Thiamine Supplementation in Heart Failure: a Pilot Randomized Controlled Crossover Trial (THIAMINE-HF)
Primary Purpose
Heart Failure, Heart Failure With Reduced Ejection Fraction, Thiamine Deficiency
Status
Completed
Phase
Phase 1
Locations
Canada
Study Type
Interventional
Intervention
Thiamine
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Heart Failure focused on measuring thiamine, heart failure, heart failure with reduced ejection fraction, geriatric, thiamin, vitamin b1, congestive heart failure
Eligibility Criteria
Inclusion Criteria:
- Age ≥60
- NYHA class II-IV symptoms
- Recent HF-related admission in past 12 months OR NT-proBNP >600ng/L within 60 days of screening
- LVEF ≤45% on 2D/3D echocardiography or radionuclide angiography (RNA) in the past 12 months (on optimal therapy)
- Medically optimized prior to enrolment with angiotensin converting enzyme inhibitor or angiotensin receptor blocker (± neprilysin inhibitor), β-blocker, and/or aldosterone antagonist at target or maximally tolerated doses.
- Patients must be stable on medications without hospitalization in the past month.
Exclusion Criteria:
- Taking >2.5mg/d of thiamine supplement. Allows standard multivitamin. B complex vitamin not allowed due to high thiamine content.
- Unable to swallow study medication. A placebo swallowing test will take place at screening.
- Clinical indication for thiamine supplementation including symptomatic thiamine deficiency (Wernicke's encephalopathy, severe malnutrition, refeeding syndrome) and heavy alcohol use, >15 standard drinks per week in men and >10 standard drinks per week in women.
- End-stage renal disease on dialysis
- Severe mitral valve disease because this impacts the accuracy of speckle tracking analysis on echocardiography.
- Non-English speaking (unable to complete questionnaires).
- Unable to provide written consent.
- Cognitive impairment without a caregiver administering medications.
- Expected survival <1 year due to non-cardiac disease.
- Expected heart transplantation in <6 months (± left ventricular assistive device).
- Allergies to the ingredients of the study medication or placebo
Sites / Locations
- McMaster University
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Thiamine mononitrate 500mg po daily
Placebo
Arm Description
3 months on thiamine, followed by 6 week washout period, and then 3 months on placebo arm
3 months on placebo, followed by 6 week washout period, and then 3 months on thiamine
Outcomes
Primary Outcome Measures
Recruitment
Number of participants recruited during the study period. This is a feasibility outcome.
Secondary Outcome Measures
Refusal rate
Number of eligible individuals refusing to participate in the research study. This is a feasibility outcome
Retention rate
Number of participants completing the study.
Compliance rate
Proportion of participants with >80% adherence to intervention.
Left ventricular ejection fraction (LVEF)
Echocardiogram measurement of left ventricular ejection fraction.
Peak global longitudinal strain (%)
Speckle tracking echocardiogram measurement of heart contractility. This is a more sensitive measurement of heart function than LVEF.
NT-proBNP
Heart failure biomarker
New York Heart Association (NYHA) class
Heart function symptom grading
Quality of life
Kansas City Cardiomyopathy Questionnaire
HF hospitalizations
Number of hospital stays >24h
HF emergency room visits
Number of hospital visits <24h
Death due to cardiovascular causes
As adjudicated by study committee
Full Information
NCT ID
NCT03228030
First Posted
July 20, 2017
Last Updated
August 30, 2021
Sponsor
Hamilton Health Sciences Corporation
Collaborators
McMaster/St. Peter's Hospital Chair of Aging
1. Study Identification
Unique Protocol Identification Number
NCT03228030
Brief Title
Thiamine Supplementation in Heart Failure: a Pilot Randomized Controlled Crossover Trial
Acronym
THIAMINE-HF
Official Title
Thiamine Supplementation in Heart Failure: a Pilot Randomized Controlled Crossover Trial
Study Type
Interventional
2. Study Status
Record Verification Date
August 2021
Overall Recruitment Status
Completed
Study Start Date
April 2, 2018 (Actual)
Primary Completion Date
April 30, 2021 (Actual)
Study Completion Date
April 30, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hamilton Health Sciences Corporation
Collaborators
McMaster/St. Peter's Hospital Chair of Aging
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Heart failure (HF) is a major cardiovascular disease with increasing prevalence. Thiamine deficiency is common in HF patients. Previous small studies have shown that thiamine supplementation can improve left ventricular systolic function in HF, but larger clinical studies are lacking. Given the ease of supplementation and the potential benefits in HF, we aim to conduct a pilot randomized controlled trial (RCT) using high dose thiamine supplementation in HF patients. The main goal of this pilot study is to determine the feasibility of recruitment for an RCT of thiamine supplementation.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Failure, Heart Failure With Reduced Ejection Fraction, Thiamine Deficiency, Congestive Heart Failure
Keywords
thiamine, heart failure, heart failure with reduced ejection fraction, geriatric, thiamin, vitamin b1, congestive heart failure
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
24 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Thiamine mononitrate 500mg po daily
Arm Type
Experimental
Arm Description
3 months on thiamine, followed by 6 week washout period, and then 3 months on placebo arm
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
3 months on placebo, followed by 6 week washout period, and then 3 months on thiamine
Intervention Type
Dietary Supplement
Intervention Name(s)
Thiamine
Intervention Description
Capsules
Intervention Type
Dietary Supplement
Intervention Name(s)
Placebo
Intervention Description
Identical capsules
Primary Outcome Measure Information:
Title
Recruitment
Description
Number of participants recruited during the study period. This is a feasibility outcome.
Time Frame
11 months
Secondary Outcome Measure Information:
Title
Refusal rate
Description
Number of eligible individuals refusing to participate in the research study. This is a feasibility outcome
Time Frame
11 months
Title
Retention rate
Description
Number of participants completing the study.
Time Frame
11 months
Title
Compliance rate
Description
Proportion of participants with >80% adherence to intervention.
Time Frame
11 months
Title
Left ventricular ejection fraction (LVEF)
Description
Echocardiogram measurement of left ventricular ejection fraction.
Time Frame
3 months
Title
Peak global longitudinal strain (%)
Description
Speckle tracking echocardiogram measurement of heart contractility. This is a more sensitive measurement of heart function than LVEF.
Time Frame
3 months
Title
NT-proBNP
Description
Heart failure biomarker
Time Frame
3 months
Title
New York Heart Association (NYHA) class
Description
Heart function symptom grading
Time Frame
3 months
Title
Quality of life
Description
Kansas City Cardiomyopathy Questionnaire
Time Frame
3 months
Title
HF hospitalizations
Description
Number of hospital stays >24h
Time Frame
7.5 months
Title
HF emergency room visits
Description
Number of hospital visits <24h
Time Frame
7.5 months
Title
Death due to cardiovascular causes
Description
As adjudicated by study committee
Time Frame
7.5 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age ≥60
NYHA class II-IV symptoms
Recent HF-related admission in past 12 months OR NT-proBNP >600ng/L within 60 days of screening
LVEF ≤45% on 2D/3D echocardiography or radionuclide angiography (RNA) in the past 12 months (on optimal therapy)
Medically optimized prior to enrolment with angiotensin converting enzyme inhibitor or angiotensin receptor blocker (± neprilysin inhibitor), β-blocker, and/or aldosterone antagonist at target or maximally tolerated doses.
Patients must be stable on medications without hospitalization in the past month.
Exclusion Criteria:
Taking >2.5mg/d of thiamine supplement. Allows standard multivitamin. B complex vitamin not allowed due to high thiamine content.
Unable to swallow study medication. A placebo swallowing test will take place at screening.
Clinical indication for thiamine supplementation including symptomatic thiamine deficiency (Wernicke's encephalopathy, severe malnutrition, refeeding syndrome) and heavy alcohol use, >15 standard drinks per week in men and >10 standard drinks per week in women.
End-stage renal disease on dialysis
Severe mitral valve disease because this impacts the accuracy of speckle tracking analysis on echocardiography.
Non-English speaking (unable to complete questionnaires).
Unable to provide written consent.
Cognitive impairment without a caregiver administering medications.
Expected survival <1 year due to non-cardiac disease.
Expected heart transplantation in <6 months (± left ventricular assistive device).
Allergies to the ingredients of the study medication or placebo
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Eric KC Wong, MD FRCPC
Organizational Affiliation
McMaster University
Official's Role
Principal Investigator
Facility Information:
Facility Name
McMaster University
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8N3Z5
Country
Canada
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Citations:
PubMed Identifier
30258648
Citation
Wong EKC, Lee JY, Leong DP, Mbuagbaw L, Yousuf H, Keen S, Straus SE, Patterson CJ, Demers C. Thiamine versus placebo in older heart failure patients: study protocol for a randomized controlled crossover feasibility trial (THIAMINE-HF). Pilot Feasibility Stud. 2018 Sep 20;4:149. doi: 10.1186/s40814-018-0342-0. eCollection 2018.
Results Reference
derived
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Thiamine Supplementation in Heart Failure: a Pilot Randomized Controlled Crossover Trial
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