Bisoprolol in DMD Early Cardiomyopathy

NCT ID: NCT03779646

Last Updated: 2022-09-28

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 42 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-01-16
• Study Completion Date: 2024-07-01

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.

Conditions

Duchenne Muscular Dystrophy; Cardiomyopathy, Dilated

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

bisoprolol fumarate

In this arm, the participants will receive different dose of bisoprolol fumarate.

Group Type: EXPERIMENTAL

Bisoprolol Fumarate

Intervention Type: DRUG

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.

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.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

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.

Intervention Type: DRUG

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

• Minimum Eligible Age: 7 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

National Natural Science Foundation of China

OTHER_GOV

Sponsor Role: collaborator

Chinese Academy of Medical Sciences

OTHER

Sponsor Role: collaborator

Peking Union Medical College Hospital

OTHER

Sponsor Role: lead

Responsible Party

Xiaoxiao Guo

Associated professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Peking Union Medical College Hospital

Beijing, Beijing Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Guo, Doctor

Role: CONTACT

xiaoxiaoguopumch@163.com

+86-010-69155068

Facility Contacts

Xiaoxiao Guo, Dr.

Role: primary

Other Identifiers

PekingUMCH-DMD

Identifier Type: -

Identifier Source: org_study_id