Deflazacort in Dysferlinopathies - Full Text View

Sponsored by:	Ludwig-Maximilians - University of Munich
Information provided by:	Ludwig-Maximilians - University of Munich
ClinicalTrials.gov Identifier:	NCT00527228

Purpose

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	Intervention	Phase
LGMD2B Miyoshi Myopathy Dysferlinopathy	Drug: deflazacort Drug: placebo	Phase II Phase III

MedlinePlus related topics: Muscle Disorders

Drug Information available for: Deflazacort

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Crossover Assignment, Safety/Efficacy Study
Official Title:	Deflazacort in Dysferlinopathies (LGMD2B/MM) - a Double Blind, Placebo-Controlled Clinical Study

Further study details as provided by Ludwig-Maximilians - University of Munich:

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. [ Time Frame: each 6 months ] [ Designated as safety issue: No ]

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). [ Time Frame: each 6 months ] [ Designated as safety issue: No ]

Enrollment:	25
Study Start Date:	September 2003
Study Completion Date:	September 2008
Primary Completion Date:	April 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
A: Active Comparator 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.
B: Placebo Comparator After 6 months of treatment, and a 3-months wash-out, there is cross-over to Arm A	Drug: placebo

Arms

Assigned Interventions

A: Active Comparator

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.

B: Placebo Comparator

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

Drug: placebo

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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.
Exclusion criteria during the trial are withdrawal of informed consent or lack of compliance.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00527228

Locations

Germany
Friedrich-Baur-Institute, Dept. of Neurology, Ludwig-Maximilians-University of Munich
Munich, Germany, 80801

Sponsors and Collaborators

Ludwig-Maximilians - University of Munich

Investigators

Principal Investigator:

Maggie C. Walter, MD

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

More Information

Additional Information:

Homepage of the German Muscular Dystrophy Network (MD-NET) This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Friedrich-Baur-Institute ( PD Dr. Maggie Walter )
Study ID Numbers:	274/02
Study First Received:	September 6, 2007
Last Updated:	January 27, 2009
ClinicalTrials.gov Identifier:	NCT00527228 History of Changes
Health Authority:	Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Ludwig-Maximilians - University of Munich:

Muscular dystrophy
therapy
steroids
deflazacort

dysferlinopathy
LGMD
MM

Study placed in the following topic categories:

Anti-Inflammatory Agents
Deflazacort
Dysferlinopathy
Immunologic Factors
Immunosuppressive Agents
Muscular Dystrophies
Limb-girdle Muscular Dystrophy Type 2A

Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Diseases
Limb-girdle Muscular Dystrophy, Type 2B
Miyoshi Myopathy
Muscular Dystrophy

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Deflazacort
Muscular Diseases
Immunologic Factors
Neuromuscular Diseases
Musculoskeletal Diseases

Therapeutic Uses
Physiological Effects of Drugs
Nervous System Diseases
Immunosuppressive Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 07, 2009