Deflazacort in Dysferlinopathies

NCT ID: NCT00527228

Last Updated: 2015-09-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-09-30
• Study Completion Date: 2008-09-30

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.

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.

Conditions

LGMD2B; Miyoshi Myopathy; Dysferlinopathy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

A

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

Group Type: ACTIVE_COMPARATOR

deflazacort

Intervention Type: DRUG

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.

B

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

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

Interventions

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.

Intervention Type: DRUG

placebo

Intervention Type: DRUG

Other Intervention Names

Calcort; Corticosteroid

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ludwig-Maximilians - University of Munich

OTHER

Sponsor Role: lead

Responsible Party

Maggie Walter

Prof. Dr. Maggie C. Walter, MD, MA

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Maggie C. Walter, MD

Role: PRINCIPAL_INVESTIGATOR

Friedrich-Baur-Institute, Dept. of Neurology, Ludwig-Maximilians-University of Munich, Germany

Locations

Friedrich-Baur-Institute, Dept. of Neurology, Ludwig-Maximilians-University of Munich

Munich, , Germany

Countries

Germany

References

Walter MC, Reilich P, Thiele S, Schessl J, Schreiber H, Reiners K, Kress W, Muller-Reible C, Vorgerd M, Urban P, Schrank B, Deschauer M, Schlotter-Weigel B, Kohnen R, Lochmuller H. Treatment of dysferlinopathy with deflazacort: a double-blind, placebo-controlled clinical trial. Orphanet J Rare Dis. 2013 Feb 14;8:26. doi: 10.1186/1750-1172-8-26.

Reference Type: DERIVED

PMID: 23406536 (View on PubMed)

Related Links

http://www.md-net.org

Homepage of the German Muscular Dystrophy Network (MD-NET)

Other Identifiers

274/02

Identifier Type: -

Identifier Source: org_study_id