Clinical trial NCT03779646: Bisoprolol in DMD Early Cardiomyopathy
Official title: Bisoprolol for Early Cardiomyopathy in Duchenne Muscular Dystrophy: a Randomized, Controlled Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Duchenne Muscular Dystrophy
Cardiomyopathy, Dilated
Keywords: Duchenne muscular dystrophy
Early cardiomyopathy
bisoprolol
Lead sponsor: Peking Union Medical College Hospital
Sponsor class: OTHER
Collaborators: name: National Natural Science Foundation of China
name: Chinese Academy of Medical Sciences
First posted: 2018-12-19
Enrollment: 42
Sex: MALE
Minimum age (years): 7
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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

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.

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.

Eligibility 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

Primary outcomes:
measure: Calculate the change of left ventricle global longitudinal strain in cardiac MR
timeFrame: baseline and 12 months
Secondary outcomes:
measure: Calculate the change of left ventricular ejection fraction in cardia MR
timeFrame: baseline and 12 months
measure: Calculate the change of ventricle late gadolinium enhancement area in cardia MR
timeFrame: baseline and 12 months
measure: Calculate the change of the level of high-sensitivity cardiac troponin I
timeFrame: baseline and 6months, 12 months
measure: Calculate the change of the level of NT-proBNP
timeFrame: baseline and 6months, 12 months
measure: Calculate the change of E/A ratio assessed by echocardiography
timeFrame: baseline and 12 months
measure: Change of the resting heart rate
timeFrame: baseline and 6months, 12 months
Other outcomes:
measure: Number of participants with All cause mortality, cardiac death, or hospitalized due to heart problem
timeFrame: 12 months
measure: Number of participants with bisoprolol-related adverse events as assessed by the following definition
timeFrame: 12 months
Locations:
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
Study officials:
References: