<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/NCT01696370</url>
  </required_header>
  <id_info>
    <org_study_id>10/0216</org_study_id>
    <nct_id>NCT01696370</nct_id>
  </id_info>
  <brief_title>Trimetazidine Therapy in Hypertrophic Cardiomyopathy</brief_title>
  <official_title>A Phase 2b Randomised, Double Blind, Placebo-controlled Trial of Trimetazidine Therapy in Patients With Non-obstructive Hypertrophic Cardiomyopathy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University College, London</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>British Heart Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University College, London</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Hypertrophic cardiomyopathy (HCM) is a common inherited heart condition that causes&#xD;
      breathlessness, chest pain and fatigue. There are few treatments available. The investigators&#xD;
      have recently shown that a drug called perhexiline reduced symptoms and improved exercise&#xD;
      capacity in patients with HCM. This change appears to be driven by alterations in myocardial&#xD;
      energy metabolism. The aim of this trial is to test a similar drug, trimetazidine, in a group&#xD;
      of symptomatic patients with non-obstructive HCM.&#xD;
&#xD;
      HYPOTHESIS: trimetazidine will improve symptoms, peak oxygen consumption, cardiac function&#xD;
      and arrhythmia burden in medically refractory symptomatic patients with non-obstructive HCM.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      BACKGROUND:&#xD;
&#xD;
      Hypertrophic cardiomyopathy (HCM) is a common inherited disorder of heart muscle affecting 1&#xD;
      in 500 individuals worldwide. It is associated with arrhythmias, heart failure and sudden&#xD;
      death in young people. In the majority of patients, HCM is caused by mutations in genes&#xD;
      encoding cardiac contractile proteins. It has been hypothesised that excessive sarcomeric&#xD;
      energy consumption is an important and early factor in the pathophysiology of HCM. Therefore&#xD;
      modulation of myocardial metabolism presents a novel target for improving myocardial&#xD;
      performance and symptoms in patients with HCM. Trimetazidine is an anti-anginal agent which&#xD;
      like perhexiline reduces fatty acid oxidation and increases glucose oxidation, thus&#xD;
      increasing the efficiency of energy production. Trimetazidine has been shown to significantly&#xD;
      improve exercise performance in patients with stable angina, ischaemic and non ischaemic&#xD;
      cardiomyopathy, either as monotherapy or in combination with beta-blockers or calcium channel&#xD;
      blockers,&#xD;
&#xD;
      DESIGN: A single centre prospective randomised, double blind, placebo-controlled, trial of&#xD;
      trimetazidine therapy.&#xD;
&#xD;
      DOSING: 20 mg Trimetazidine or Placebo three times daily for three months&#xD;
&#xD;
      METHODS: The following assessments will be made at baseline and after 3 months treatment:&#xD;
      history and physical examination, Minnesota heart failure questionnaire, fasting blood tests,&#xD;
      electrocardiogram, echocardiogram, cardiopulmonary exercise test, six minute walk test, 24&#xD;
      hour ECG Holter monitor.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>April 2012</start_date>
  <completion_date type="Anticipated">April 2014</completion_date>
  <primary_completion_date type="Anticipated">April 2014</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Peak oxygen consumption</measure>
    <time_frame>3 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Left ventricular function</measure>
    <time_frame>3 months</time_frame>
    <description>TDI and 2D strain</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Symptom status</measure>
    <time_frame>3 months</time_frame>
    <description>questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Arrhythmia</measure>
    <time_frame>3 months</time_frame>
    <description>24 Hour Holter</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cardiac biomarkers</measure>
    <time_frame>3 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Exercise capacity</measure>
    <time_frame>3 months</time_frame>
    <description>6 minute walk test</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">90</enrollment>
  <condition>Hypertrophic Cardiomyopathy</condition>
  <arm_group>
    <arm_group_label>Trimetazidine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo capsule</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Trimetazidine</intervention_name>
    <description>Trimetazidine 20mg three times per day for 3 months</description>
    <arm_group_label>Trimetazidine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo capsule</intervention_name>
    <description>one capsule three times per day for 3 months</description>
    <arm_group_label>Placebo capsule</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Non-obstructive hypertrophic cardiomyopathy (gradient &lt;30 mmHg at rest)&#xD;
&#xD;
          -  NYHA (New York Heart Association) Class ≥ 2&#xD;
&#xD;
          -  Peak VO2 (maximal oxygen consumption) ≤80% predicted for age and gender&#xD;
&#xD;
          -  Heart rate &lt; 90/minute at rest&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Diabetes Mellitus&#xD;
&#xD;
          -  Abnormal renal function (GFR&lt;60ml/min) or hepatic impairment&#xD;
&#xD;
          -  Female who is pregnant, lactating or planning pregnancy during the course of the study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Perry M Elliott, MBBS MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University College, London</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Perry M Elliott, MBBS MD</last_name>
    <phone>020 3456 7898</phone>
    <email>p.elliott@ucl.ac.uk</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Caroline J Coats, MBBS</last_name>
    <phone>020 3456 7898</phone>
    <email>c.coats@ucl.ac.uk</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>The Heart Hospital, UCLH</name>
      <address>
        <city>London</city>
        <zip>W1G 8PH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>August 2011</verification_date>
  <study_first_submitted>September 27, 2012</study_first_submitted>
  <study_first_submitted_qc>September 28, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 1, 2012</study_first_posted>
  <last_update_submitted>February 27, 2013</last_update_submitted>
  <last_update_submitted_qc>February 27, 2013</last_update_submitted_qc>
  <last_update_posted type="Estimate">February 28, 2013</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Trimetazidine</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cardiomyopathies</mesh_term>
    <mesh_term>Cardiomyopathy, Hypertrophic</mesh_term>
    <mesh_term>Hypertrophy</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Trimetazidine</mesh_term>
  </intervention_browse>
  <pending_results>
    <submitted>October 9, 2018</submitted>
    <returned>February 21, 2019</returned>
  </pending_results>
  <!-- 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/NCT01696370
org study id: 10/0216
nct id: NCT01696370
lead sponsor: 
collaborator: 
has dmc: Yes
Hypertrophic cardiomyopathy (HCM) is a common inherited heart condition that causes
      breathlessness, chest pain and fatigue. There are few treatments available. The investigators
      have recently shown that a drug called perhexiline reduced symptoms and improved exercise
      capacity in patients with HCM. This change appears to be driven by alterations in myocardial
      energy metabolism. The aim of this trial is to test a similar drug, trimetazidine, in a group
      of symptomatic patients with non-obstructive HCM.

      HYPOTHESIS: trimetazidine will improve symptoms, peak oxygen consumption, cardiac function
      and arrhythmia burden in medically refractory symptomatic patients with non-obstructive HCM.
BACKGROUND:

      Hypertrophic cardiomyopathy (HCM) is a common inherited disorder of heart muscle affecting 1
      in 500 individuals worldwide. It is associated with arrhythmias, heart failure and sudden
      death in young people. In the majority of patients, HCM is caused by mutations in genes
      encoding cardiac contractile proteins. It has been hypothesised that excessive sarcomeric
      energy consumption is an important and early factor in the pathophysiology of HCM. Therefore
      modulation of myocardial metabolism presents a novel target for improving myocardial
      performance and symptoms in patients with HCM. Trimetazidine is an anti-anginal agent which
      like perhexiline reduces fatty acid oxidation and increases glucose oxidation, thus
      increasing the efficiency of energy production. Trimetazidine has been shown to significantly
      improve exercise performance in patients with stable angina, ischaemic and non ischaemic
      cardiomyopathy, either as monotherapy or in combination with beta-blockers or calcium channel
      blockers,

      DESIGN: A single centre prospective randomised, double blind, placebo-controlled, trial of
      trimetazidine therapy.

      DOSING: 20 mg Trimetazidine or Placebo three times daily for three months

      METHODS: The following assessments will be made at baseline and after 3 months treatment:
      history and physical examination, Minnesota heart failure questionnaire, fasting blood tests,
      electrocardiogram, echocardiogram, cardiopulmonary exercise test, six minute walk test, 24
      hour ECG Holter monitor.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Peak oxygen consumption
time frame: 3 months
measure: Left ventricular function
time frame: 3 months
description: TDI and 2D strain
measure: Symptom status
time frame: 3 months
description: questionnaire
measure: Arrhythmia
time frame: 3 months
description: 24 Hour Holter
measure: Cardiac biomarkers
time frame: 3 months
measure: Exercise capacity
time frame: 3 months
description: 6 minute walk test
arm group label: Trimetazidine
arm group type: Active Comparator
arm group label: Placebo capsule
arm group type: Placebo Comparator
intervention type: Drug
intervention name: Trimetazidine
description: Trimetazidine 20mg three times per day for 3 months
arm group label: Trimetazidine
intervention type: Other
intervention name: Placebo capsule
description: one capsule three times per day for 3 months
arm group label: Placebo capsule
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Perry M Elliott, MBBS MD
role: Principal Investigator
affiliation: University College, London
last name: Perry M Elliott, MBBS MD
phone: 020 3456 7898
email: p.elliott@ucl.ac.uk
last name: Caroline J Coats, MBBS
phone: 020 3456 7898
email: c.coats@ucl.ac.uk
facility: 
status: Recruiting
country: United Kingdom
responsible party type: Sponsor
mesh term: Cardiomyopathies
mesh term: Cardiomyopathy, Hypertrophic
mesh term: Hypertrophy
mesh term: Trimetazidine
submitted: October 9, 2018
returned: February 21, 2019