Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Bisoprolol in DMD Early Cardiomyopathy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03779646
Recruitment Status : Recruiting
First Posted : December 18, 2018
Last Update Posted : January 21, 2019
Sponsor:
Collaborators:
National Natural Science Foundation of China
Chinese Academy of Medical Sciences
Information provided by (Responsible Party):
Xiaoxiao Guo, Peking Union Medical College Hospital

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Duchenne Muscular Dystrophy Cardiomyopathy, Dilated Drug: Bisoprolol Fumarate Phase 2 Phase 3

Detailed Description:
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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 42 participants
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.
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.
Primary Purpose: Treatment
Official Title: Bisoprolol for Early Cardiomyopathy in Duchenne Muscular Dystrophy: a Randomized, Controlled Trial
Actual Study Start Date : January 16, 2019
Estimated Primary Completion Date : July 1, 2020
Estimated Study Completion Date : July 1, 2022


Arm Intervention/treatment
Experimental: bisoprolol fumarate
In this arm, the participants will receive different dose of bisoprolol fumarate.
Drug: Bisoprolol Fumarate
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.

No Intervention: Control
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.



Primary Outcome Measures :
  1. Calculate the change of left ventricle global longitudinal strain in cardiac MR [ Time Frame: baseline and 12 months ]
    Calculate the change of left ventricle global longitudinal strain in cardiac MR from baseline to 12months for each patients


Secondary Outcome Measures :
  1. Calculate the change of left ventricular ejection fraction in cardia MR [ Time Frame: baseline and 12 months ]
    Calculate the change of left ventricular ejection fraction in cardia MR from baseline to 12months for each patients

  2. Calculate the change of ventricle late gadolinium enhancement area in cardia MR [ Time Frame: baseline and 12 months ]
    Calculate the change of ventricle late gadolinium enhancement area in cardia MR from baseline to 12months for each patients

  3. Calculate the change of the level of high-sensitivity cardiac troponin I [ Time Frame: baseline and 6months, 12 months ]
    Calculate the change of the level of high-sensitivity cardiac troponin I from baseline to 6months and 12months for each patients

  4. Calculate the change of the level of NT-proBNP [ Time Frame: baseline and 6months, 12 months ]
    Calculate the change of the level of NT-proBNP from baseline to 6months and 12months for each patients

  5. Calculate the change of E/A ratio assessed by echocardiography [ Time Frame: baseline and 12 months ]
    Calculate the change of diastolic dysfunction (E/A ratio) assessed by echocardiography from baseline to 12months for each patients

  6. Change of the resting heart rate [ Time Frame: baseline and 6months, 12 months ]
    Calculate the change of the resting heart rate from baseline to 6months and 12months for each patients


Other Outcome Measures:
  1. Number of participants with All cause mortality, cardiac death, or hospitalized due to heart problem [ Time Frame: 12 months ]
    Number of Subjects with All cause mortality, cardiac death, or hospitalized due to heart problem at the end of study

  2. Number of participants with bisoprolol-related adverse events as assessed by the following definition [ Time Frame: 12 months ]
    Bisoprolol treatment-related adverse events including the dizziness, bradyarrhythmia (resting heart rate lower than 55bpm),II and III degree atrioventricular block,hypotension



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   7 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Older than(including) 7 years old
  • A definite diagnosis of DMD with muscle pathology confirming the expression of dystrophin lower than 5% and/or confirmed mutations in the DMD gene using a clinical accepted technique that completely defines the mutation.
  • Using ACEI or ARB for more than 1 month
  • Confirmed myocardial damage in one or more left ventricular segments evident by late gadolinium enhancement and preserved left ventricular systolic function(>45%) by cine cardiac MR in 45 days
  • Normal renal function
  • Holter and blood pressure shows no contraindication of using bisoprolol

Exclusion Criteria:

  • Having metal implanted in body
  • Having claustrophobia
  • Allergic to gadolinium
  • Complicated with other cardiovascular diseases
  • Medical history or Holter show bradyarrhythmia like II/III degree atrioventricular block, sick sinus syndrome etc.
  • Systolic blood pressure lower than 90mmHg or rest heart rate lower than 75bpm
  • Having COPD or asthma history
  • Having other complications: tumor, endocrine diseases
  • Having beta blockers therapy
  • Planned operation in the future 12 months
  • Allergic to bisoprolol

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03779646


Contacts
Layout table for location contacts
Contact: Guo, Doctor +86-010-69155068 xiaoxiaoguopumch@163.com

Locations
Layout table for location information
China, Beijing
Peking Union Medical College Hospital Recruiting
Beijing, Beijing, China
Contact: Xiaoxiao Guo, Dr.         
Sponsors and Collaborators
Peking Union Medical College Hospital
National Natural Science Foundation of China
Chinese Academy of Medical Sciences

Layout table for additonal information
Responsible Party: Xiaoxiao Guo, Associated professor, Peking Union Medical College Hospital
ClinicalTrials.gov Identifier: NCT03779646     History of Changes
Other Study ID Numbers: PekingUMCH-DMD
First Posted: December 18, 2018    Key Record Dates
Last Update Posted: January 21, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Xiaoxiao Guo, Peking Union Medical College Hospital:
Duchenne muscular dystrophy
Early cardiomyopathy
bisoprolol
Additional relevant MeSH terms:
Layout table for MeSH terms
Muscular Dystrophy, Duchenne
Muscular Dystrophies
Cardiomyopathies
Cardiomyopathy, Dilated
Heart Diseases
Cardiovascular Diseases
Muscular Disorders, Atrophic
Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Diseases
Nervous System Diseases
Genetic Diseases, Inborn
Genetic Diseases, X-Linked
Cardiomegaly
Bisoprolol
Antihypertensive Agents
Sympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Adrenergic beta-1 Receptor Antagonists
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action