<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/NCT03779646</url>
  </required_header>
  <id_info>
    <org_study_id>PekingUMCH-DMD</org_study_id>
    <nct_id>NCT03779646</nct_id>
  </id_info>
  <brief_title>Bisoprolol in DMD Early Cardiomyopathy</brief_title>
  <official_title>Bisoprolol for Early Cardiomyopathy in Duchenne Muscular Dystrophy: a Randomized, Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Peking Union Medical College Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Natural Science Foundation of China</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Cancer Institute and Hospital, Chinese Academy of Medical Sciences</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Peking Union Medical College Hospital</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study aimed to use cardiac magnetic resonance imaging (CMR) to evaluate the efficacy and&#xD;
      safety of bisoprolol therapy for boys with Duchenne muscular dystrophy(DMD) and preserved&#xD;
      ejection fraction. On top of angiotensin-converting enzyme inhibitor (ACEI) , half of the&#xD;
      participants will receive bisoprolol in combination, while the other half will not receive&#xD;
      any beta-blocker.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      By the age of 20 years, almost all the patients with Duchenne muscular dystrophy(DMD) have&#xD;
      experienced dilated cardiomyopathy (DCM), a condition that contributes significantly to their&#xD;
      morbidity and mortality. Studies have shown ACEI to be an effective therapy for DMD boys with&#xD;
      early cardiomyopathy. Although bisoprolol has been demonstrated as an effective neurohumoral&#xD;
      drug for adult patients with DCM, few data exist concerning its safety and efficacy for the&#xD;
      patients with DMD. The investigators hypothesize that the treatment with bisoprolol in&#xD;
      addition to background ACEI therapy for 12 months in participants with DMD and early&#xD;
      myocardial damage evident with late gadolinium enhancement and preserved ejection fraction,&#xD;
      would blunt decline in left ventricular systolic performance.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">January 16, 2019</start_date>
  <completion_date type="Anticipated">July 1, 2024</completion_date>
  <primary_completion_date type="Anticipated">July 1, 2023</primary_completion_date>
  <phase>Phase 2/Phase 3</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>
    <intervention_model_description>This is a randomized, controlled trial.Enrolled participants should receive a kind of ACEI drug for more than 1 month and the dose should be fixed. Then the participants were randomly assigned (1:1) to receive either bisoprolol or not any beta blocker.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
    <masking_description>The investigator, care providers and participants will know whether the participants use the trial drug（bisoprolol） or not. But the outcome assessor who will analysis the results of the cardiac MR and echocardiography images from the participants will be blinded to the grouping situation.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Calculate the change of left ventricle global longitudinal strain in cardiac MR</measure>
    <time_frame>baseline and 12 months</time_frame>
    <description>Calculate the change of left ventricle global longitudinal strain in cardiac MR from baseline to 12months for each patients</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Calculate the change of left ventricular ejection fraction in cardia MR</measure>
    <time_frame>baseline and 12 months</time_frame>
    <description>Calculate the change of left ventricular ejection fraction in cardia MR from baseline to 12months for each patients</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Calculate the change of ventricle late gadolinium enhancement area in cardia MR</measure>
    <time_frame>baseline and 12 months</time_frame>
    <description>Calculate the change of ventricle late gadolinium enhancement area in cardia MR from baseline to 12months for each patients</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Calculate the change of the level of high-sensitivity cardiac troponin I</measure>
    <time_frame>baseline and 6months, 12 months</time_frame>
    <description>Calculate the change of the level of high-sensitivity cardiac troponin I from baseline to 6months and 12months for each patients</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Calculate the change of the level of NT-proBNP</measure>
    <time_frame>baseline and 6months, 12 months</time_frame>
    <description>Calculate the change of the level of NT-proBNP from baseline to 6months and 12months for each patients</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Calculate the change of E/A ratio assessed by echocardiography</measure>
    <time_frame>baseline and 12 months</time_frame>
    <description>Calculate the change of diastolic dysfunction (E/A ratio) assessed by echocardiography from baseline to 12months for each patients</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of the resting heart rate</measure>
    <time_frame>baseline and 6months, 12 months</time_frame>
    <description>Calculate the change of the resting heart rate from baseline to 6months and 12months for each patients</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Number of participants with All cause mortality, cardiac death, or hospitalized due to heart problem</measure>
    <time_frame>12 months</time_frame>
    <description>Number of Subjects with All cause mortality, cardiac death, or hospitalized due to heart problem at the end of study</description>
  </other_outcome>
  <other_outcome>
    <measure>Number of participants with bisoprolol-related adverse events as assessed by the following definition</measure>
    <time_frame>12 months</time_frame>
    <description>Bisoprolol treatment-related adverse events including the dizziness, bradyarrhythmia (resting heart rate lower than 55bpm)，II and III degree atrioventricular block，hypotension</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">42</enrollment>
  <condition>Duchenne Muscular Dystrophy</condition>
  <condition>Cardiomyopathy, Dilated</condition>
  <arm_group>
    <arm_group_label>bisoprolol fumarate</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>In this arm, the participants will receive different dose of bisoprolol fumarate.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>In the control (no beta blocker) group, the patients not taking beta blocker will receive outpatient clinic or video visit every 8 weeks and provide their cardiac symptoms, heart rate, blood pressure and ECG. After 12 months , the patients will repeat cardiac MR besides heart rate, blood pressure, symptoms, ECG,BNP and echocardiography records.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Bisoprolol Fumarate</intervention_name>
    <description>Bisoprolol was initiated at a dose of 1.25 mg every 24hr. At subsequent biweekly visits, the bisoprolol dose was increased 1.25mg progressively until a daily dose of 0.2mg/kg or the maximum tolerated dose (The rest heart rate &lt;75bpm and systolic blood pressure &lt;90mmHg) is achieved. If the participant feel dizziness or the rest heart rate below 60 bpm or systolic blood pressure below 85mmHg or there is any new onset contraindication to bisoprolol, the doctor will decide to return back to the previous dose or stop bisoprolol. Each time the dose is increased, the medication is administered in an outpatient clinic setting, with assessment of the participant's heart rate, blood pressure, symptoms and ECG. Once reach the target dose, the patients will be followed up every 8 weeks in an face-to-face or video visit. After 12 months , the participants will repeat cardiac MR besides heart rate, blood pressure, symptoms, ECG and brain natriuretic peptide(BNP), echocardiography records.</description>
    <arm_group_label>bisoprolol fumarate</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Older than(including) 7 years old&#xD;
&#xD;
          -  A definite diagnosis of DMD with muscle pathology confirming the expression of&#xD;
             dystrophin lower than 5% and/or confirmed mutations in the DMD gene using a clinical&#xD;
             accepted technique that completely defines the mutation.&#xD;
&#xD;
          -  Using ACEI or ARB for more than 1 month&#xD;
&#xD;
          -  Confirmed myocardial damage in one or more left ventricular segments evident by late&#xD;
             gadolinium enhancement and preserved left ventricular systolic function(&gt;45%) by cine&#xD;
             cardiac MR in 45 days&#xD;
&#xD;
          -  Normal renal function&#xD;
&#xD;
          -  Holter and blood pressure shows no contraindication of using bisoprolol&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Having metal implanted in body&#xD;
&#xD;
          -  Having claustrophobia&#xD;
&#xD;
          -  Allergic to gadolinium&#xD;
&#xD;
          -  Complicated with other cardiovascular diseases&#xD;
&#xD;
          -  Medical history or Holter show bradyarrhythmia like II/III degree atrioventricular&#xD;
             block, sick sinus syndrome etc.&#xD;
&#xD;
          -  Systolic blood pressure lower than 90mmHg or rest heart rate lower than 75bpm&#xD;
&#xD;
          -  Having COPD or asthma history&#xD;
&#xD;
          -  Having other complications: tumor, endocrine diseases&#xD;
&#xD;
          -  Having beta blockers therapy&#xD;
&#xD;
          -  Planned operation in the future 12 months&#xD;
&#xD;
          -  Allergic to bisoprolol&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>7 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Guo, Doctor</last_name>
    <phone>+86-010-69155068</phone>
    <email>xiaoxiaoguopumch@163.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Peking Union Medical College Hospital</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Xiaoxiao Guo, Dr.</last_name>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>December 14, 2018</study_first_submitted>
  <study_first_submitted_qc>December 16, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 19, 2018</study_first_posted>
  <last_update_submitted>September 27, 2022</last_update_submitted>
  <last_update_submitted_qc>September 27, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 28, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Peking Union Medical College Hospital</investigator_affiliation>
    <investigator_full_name>Xiaoxiao Guo</investigator_full_name>
    <investigator_title>Associated professor</investigator_title>
  </responsible_party>
  <keyword>Duchenne muscular dystrophy</keyword>
  <keyword>Early cardiomyopathy</keyword>
  <keyword>bisoprolol</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Muscular Dystrophies</mesh_term>
    <mesh_term>Muscular Dystrophy, Duchenne</mesh_term>
    <mesh_term>Cardiomyopathies</mesh_term>
    <mesh_term>Cardiomyopathy, Dilated</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Bisoprolol</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</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/NCT03779646
org study id: PekingUMCH-DMD
nct id: NCT03779646
lead sponsor: 
collaborator: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
This study aimed to use cardiac magnetic resonance imaging (CMR) to evaluate the efficacy and
      safety of bisoprolol therapy for boys with Duchenne muscular dystrophy(DMD) and preserved
      ejection fraction. On top of angiotensin-converting enzyme inhibitor (ACEI) , half of the
      participants will receive bisoprolol in combination, while the other half will not receive
      any beta-blocker.
By the age of 20 years, almost all the patients with Duchenne muscular dystrophy(DMD) have
      experienced dilated cardiomyopathy (DCM), a condition that contributes significantly to their
      morbidity and mortality. Studies have shown ACEI to be an effective therapy for DMD boys with
      early cardiomyopathy. Although bisoprolol has been demonstrated as an effective neurohumoral
      drug for adult patients with DCM, few data exist concerning its safety and efficacy for the
      patients with DMD. The investigators hypothesize that the treatment with bisoprolol in
      addition to background ACEI therapy for 12 months in participants with DMD and early
      myocardial damage evident with late gadolinium enhancement and preserved ejection fraction,
      would blunt decline in left ventricular systolic performance.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: This is a randomized, controlled trial.Enrolled participants should receive a kind of ACEI drug for more than 1 month and the dose should be fixed. Then the participants were randomly assigned (1:1) to receive either bisoprolol or not any beta blocker.
primary purpose: Treatment
masking: Single (Outcomes Assessor)
masking description: The investigator, care providers and participants will know whether the participants use the trial drug（bisoprolol） or not. But the outcome assessor who will analysis the results of the cardiac MR and echocardiography images from the participants will be blinded to the grouping situation.
measure: Calculate the change of left ventricle global longitudinal strain in cardiac MR
time frame: baseline and 12 months
description: Calculate the change of left ventricle global longitudinal strain in cardiac MR from baseline to 12months for each patients
measure: Calculate the change of left ventricular ejection fraction in cardia MR
time frame: baseline and 12 months
description: Calculate the change of left ventricular ejection fraction in cardia MR from baseline to 12months for each patients
measure: Calculate the change of ventricle late gadolinium enhancement area in cardia MR
time frame: baseline and 12 months
description: Calculate the change of ventricle late gadolinium enhancement area in cardia MR from baseline to 12months for each patients
measure: Calculate the change of the level of high-sensitivity cardiac troponin I
time frame: baseline and 6months, 12 months
description: Calculate the change of the level of high-sensitivity cardiac troponin I from baseline to 6months and 12months for each patients
measure: Calculate the change of the level of NT-proBNP
time frame: baseline and 6months, 12 months
description: Calculate the change of the level of NT-proBNP from baseline to 6months and 12months for each patients
measure: Calculate the change of E/A ratio assessed by echocardiography
time frame: baseline and 12 months
description: Calculate the change of diastolic dysfunction (E/A ratio) assessed by echocardiography from baseline to 12months for each patients
measure: Change of the resting heart rate
time frame: baseline and 6months, 12 months
description: Calculate the change of the resting heart rate from baseline to 6months and 12months for each patients
measure: Number of participants with All cause mortality, cardiac death, or hospitalized due to heart problem
time frame: 12 months
description: Number of Subjects with All cause mortality, cardiac death, or hospitalized due to heart problem at the end of study
measure: Number of participants with bisoprolol-related adverse events as assessed by the following definition
time frame: 12 months
description: Bisoprolol treatment-related adverse events including the dizziness, bradyarrhythmia (resting heart rate lower than 55bpm)，II and III degree atrioventricular block，hypotension
arm group label: bisoprolol fumarate
arm group type: Experimental
description: In this arm, the participants will receive different dose of bisoprolol fumarate.
arm group label: Control
arm group type: No Intervention
description: In the control (no beta blocker) group, the patients not taking beta blocker will receive outpatient clinic or video visit every 8 weeks and provide their cardiac symptoms, heart rate, blood pressure and ECG. After 12 months , the patients will repeat cardiac MR besides heart rate, blood pressure, symptoms, ECG,BNP and echocardiography records.
intervention type: Drug
intervention name: Bisoprolol Fumarate
description: Bisoprolol was initiated at a dose of 1.25 mg every 24hr. At subsequent biweekly visits, the bisoprolol dose was increased 1.25mg progressively until a daily dose of 0.2mg/kg or the maximum tolerated dose (The rest heart rate <75bpm and systolic blood pressure <90mmHg) is achieved. If the participant feel dizziness or the rest heart rate below 60 bpm or systolic blood pressure below 85mmHg or there is any new onset contraindication to bisoprolol, the doctor will decide to return back to the previous dose or stop bisoprolol. Each time the dose is increased, the medication is administered in an outpatient clinic setting, with assessment of the participant's heart rate, blood pressure, symptoms and ECG. Once reach the target dose, the patients will be followed up every 8 weeks in an face-to-face or video visit. After 12 months , the participants will repeat cardiac MR besides heart rate, blood pressure, symptoms, ECG and brain natriuretic peptide(BNP), echocardiography records.
arm group label: bisoprolol fumarate
criteria: 
gender: Male
minimum age: 7 Years
maximum age: N/A
healthy volunteers: No
last name: Guo, Doctor
phone: +86-010-69155068
email: xiaoxiaoguopumch@163.com
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Peking Union Medical College Hospital
investigator full name: Xiaoxiao Guo
investigator title: Associated professor
mesh term: Muscular Dystrophies
mesh term: Muscular Dystrophy, Duchenne
mesh term: Cardiomyopathies
mesh term: Cardiomyopathy, Dilated
mesh term: Bisoprolol
sharing ipd: No