A Trial of Thiamin Supplementation in Patients With Heart Failure

February 26, 2018 updated by: Unity Health Toronto

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.

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

70

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • St. Catharines, Ontario, Canada, L2R 1R5
        • Niagara North Family Health Team

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / 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 Names:
  • Jamieson - Thiamin Mononitrate
Placebo Comparator: Sugar pill
oral placebo 1 tablet BID for 6 months
Dietary supplement: Placebo
Sugar pill

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Left ventricular ejection fraction measured by CMR or 3D echo at 6 months
Time Frame: 6 months
6 months

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Unity Health Toronto

Collaborators

Heart and Stroke Foundation of Ontario

Investigators

  • Principal Investigator: Mary E. Keith, PhD, RD, Unity Health Toronto

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2009

Primary Completion (Actual)

November 1, 2015

Study Completion (Actual)

November 1, 2015

Study Registration Dates

First Submitted

August 13, 2009

First Submitted That Met QC Criteria

August 13, 2009

First Posted (Estimate)

August 14, 2009

Study Record Updates

Last Update Posted (Actual)

February 27, 2018

Last Update Submitted That Met QC Criteria

February 26, 2018

Last Verified

February 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NA6617

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Heart Failure

Clinical Trials on Vitamin B1

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Bangladesh

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe