2018
Last Verified: February 2018
Keywords provided by Unity Health Toronto:
Thiamin supplementation
Thiamin deficiency
Heart failure
Improve heart function
Vitamin B1 supplementation
Additional relevant MeSH terms:
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Heart Failure
Heart Diseases
Cardiovascular Diseases
Physiological Effects of Drugs
Vitamin B Complex