<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03228030</url>
  </required_header>
  <id_info>
    <org_study_id>15-387</org_study_id>
    <nct_id>NCT03228030</nct_id>
  </id_info>
  <brief_title>Thiamine Supplementation in Heart Failure: a Pilot Randomized Controlled Crossover Trial</brief_title>
  <acronym>THIAMINE-HF</acronym>
  <official_title>Thiamine Supplementation in Heart Failure: a Pilot Randomized Controlled Crossover Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hamilton Health Sciences Corporation</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>McMaster/St. Peter's Hospital Chair of Aging</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>McMaster University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Heart failure (HF) is a major cardiovascular disease with increasing prevalence. Thiamine&#xD;
      deficiency is common in HF patients. Previous small studies have shown that thiamine&#xD;
      supplementation can improve left ventricular systolic function in HF, but larger clinical&#xD;
      studies are lacking. Given the ease of supplementation and the potential benefits in HF, we&#xD;
      aim to conduct a pilot randomized controlled trial (RCT) using high dose thiamine&#xD;
      supplementation in HF patients. The main goal of this pilot study is to determine the&#xD;
      feasibility of recruitment for an RCT of thiamine supplementation.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 2, 2018</start_date>
  <completion_date type="Actual">April 30, 2021</completion_date>
  <primary_completion_date type="Actual">April 30, 2021</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Recruitment</measure>
    <time_frame>11 months</time_frame>
    <description>Number of participants recruited during the study period. This is a feasibility outcome.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Refusal rate</measure>
    <time_frame>11 months</time_frame>
    <description>Number of eligible individuals refusing to participate in the research study. This is a feasibility outcome</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Retention rate</measure>
    <time_frame>11 months</time_frame>
    <description>Number of participants completing the study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Compliance rate</measure>
    <time_frame>11 months</time_frame>
    <description>Proportion of participants with &gt;80% adherence to intervention.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Left ventricular ejection fraction (LVEF)</measure>
    <time_frame>3 months</time_frame>
    <description>Echocardiogram measurement of left ventricular ejection fraction.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Peak global longitudinal strain (%)</measure>
    <time_frame>3 months</time_frame>
    <description>Speckle tracking echocardiogram measurement of heart contractility. This is a more sensitive measurement of heart function than LVEF.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>NT-proBNP</measure>
    <time_frame>3 months</time_frame>
    <description>Heart failure biomarker</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>New York Heart Association (NYHA) class</measure>
    <time_frame>3 months</time_frame>
    <description>Heart function symptom grading</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life</measure>
    <time_frame>3 months</time_frame>
    <description>Kansas City Cardiomyopathy Questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>HF hospitalizations</measure>
    <time_frame>7.5 months</time_frame>
    <description>Number of hospital stays &gt;24h</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>HF emergency room visits</measure>
    <time_frame>7.5 months</time_frame>
    <description>Number of hospital visits &lt;24h</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Death due to cardiovascular causes</measure>
    <time_frame>7.5 months</time_frame>
    <description>As adjudicated by study committee</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">24</enrollment>
  <condition>Heart Failure</condition>
  <condition>Heart Failure With Reduced Ejection Fraction</condition>
  <condition>Thiamine Deficiency</condition>
  <condition>Congestive Heart Failure</condition>
  <arm_group>
    <arm_group_label>Thiamine mononitrate 500mg po daily</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>3 months on thiamine, followed by 6 week washout period, and then 3 months on placebo arm</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>3 months on placebo, followed by 6 week washout period, and then 3 months on thiamine</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Thiamine</intervention_name>
    <description>Capsules</description>
    <arm_group_label>Thiamine mononitrate 500mg po daily</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Identical capsules</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age ≥60&#xD;
&#xD;
          -  NYHA class II-IV symptoms&#xD;
&#xD;
          -  Recent HF-related admission in past 12 months OR NT-proBNP &gt;600ng/L within 60 days of&#xD;
             screening&#xD;
&#xD;
          -  LVEF ≤45% on 2D/3D echocardiography or radionuclide angiography (RNA) in the past 12&#xD;
             months (on optimal therapy)&#xD;
&#xD;
          -  Medically optimized prior to enrolment with angiotensin converting enzyme inhibitor or&#xD;
             angiotensin receptor blocker (± neprilysin inhibitor), β-blocker, and/or aldosterone&#xD;
             antagonist at target or maximally tolerated doses.&#xD;
&#xD;
          -  Patients must be stable on medications without hospitalization in the past month.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Taking &gt;2.5mg/d of thiamine supplement. Allows standard multivitamin. B complex&#xD;
             vitamin not allowed due to high thiamine content.&#xD;
&#xD;
          -  Unable to swallow study medication. A placebo swallowing test will take place at&#xD;
             screening.&#xD;
&#xD;
          -  Clinical indication for thiamine supplementation including symptomatic thiamine&#xD;
             deficiency (Wernicke's encephalopathy, severe malnutrition, refeeding syndrome) and&#xD;
             heavy alcohol use, &gt;15 standard drinks per week in men and &gt;10 standard drinks per&#xD;
             week in women.&#xD;
&#xD;
          -  End-stage renal disease on dialysis&#xD;
&#xD;
          -  Severe mitral valve disease because this impacts the accuracy of speckle tracking&#xD;
             analysis on echocardiography.&#xD;
&#xD;
          -  Non-English speaking (unable to complete questionnaires).&#xD;
&#xD;
          -  Unable to provide written consent.&#xD;
&#xD;
          -  Cognitive impairment without a caregiver administering medications.&#xD;
&#xD;
          -  Expected survival &lt;1 year due to non-cardiac disease.&#xD;
&#xD;
          -  Expected heart transplantation in &lt;6 months (± left ventricular assistive device).&#xD;
&#xD;
          -  Allergies to the ingredients of the study medication or placebo&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>60 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Eric KC Wong, MD FRCPC</last_name>
    <role>Principal Investigator</role>
    <affiliation>McMaster University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>McMaster University</name>
      <address>
        <city>Hamilton</city>
        <state>Ontario</state>
        <zip>L8N3Z5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>August 2021</verification_date>
  <study_first_submitted>July 20, 2017</study_first_submitted>
  <study_first_submitted_qc>July 21, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 24, 2017</study_first_posted>
  <last_update_submitted>August 30, 2021</last_update_submitted>
  <last_update_submitted_qc>August 30, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">August 31, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>thiamine</keyword>
  <keyword>heart failure</keyword>
  <keyword>heart failure with reduced ejection fraction</keyword>
  <keyword>geriatric</keyword>
  <keyword>thiamin</keyword>
  <keyword>vitamin b1</keyword>
  <keyword>congestive heart failure</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Heart Failure</mesh_term>
    <mesh_term>Thiamine Deficiency</mesh_term>
    <mesh_term>Beriberi</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Thiamine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03228030
org study id: 15-387
nct id: NCT03228030
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
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.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Recruitment
time frame: 11 months
description: Number of participants recruited during the study period. This is a feasibility outcome.
measure: Refusal rate
time frame: 11 months
description: Number of eligible individuals refusing to participate in the research study. This is a feasibility outcome
measure: Retention rate
time frame: 11 months
description: Number of participants completing the study.
measure: Compliance rate
time frame: 11 months
description: Proportion of participants with >80% adherence to intervention.
measure: Left ventricular ejection fraction (LVEF)
time frame: 3 months
description: Echocardiogram measurement of left ventricular ejection fraction.
measure: Peak global longitudinal strain (%)
time frame: 3 months
description: Speckle tracking echocardiogram measurement of heart contractility. This is a more sensitive measurement of heart function than LVEF.
measure: NT-proBNP
time frame: 3 months
description: Heart failure biomarker
measure: New York Heart Association (NYHA) class
time frame: 3 months
description: Heart function symptom grading
measure: Quality of life
time frame: 3 months
description: Kansas City Cardiomyopathy Questionnaire
measure: HF hospitalizations
time frame: 7.5 months
description: Number of hospital stays >24h
measure: HF emergency room visits
time frame: 7.5 months
description: Number of hospital visits <24h
measure: Death due to cardiovascular causes
time frame: 7.5 months
description: As adjudicated by study committee
arm group label: Thiamine mononitrate 500mg po daily
arm group type: Experimental
description: 3 months on thiamine, followed by 6 week washout period, and then 3 months on placebo arm
arm group label: Placebo
arm group type: Placebo Comparator
description: 3 months on placebo, followed by 6 week washout period, and then 3 months on thiamine
intervention type: Dietary Supplement
intervention name: Thiamine
description: Capsules
arm group label: Thiamine mononitrate 500mg po daily
intervention type: Dietary Supplement
intervention name: Placebo
description: Identical capsules
arm group label: Placebo
criteria: 
gender: All
minimum age: 60 Years
maximum age: N/A
healthy volunteers: No
last name: Eric KC Wong, MD FRCPC
role: Principal Investigator
affiliation: McMaster University
facility: 
country: Canada
responsible party type: Sponsor
mesh term: Heart Failure
mesh term: Thiamine Deficiency
mesh term: Beriberi
mesh term: Thiamine
sharing ipd: Undecided