Deflazacort in Dysferlinopathies

Sponsor

Ludwig-Maximilians - University of Munich (Other)

Overall Status

Completed

CT.gov ID

NCT00527228

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The present study is designed to assess the natural history in a one year pre-phase of the trial and evaluate therapeutic efficacy and side effects of deflazacort in LGMD2B/MM patients in a placebo-controlled trial. Furthermore, long-term development of the disease under naturalistic conditions will be documented in a 2-year follow-up after the end of the double-blind treatment phase.

Condition or Disease	Intervention/Treatment	Phase
LGMD2B Miyoshi Myopathy Dysferlinopathy	Drug: deflazacort Drug: placebo	Phase 2/Phase 3

Detailed Description

Limb girdle muscular dystrophies (LGMDs) are a genetically heterogeneous group of disorders encompassing various genetically defined subtypes (LGMD 2A-2H). Therapeutic trials should address each disease entity separately to assess effectiveness of medical treatments. A placebo-controlled trial in patients with dysferlinopathy may reveal insights in the natural course of the disease and show therapeutic options in a homogeneous group of patients. So far, steroids are the only drugs showing efficacy in muscular dystrophies, mainly in Duchenne muscular dystrophy (DMD). Both dystrophin and dysferlin are attached to the sarcolemma and deficiency of both proteins cause sarcolemmal defects; therefore, any membrane-stabilizing steroid effect may be beneficial in both DMD and LGMD2B/ Myoshi myopathy (MM). Furthermore, there is marked inflammation in muscle biopsies of many LGMD2B patients. Therefore, the anti-inflammatory effect of steroids may improve muscle function in LGMD2B/MM. In our trial, effects of deflazacort in patients with dysferlinopathy (LGMD2B/MM) on strength and daily-life activities are addressed. The present study is designed to assess the natural history and evaluate therapeutic efficacy and side effects of deflazacort / placebo in LGMD2B/MM patients.

Although no major therapeutic breakthrough has been achieved and curative treatment modalities are not yet applicable, life expectancy and quality of life of dysferlinopathy patients could be remarkably improved by establishing a drug therapy, capable of delaying the dystrophic process and improving muscle strength and function. Therefore, the results of this study are warranted and may influence further guidelines for steroid treatment in dysferlinopathies. Furthermore, the assessment of the natural history of the disease will provide new insights in the clinical understanding of dysferlinopathies.

Study Design

Study Type:

Interventional

Actual Enrollment :

25 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Deflazacort in Dysferlinopathies (LGMD2B/MM) - a Double Blind, Placebo-controlled Clinical Study

Study Start Date :

Sep 1, 2003

Actual Primary Completion Date :

Apr 1, 2008

Actual Study Completion Date :

Sep 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: A After 6 months of treatment, and a 3-months wash-out, there is cross-over to Arm B	Drug: deflazacort In the first 12 months, patients will receive no treatment to assess the natural history of the disease. Afterwards, patients will be treated with deflazacort 1mg/kg/day or placebo for the first month on treatment, from the second month on deflazacort or placebo will be administered on an alternate day regimen). Patients will be randomized to six months verum or placebo each, after a 3-months wash-out patients cross over to the alternate treatment for six months. In a 2-years follow-up phase after the double-blind treatment phase, long-term development of the disorder will be documented. Other Names: Calcort Corticosteroid
Placebo Comparator: B After 6 months of treatment, and a 3-months wash-out, there is cross-over to Arm A	Drug: placebo

Arm

Intervention/Treatment

Active Comparator: A

After 6 months of treatment, and a 3-months wash-out, there is cross-over to Arm B

Drug: deflazacort

In the first 12 months, patients will receive no treatment to assess the natural history of the disease. Afterwards, patients will be treated with deflazacort 1mg/kg/day or placebo for the first month on treatment, from the second month on deflazacort or placebo will be administered on an alternate day regimen). Patients will be randomized to six months verum or placebo each, after a 3-months wash-out patients cross over to the alternate treatment for six months. In a 2-years follow-up phase after the double-blind treatment phase, long-term development of the disorder will be documented.

Other Names:

Calcort

Corticosteroid

Placebo Comparator: B

After 6 months of treatment, and a 3-months wash-out, there is cross-over to Arm A

Drug: placebo

Outcome Measures

Primary Outcome Measures

Muscle strength according to Medical Research Council Scales (MRC) and quantitative strength measurement evaluated by hand-held dynamometry (Citec, Groningen, The Netherlands)in the same muscle groups. [each 6 months]

Secondary Outcome Measures

Quantitative strength measurement (QSM, M3diagnos, Fa. Schnell, Germany), Neuromuscular Symptoms Score (NSS), timed function tests, Clinical Global Impressions (CGI) of change and quality of life assessment(SF-36 scale). [each 6 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Clinically, histologically, immunohistochemically and genetically defined muscular dystrophy with dysferlin-deficiency (LGMD2B/MM).
Patients should fulfill clinical, morphological, immunohistochemical and immunoblot criteria of LGMD 2B and definite mutation in dysferlin gene.
There is no limitation on age for study inclusion.

Exclusion Criteria:

Patients confined to bed or wheelchair.
Patients with other neurologic or internistic diseases and patients with former or current steroid treatment will not be included.
Exclusion criteria during the trial are withdrawal of informed consent or lack of compliance.