Bisoprolol in DMD Early Cardiomyopathy

NCT03779646 | Unknown Phase 2

• 1 other identifier: PekingUMCH-DMD
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

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.

Conditions

Duchenne Muscular Dystrophy; Cardiomyopathy, Dilated

Keywords

Duchenne muscular dystrophy; Early cardiomyopathy; bisoprolol

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Calculate the change of left ventricular ejection fraction in cardia MR

  baseline and 12 months

• Calculate the change of ventricle late gadolinium enhancement area in cardia MR

  baseline and 12 months

• Calculate the change of the level of high-sensitivity cardiac troponin I

  baseline and 6months, 12 months

• Calculate the change of the level of NT-proBNP

  baseline and 6months, 12 months

• Calculate the change of E/A ratio assessed by echocardiography

  baseline and 12 months

Other Outcomes (2)

• Number of participants with All cause mortality, cardiac death, or hospitalized due to heart problem

  12 months

• Number of participants with bisoprolol-related adverse events as assessed by the following definition

  12 months

Study Arms (2)

bisoprolol fumarate

EXPERIMENTAL

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

Drug: Bisoprolol Fumarate

Control

NO INTERVENTION

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.

Interventions

Bisoprolol Fumarate 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.

bisoprolol fumarate

Eligibility Criteria

• Age: 7 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Peking Union Medical College Hospital: lead
• National Natural Science Foundation of China: collaborator
• Chinese Academy of Medical Sciences: collaborator

Study Sites (1)

Peking Union Medical College Hospital

Beijing, Beijing Municipality, China

RECRUITING

MeSH Terms

Conditions

Muscular Dystrophy, Duchenne; Cardiomyopathy, Dilated; Cardiomyopathies

Interventions

Bisoprolol

Condition Hierarchy (Ancestors)

Muscular Dystrophies; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Cardiomegaly; Heart Diseases; Cardiovascular Diseases; Laminopathies

Intervention Hierarchy (Ancestors)

Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines

Central Study Contacts

Guo, Doctor

CONTACT

+86-010-69155068; xiaoxiaoguopumch@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associated professor

Model Details: 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.

Study Record Dates

• First Submitted: December 14, 2018
• First Posted: December 19, 2018
• Study Start: January 16, 2019
• Primary Completion: July 1, 2023
• Study Completion: July 1, 2024
• Last Updated: September 28, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)