Duchenne and Becher muscular dystrophy MedDRA version: 9.1 Level: LLT Classification code 10013801 Term: Duchenne muscular dystrophy
Conditions
Interventions
Trade Name: DILATREND
Pharmaceutical Form: Tablet
INN or Proposed INN: Carvedilol
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 6.25-
Trade Name: TRIATEC
Pharmac
Sponsors
POLICLINICO UNIVERSITARIO AGOSTINO GEMELLI
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1) Immunohystochemical and molecular diagnosis of Duchenne and Becker muscular dystrophy. 2) Not evidence of clinical cardiomyopathy, i.e. no cardiac symptoms, normal ECG (see exclusion criteria for details), normal 2D-echocardiography with normal systolic, (left ventricular EF ≥ 55%, right ventricular EF ≥ 45% and absence of regional wall motion abnormalities, WMSI = 1) and diastolic function. 3) DMD patients treated with steroid therapy to modify the overall rate of muscle progression, are eligible to enter the study. 4) All DMD and BMD patients enrolled in this study are not treated with cardiological therapy (ACE-inhibitors, ARBs or Beta-Blockers). 5) Written informed consent to study participation (with serial visit, CMR and echocardiographic study) is required from all patients themselves, as well as their parent or guardian and healthy-control subjects. Are the trial subjects under 18? yes Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1) Failure to obtain informed consent from patients, parents or guardians. 2) Any controindications to carvedilol or ramipril treatment. In particular all patients with bronchial asthma, diabetes, any degree of renal failure (all patients are required to have a normal creatinine level and clearance) . 3) DMD patients will be excluded if present ECGs anomalies as follows: tall R waves in the right precordial leads, with an abnormal R/S ratio, a deep and narrow Q wave greater than 4 mm over leads I, V5 and V6. in BMD patients ECG changes suggestive of ischemic heart disease, left bundle-branch block, atrial flutter/fibrillation, ventricular arrhythmias, any degree of atrioventricular block and left ventricular (LV) hypertrophy. Aspecific ST changes will be not considered as electrocardiographic exclusion criteria both in DMD and BMD patients. 4) In BMD patients exclusion criteria will be also hypertension and valvular heart disease other than trivial. 5) DMD and BMD patients requiring ventilatory (non-invasive or invasive) assistance. 6) Presence of systolic and/or diastolic dysfunction detected by 2D-Echocardiography. 7) Presence of any contraindications to CMR (including any history of claustrophobia). 8) Patients under the age of 2 years. 9) Renal failure, even mild. 10) Patient unable or unwilling to attend the follow-up and tests, in the opinion of local study principal investigator, (children not willing to perform CMR will not be enrolled).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: ) to compare the efficacy of therapy with carvedilol vs ramipril on evolution of cardiac involvement in Duchenne (DMD) and Becker (BMD) individuals, with normal baseline cardiac function 2) to define the clinical significance and prognostic value of late gadolinium enhancement (LGE).;Secondary Objective: 2. To investigate if, early presence of myocardial LGE in DMD and BMD patients without cardiomyopathy, might be an early marker of cardiac involvement (used as outcome measure) and the LGE prognostic implications, since patients with myocardial fibrosis may have a significantly worse prognosis and adverse outcomes, respect to patients without myocardial LGE. 3. To assess the relationships between cardioprotective therapy, myocardial LGE, evolution and development of cardiomyopathy in a long-term follow-up. CMR might identify a subset of patients (Becker patients) at higher risk, in whom cardioprotective therapy might be most effective or patients needing different therapy (carvedilol more effective vs. ramipril) or viceversa.;Primary end point(s): To compare left ventricular Ejection Fraction, systolic and diastolic left ventricular volumes, LGE (as a quantitative dimension) and UTC values in patients treated with carvedilol vs ramipril. | — |
Countries
Italy
Outcome results
None listed