Deflazacort in Dysferlinopathies

Ludwig Maximilian University of Munich

Status and phase

Completed

Phase 3

Phase 2

Conditions

LGMD2B

Dysferlinopathy

Miyoshi Myopathy

Treatments

Drug: placebo

Drug: deflazacort

Study type

Interventional

Funder types

Other

Identifiers

NCT00527228

274/02

Details and patient eligibility

About

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.

Full 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.

Enrollment

25 patients

Sex

All

Ages

18+ years old

Volunteers

No 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.