Thiamine Supplementation in Heart Failure: a Pilot Randomized Controlled Crossover Trial

Study Overview
=================
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.

Official Title
-----------------
Thiamine Supplementation in Heart Failure: a Pilot Randomized Controlled Crossover Trial

Conditions
-----------------
Heart Failure, Heart Failure With Reduced Ejection Fraction, Thiamine Deficiency, Congestive Heart Failure

Intervention / Treatment
-----------------
* Dietary Supplement: Thiamine
* Dietary Supplement: Placebo


Participation Criteria
=================
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

Ages Eligible for Study
-----------------
Minimum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Thiamine mononitrate 500mg po daily<br>3 months on thiamine, followed by 6 week washout period, and then 3 months on placebo arm | Dietary Supplement: Thiamine<br>* Capsules<br>|
| Placebo Comparator: Placebo<br>3 months on placebo, followed by 6 week washout period, and then 3 months on thiamine | Dietary Supplement: Placebo<br>* Identical capsules<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recruitment | Number of participants recruited during the study period. This is a feasibility outcome. | 11 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Refusal rate | Number of eligible individuals refusing to participate in the research study. This is a feasibility outcome | 11 months | 
| Retention rate | Number of participants completing the study. | 11 months | 
| Compliance rate | Proportion of participants with >80% adherence to intervention. | 11 months | 
| Left ventricular ejection fraction (LVEF) | Echocardiogram measurement of left ventricular ejection fraction. | 3 months | 
| Peak global longitudinal strain (%) | Speckle tracking echocardiogram measurement of heart contractility. This is a more sensitive measurement of heart function than LVEF. | 3 months | 
| NT-proBNP | Heart failure biomarker | 3 months | 
| New York Heart Association (NYHA) class | Heart function symptom grading | 3 months | 
| Quality of life | Kansas City Cardiomyopathy Questionnaire | 3 months | 
| HF hospitalizations | Number of hospital stays >24h | 7.5 months | 
| HF emergency room visits | Number of hospital visits <24h | 7.5 months | 
| Death due to cardiovascular causes | As adjudicated by study committee | 7.5 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
thiamin, thiamine, heart failure, heart failure with reduced ejection fraction, geriatric, vitamin b1, congestive heart failure