The Preventive Efficacy of Carvedilol on Cardiac Dysfunction in Duchenne Muscular Dystrophy

Duchenne Muscular Dystrophy Clinical Trial

Official title:

Carvedilol for the Prevention of Minor Cardiac Damage and Cardiac Function in Duchenne Muscular Dystrophy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00606775
• Other study ID #: TN1966220
• Status: Recruiting
• Phase: Phase 4
• First received: January 22, 2008
• Last updated: February 4, 2008
• Start date: December 2007
• Est. completion date: December 2012

Study information

• Verified date: December 2007
• Source: Suzuka Hospital
• Contact: Takao Nishizawa, MD,PhD
• Phone: +81-52-744-2150
• Email: nishizta[@]med.nagoya-u.ac.jp
• Is FDA regulated: No
• Health authority: Japan: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: December 2012
• Est. primary completion date: December 2008
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 8 Years to 45 Years

Eligibility

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 ß blockers

5. Any other serious disease that could potentially complicate the management and follow-up protocols

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Cardiomyopathies
• Duchenne Muscular Dystrophy
• Muscular Dystrophies
• Muscular Dystrophy, Duchenne

Intervention

Drug:
• Carvedilol
2.5-5mg/day

Locations

Country	Name	City	State
Japan	Suzuka Hospial	Suzuka	Mie

Sponsors (2)

Lead Sponsor	Collaborator
Suzuka Hospital	Nagoya University

Country where clinical trial is conducted

Japan, 

References & Publications (5)

Hunsaker RH, Fulkerson PK, Barry FJ, Lewis RP, Leier CV, Unverferth DV. Cardiac function in Duchenne's muscular dystrophy. Results of 10-year follow-up study and noninvasive tests. Am J Med. 1982 Aug;73(2):235-8. — View Citation

Ishikawa Y, Bach JR, Minami R. Cardioprotection for Duchenne's muscular dystrophy. Am Heart J. 1999 May;137(5):895-902. — View 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. Epub 2005 Oct 24. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The suppression of minor cardiac damage indicated as elevation of plasma cTnI		2 years	Yes
Secondary	Left ventricular function deterioration assessed by echocardiography In-hospital mortality for cardiac dysfunction In-hospital mortality for any cause Overall mortality		5 years	No