Clinical trial NCT00606775: The Preventive Efficacy of Carvedilol on Cardiac Dysfunction in Duchenne Muscular Dystrophy
Official title: Carvedilol for the Prevention of Minor Cardiac Damage and Cardiac Function in Duchenne Muscular Dystrophy
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Duchenne Muscular Dystrophy
Cardiomyopathies
Keywords: Adrenergic beta-Antagonists
Duchenne Muscular Dystrophy
Cardiomyopathies
Troponin I
Lead sponsor: Suzuka Hospital
Sponsor class: OTHER_GOV
Collaborators: name: Nagoya University
First posted: 2008-02-05
Enrollment: 60
Sex: MALE
Minimum age (years): 8
Maximum age (years): 45
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Purpose This cardiac dysfunction in patients with Duchenne muscular dystrophy is associated with minor cardiac damage as indicated by elevation of plasma cardiac troponin I (cTnI). The purpose of this study is to investigate whether the administration of Carvedilol can suppress the minor cardiac damage and prevent deterioration of cardiac function.

Detailed description: The life span in patients with Duchenne muscular dystrophy has been extending due to the development of artificial respiratory devices. According to that, the ratio of cardiac dysfunction as a cause of death has been increasing. This cardiac dysfunction was associated with minor cardiac damage as indicated by elevation of plasma cardiac troponin I (cTnI). Furthermore, and the detection rate of cTnI plasma as revealed to be correlated with the deterioration speed of LV dysfunction assessed by serial echocardiography measurements. Accordingly, if this minor cardiac damage is suppressed, it is postulated that the progression of cardiac dysfunction can be stopped. In the cases with ventricular arrhythmia and tachycardia, we found plasma cTnI became undetectable after administration of beta-blocker. Accordingly, we investigate whether administration of beta-blocker, carvedilol can persistently suppress the minor cardiac damage and lead to suppress the deterioration of LV function. Note that his study preventive study for preserved to moderate LV dysfunction and is not intended to the beta-blocker treatment for severe LV dysfunction. Because we assume that the mechanism of elevation of cTnI is different; spontaneous in preserved to mild LV dysfunction in patients but LV wall stress in severe LV dysfunction in patients with Duchenne muscular dystrophy.

Eligibility criteria: Inclusion Criteria:

Male patients with Duchenne muscular dystrophy are required to meet the following criteria:

1. Aged ８ to 45 years
2. Positive plasma cardiac troponin I (0.06ng/mL) at least 4 blood measurement in every 3 month.
3. Left ventricular ejection fraction \>30% by echocardiography assessment
4. Written informed consent

Exclusion Criteria:

Patients with the following conditions will be excluded from the study:

1. Left ventricular ejection fraction \<30%
2. No plasma cTnI elevation
3. beta-blocker is already administered without measurement of plasma cTnI
4. Contraindication against treatment with β blockers
5. Any other serious disease that could potentially complicate the management and follow-up protocols

Primary outcomes:
measure: The suppression of minor cardiac damage indicated as elevation of plasma cTnI
timeFrame: 2 years
Secondary outcomes:
measure: Left ventricular function deterioration assessed by echocardiography In-hospital mortality for cardiac dysfunction In-hospital mortality for any cause Overall mortality
timeFrame: 5 years
Other outcomes:
Locations:
city: Suzuka
country: Japan
facility: Suzuka Hospial
state: Mie
Study officials:
affiliation: Department of Cardiology, Nagoya University Graduate School of Medicine
name: Takao Nishizawa, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sato Y, Yamada T, Taniguchi R, Nagai K, Makiyama T, Okada H, Kataoka K, Ito H, Matsumori A, Sasayama S, Takatsu Y. Persistently increased serum concentrations of cardiac troponin t in patients with idiopathic dilated cardiomyopathy are predictive of adverse outcomes. Circulation. 2001 Jan 23;103(3):369-74. doi: 10.1161/01.cir.103.3.369.
citation: Yasuma F, Konagaya M, Sakai M, Kuru S, Kawamura T. A new lease on life for patients with Duchenne muscular dystrophy in Japan. Am J Med. 2004 Sep 1;117(5):363. doi: 10.1016/j.amjmed.2004.03.028. No abstract available.
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citation: Jefferies JL, Eidem BW, Belmont JW, Craigen WJ, Ware SM, Fernbach SD, Neish SR, Smith EO, Towbin JA. Genetic predictors and remodeling of dilated cardiomyopathy in muscular dystrophy. Circulation. 2005 Nov 1;112(18):2799-804. doi: 10.1161/CIRCULATIONAHA.104.528281. Epub 2005 Oct 24.
citation: Ishikawa Y, Bach JR, Minami R. Cardioprotection for Duchenne's muscular dystrophy. Am Heart J. 1999 May;137(5):895-902. doi: 10.1016/s0002-8703(99)70414-x.