Trial record 3 of 18 for:    Open Studies | "Thiamine"

A Trial of Thiamin Supplementation in Patients With Heart Failure

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2012 by St. Michael's Hospital, Toronto
Sponsor:
Collaborator:
Heart and Stroke Foundation of Ontario
Information provided by (Responsible Party):
mary keith, St. Michael's Hospital, Toronto
ClinicalTrials.gov Identifier:
NCT00959075
First received: August 13, 2009
Last updated: December 21, 2012
Last verified: December 2012
  Purpose

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 Intervention Phase
Heart Failure
Dietary Supplement: Vitamin B1
Dietary Supplement: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by St. Michael's Hospital, Toronto:

Primary Outcome Measures:
  • Left ventricular ejection fraction measured by CMR or 3D echo at 6 months [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • LV volume, regional function as measure by CMR tagging [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Exercise tolerance - distance walked in the standard six-minute walk test [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Levels of circulating BNP, norepinephrine and F2-isoprostanes [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Scores on the Living with Heart Failure quality of life instrument [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Prevalence of TD in an ambulatory HF population [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 70
Study Start Date: September 2009
Estimated Study Completion Date: September 2013
Estimated Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Oral thiamin supplementation Dietary Supplement: Vitamin B1
100 mg Twice a day
Other Name: Jamieson - Thiamin Mononitrate
Placebo Comparator: Sugar pill Dietary Supplement: Placebo
Sugar pill

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00959075

Contacts
Contact: Mary E. Keith, PhD, RD 416-864-5551 keithm@smh.ca

Locations
Canada, Ontario
St. Michael's Hospital Recruiting
Toronto, Ontario, Canada, M5B 1W8
Contact: Mary E. Keith, PhD, RD    416-864-5551    keithm@smh.ca   
Contact: Andrew T. Yan       yanA@smh.ca   
Principal Investigator: Mary E. Keith, PhD, RD         
Sub-Investigator: Andrew T. Yan         
Sub-Investigator: Peter P. Liu         
Sponsors and Collaborators
St. Michael's Hospital, Toronto
Heart and Stroke Foundation of Ontario
Investigators
Principal Investigator: Mary E. Keith, PhD, RD St. Michael's Hospital, Toronto
  More Information

No publications provided

Responsible Party: mary keith, Coordinator of Nutrition and Dietetic Education/Research, St. Michael's Hospital, Toronto
ClinicalTrials.gov Identifier: NCT00959075     History of Changes
Other Study ID Numbers: NA6617
Study First Received: August 13, 2009
Last Updated: December 21, 2012
Health Authority: Canada: Health Canada

Keywords provided by St. Michael's Hospital, Toronto:
Thiamin supplementation
Thiamin deficiency
Heart failure
Improve heart function
Vitamin B1 supplementation

Additional relevant MeSH terms:
Heart Failure
Cardiovascular Diseases
Heart Diseases
Thiamine
Vitamin B Complex
Vitamins
Growth Substances
Micronutrients
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 20, 2014