Bisoprolol in DMD Early Cardiomyopathy

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

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.

Study Overview

• Status: Recruiting
• Conditions: Cardiomyopathy, Dilated; Duchenne Muscular Dystrophy
• Intervention / Treatment: Drug: Bisoprolol Fumarate

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 Type: Interventional
• Enrollment (Anticipated): 42
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Guo, Doctor; Phone Number: +86-010-69155068; Email: xiaoxiaoguopumch@163.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China
      • Recruiting
      • Peking Union Medical College Hospital
      • Contact: Xiaoxiao Guo, Dr.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital
• Collaborators: National Natural Science Foundation of China; Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Study record dates

Study Major Dates

• Study Start (Actual): January 16, 2019
• Primary Completion (Anticipated): July 1, 2023
• Study Completion (Anticipated): July 1, 2024

Study Registration Dates

• First Submitted: December 14, 2018
• First Submitted That Met QC Criteria: December 16, 2018
• First Posted (Actual): December 19, 2018

Study Record Updates

• Last Update Posted (Actual): September 28, 2022
• Last Update Submitted That Met QC Criteria: September 27, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: Duchenne muscular dystrophy; bisoprolol; Early cardiomyopathy
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Muscular Disorders, Atrophic; Cardiomegaly; Laminopathies; Muscular Dystrophies; Cardiomyopathies; Cardiomyopathy, Dilated; Muscular Dystrophy, Duchenne; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Autonomic Agents; Peripheral Nervous System Agents; Sympatholytics; Adrenergic beta-1 Receptor Antagonists; Bisoprolol
• Other Study ID Numbers: PekingUMCH-DMD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No