Bisoprolol in DMD Early Cardiomyopathy

Duchenne Muscular Dystrophy Clinical Trial

Official title:

Bisoprolol for Early Cardiomyopathy in Duchenne Muscular Dystrophy: a Randomized, Controlled Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03779646
• Other study ID #: PekingUMCH-DMD
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: January 16, 2019
• Est. completion date: July 1, 2024

Study information

• Verified date: September 2022
• Source: Peking Union Medical College Hospital
• Contact: Guo, Doctor
• Phone: +86-010-69155068
• Email: xiaoxiaoguopumch[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 42
• Est. completion date: July 1, 2024
• Est. primary completion date: July 1, 2023
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 7 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cardiomyopathies
• Cardiomyopathy, Dilated
• Duchenne Muscular Dystrophy
• Muscular Dystrophies
• Muscular Dystrophy, Duchenne

Intervention

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.

Locations

Country	Name	City	State
China	Peking Union Medical College Hospital	Beijing	Beijing

Sponsors (3)

Lead Sponsor	Collaborator
Peking Union Medical College Hospital	Chinese Academy of Medical Sciences, National Natural Science Foundation of China

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of participants with All cause mortality, cardiac death, or hospitalized due to heart problem	Number of Subjects with All cause mortality, cardiac death, or hospitalized due to heart problem at the end of study	12 months
Other	Number of participants with bisoprolol-related adverse events as assessed by the following definition	Bisoprolol treatment-related adverse events including the dizziness, bradyarrhythmia (resting heart rate lower than 55bpm),II and III degree atrioventricular block,hypotension	12 months
Primary	Calculate the change of left ventricle global longitudinal strain in cardiac MR	Calculate the change of left ventricle global longitudinal strain in cardiac MR from baseline to 12months for each patients	baseline and 12 months
Secondary	Calculate the change of left ventricular ejection fraction in cardia MR	Calculate the change of left ventricular ejection fraction in cardia MR from baseline to 12months for each patients	baseline and 12 months
Secondary	Calculate the change of ventricle late gadolinium enhancement area in cardia MR	Calculate the change of ventricle late gadolinium enhancement area in cardia MR from baseline to 12months for each patients	baseline and 12 months
Secondary	Calculate the change of the level of high-sensitivity cardiac troponin I	Calculate the change of the level of high-sensitivity cardiac troponin I from baseline to 6months and 12months for each patients	baseline and 6months, 12 months
Secondary	Calculate the change of the level of NT-proBNP	Calculate the change of the level of NT-proBNP from baseline to 6months and 12months for each patients	baseline and 6months, 12 months
Secondary	Calculate the change of E/A ratio assessed by echocardiography	Calculate the change of diastolic dysfunction (E/A ratio) assessed by echocardiography from baseline to 12months for each patients	baseline and 12 months
Secondary	Change of the resting heart rate	Calculate the change of the resting heart rate from baseline to 6months and 12months for each patients	baseline and 6months, 12 months