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Bisoprolol in DMD Early Cardiomyopathy

Primary Purpose

Duchenne Muscular Dystrophy, Cardiomyopathy, Dilated

Status

Recruiting

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

Bisoprolol Fumarate

About this trial

This is an interventional treatment trial for Duchenne Muscular Dystrophy focused on measuring Duchenne muscular dystrophy, Early cardiomyopathy, bisoprolol

Eligibility Criteria

7 Years - undefined (Child, Adult, Older Adult)MaleDoes not accept 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

Sites / Locations

Peking Union Medical College HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

bisoprolol fumarate

Control

Arm Description

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

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

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

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

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

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

Change of the resting heart rate

Calculate the change of the resting heart rate from baseline to 6months and 12months for each patients

Full Information

NCT ID

NCT03779646

First Posted

December 14, 2018

Last Updated

September 27, 2022

Sponsor

Peking Union Medical College Hospital

Collaborators

National Natural Science Foundation of China, Chinese Academy of Medical Sciences

1. Study Identification

Unique Protocol Identification Number

NCT03779646

Brief Title

Bisoprolol in DMD Early Cardiomyopathy

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2022

Overall Recruitment Status

Recruiting

Study Start Date

January 16, 2019 (Actual)

Primary Completion Date

July 1, 2023 (Anticipated)

Study Completion Date

July 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Peking Union Medical College Hospital

Collaborators

National Natural Science Foundation of China, Chinese Academy of Medical Sciences

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Duchenne Muscular Dystrophy, Cardiomyopathy, Dilated

Keywords

Duchenne muscular dystrophy, Early cardiomyopathy, bisoprolol

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Parallel Assignment

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.

Masking

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.

Allocation

Randomized

Enrollment

42 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

bisoprolol fumarate

Arm Type

Experimental

Arm Description

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

Arm Title

Control

Arm Type

No Intervention

Arm Description

Intervention Type

Drug

Intervention Name(s)

Bisoprolol Fumarate

Intervention Description

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.

Primary Outcome Measure Information:

Title

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

Description

Calculate the change of left ventricle global longitudinal strain in cardiac MR from baseline to 12months for each patients

Time Frame

baseline and 12 months

Secondary Outcome Measure Information:

Title

Calculate the change of left ventricular ejection fraction in cardia MR

Description

Calculate the change of left ventricular ejection fraction in cardia MR from baseline to 12months for each patients

Time Frame

baseline and 12 months

Title

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

Description

Calculate the change of ventricle late gadolinium enhancement area in cardia MR from baseline to 12months for each patients

Time Frame

baseline and 12 months

Title

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

Description

Calculate the change of the level of high-sensitivity cardiac troponin I from baseline to 6months and 12months for each patients

Time Frame

baseline and 6months, 12 months

Title

Calculate the change of the level of NT-proBNP

Description

Calculate the change of the level of NT-proBNP from baseline to 6months and 12months for each patients

Time Frame

baseline and 6months, 12 months

Title

Calculate the change of E/A ratio assessed by echocardiography

Description

Calculate the change of diastolic dysfunction (E/A ratio) assessed by echocardiography from baseline to 12months for each patients

Time Frame

baseline and 12 months

Title

Change of the resting heart rate

Description

Calculate the change of the resting heart rate from baseline to 6months and 12months for each patients

Time Frame

baseline and 6months, 12 months

Other Pre-specified Outcome Measures:

Title

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

Description

Number of Subjects with All cause mortality, cardiac death, or hospitalized due to heart problem at the end of study

Time Frame

12 months

Title

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

Description

Bisoprolol treatment-related adverse events including the dizziness, bradyarrhythmia (resting heart rate lower than 55bpm)，II and III degree atrioventricular block，hypotension

Time Frame

12 months

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

7 Years

Accepts Healthy Volunteers

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Guo, Doctor

Phone

+86-010-69155068

xiaoxiaoguopumch@163.com

Facility Information:

Facility Name

Peking Union Medical College Hospital

City

Beijing

State/Province

Beijing

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Xiaoxiao Guo, Dr.

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Bisoprolol in DMD Early Cardiomyopathy

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