Nebivolol for the Prevention of Left Ventricular Systolic Dysfunction in Patients With Duchenne Muscular Dystrophy

Study Overview
=================
Brief Summary
-----------------
The objective is to determine whether nebivolol, a beta-blockade drug, can prevent the development of heart disease in patients with Duchenne muscular dystrophy aged 10 to 15 year-old.

Detailed Description
-----------------
A 1.25 mg-test dose will be administrated to assess the treatment tolerance before randomization. A forced titration of nebivolol and placebo will be performed with 2 weeks periods. Full dose of nebivolol and placebo is 5mg/day (7.5mg/day for patients whose weight is>60kg).

Official Title
-----------------
A Randomized, Double-Blind, Placebo-Controlled, Multi-center Study to Examine the Effect of Nebivolol, a Beta-Blockade Drug, for the Prevention of Ventricular Systolic Dysfunction in Patients With Duchenne Muscular Dystrophy

Conditions
-----------------
Duchenne Muscular Dystrophy, Cardiomyopathy, Heart Failure

Intervention / Treatment
-----------------
* Drug: Nebivolol
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Duchenne muscular dystrophy genetically proven Age between 10 and 15 years Left ventricular ejection fraction assessed by radionuclide angiography or echocardiography ≥50% and measured within 3 months Systolic blood pressure ≥80 mmHg Diastolic blood pressure ≥70 mmHg Exclusion Criteria: Heart rate <50 bpm 2nd or 3rd degree atrioventricular blocks, sinus node dysfunction Asthma or bronchospasm Severe peripheral circulatory disease Hypersensitivity to nebivolol or excipients Metabolic acidosis Blood urea >7 mmol/l Liver transaminases enzymes >6 fold the upper limit of normal Formal indication for beta-blockade treatment Cardiac treatments except angiotensin-converting enzyme inhibitors Participation to another clinical trial within 3 months

Ages Eligible for Study
-----------------
Minimum Age: 10 Years
Maximum Age: 15 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nebivolol<br> | Drug: Nebivolol<br>* A 1.25mg-test dose will be administrated to assess the treatment tolerance before randomization. A forced titration of nebivolol will be performed with 2 weeks periods. Full dose of nebivolol is 5mg/day (7.5mg/day for patients whose weight is>60kg)<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* A 1.25mg-test dose of nebivolol will be administrated to assess the treatment tolerance before randomization. A forced titration of placebo will be performed with 2 weeks periods. Full dose of placebo is 5mg/day (7.5mg/day for patients whose weight is>60kg)<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Left ventricular systolic dysfunction | Development of left ventricular systolic dysfunction with an ejection fraction < 45% | at 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Right ventricular ejection fraction | Right ventricular ejection fraction assessed by radionuclide angiography or echocardiography | at 5 years | 
| NT-ProBNP | NT-ProBNP | at 1, 2, 3, 4, and 5 years | 
| Left ventricular dysfunction | Development of left ventricular dysfunction | at 10 years | 
| Hospitalizations | hospitalizations for heart failure | at 10 years | 
| Mortality | Cardiovascular mortality | at 10 years ((5-years open label extension) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Nebivolol, beta-blockade treatment