A Trial of Thiamin Supplementation in Patients With Heart Failure
|ClinicalTrials.gov Identifier: NCT00959075|
Recruitment Status : Completed
First Posted : August 14, 2009
Last Update Posted : December 2, 2015
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|
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 Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||70 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|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|
|Primary Completion Date :||November 2015|
|Study Completion Date :||November 2015|
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
- Left ventricular ejection fraction measured by CMR or 3D echo at 6 months [ Time Frame: 6 months ]
- 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 ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00959075
|St. Michael's Hospital|
|Toronto, Ontario, Canada, M5B 1W8|
|Principal Investigator:||Mary E. Keith, PhD, RD||St. Michael's Hospital, Toronto|