Bisoprolol in DMD Early Cardiomyopathy

Sponsor

Peking Union Medical College Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT03779646

Collaborator

National Natural Science Foundation of China (Other), Chinese Academy of Medical Sciences (Other)

Enrollment

Location

Arms

41.5

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

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.

Study Design

Study Type:

Interventional

Anticipated 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.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 :

Jan 16, 2019

Anticipated Primary Completion Date :

May 1, 2021

Anticipated Study Completion Date :

Jul 1, 2022

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

Calculate the change of left ventricle global longitudinal strain in cardiac MR [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

Calculate the change of left ventricular ejection fraction in cardia MR [baseline and 12 months]
Calculate the change of left ventricular ejection fraction in cardia MR from baseline to 12months for each patients
Calculate the change of ventricle late gadolinium enhancement area in cardia MR [baseline and 12 months]
Calculate the change of ventricle late gadolinium enhancement area in cardia MR from baseline to 12months for each patients
Calculate the change of the level of high-sensitivity cardiac troponin I [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
Calculate the change of the level of NT-proBNP [baseline and 6months, 12 months]
Calculate the change of the level of NT-proBNP from baseline to 6months and 12months for each patients
Calculate the change of E/A ratio assessed by echocardiography [baseline and 12 months]
Calculate the change of diastolic dysfunction (E/A ratio) assessed by echocardiography from baseline to 12months for each patients
Change of the resting heart rate [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

Number of participants with All cause mortality, cardiac death, or hospitalized due to heart problem [12 months]
Number of Subjects with All cause mortality, cardiac death, or hospitalized due to heart problem at the end of study
Number of participants with bisoprolol-related adverse events as assessed by the following definition [12 months]
Bisoprolol treatment-related adverse events including the dizziness, bradyarrhythmia (resting heart rate lower than 55bpm)，II and III degree atrioventricular block，hypotension

Eligibility Criteria

Criteria

Ages Eligible for Study:

7 Years and Older

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

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