Thiamine Supplementation in Heart Failure: a Pilot Randomized Controlled Crossover Trial (THIAMINE-HF)

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.

Study Overview

• Status: Completed
• Conditions: Heart Failure; Congestive Heart Failure; Heart Failure With Reduced Ejection Fraction; Thiamine Deficiency
• Intervention / Treatment: Dietary supplement: Thiamine; Dietary supplement: Placebo

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8N3Z5
      • McMaster University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Thiamine mononitrate 500mg po daily; 3 months on thiamine, followed by 6 week washout period, and then 3 months on placebo arm	Dietary supplement: Thiamine; Capsules
PLACEBO_COMPARATOR: Placebo; 3 months on placebo, followed by 6 week washout period, and then 3 months on thiamine	Dietary supplement: Placebo; Identical capsules

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

Collaborators and Investigators

• Sponsor: Hamilton Health Sciences Corporation
• Collaborators: McMaster/St. Peter's Hospital Chair of Aging
• Investigators: Principal Investigator: Eric KC Wong, MD FRCPC, McMaster University

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 2, 2018
• Primary Completion (ACTUAL): April 30, 2021
• Study Completion (ACTUAL): April 30, 2021

Study Registration Dates

• First Submitted: July 20, 2017
• First Submitted That Met QC Criteria: July 21, 2017
• First Posted (ACTUAL): July 24, 2017

Study Record Updates

• Last Update Posted (ACTUAL): August 31, 2021
• Last Update Submitted That Met QC Criteria: August 30, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: heart failure; geriatric; thiamine; congestive heart failure; thiamin; vitamin b1; heart failure with reduced ejection fraction
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Nutrition Disorders; Avitaminosis; Deficiency Diseases; Malnutrition; Vitamin B Deficiency; Heart Failure; Thiamine Deficiency; Beriberi; Physiological Effects of Drugs; Micronutrients; Vitamins; Vitamin B Complex; Thiamine
• Other Study ID Numbers: 15-387

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• 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