LGMD2BPhase 2/3NCT00527228
Deflazacort in Dysferlinopathies
A Phase 2/3 study testing deflazacort in people with LGMD2B and Miyoshi Myopathy, run by Ludwig-Maximilians - University of Munich at 1 site in Germany.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- LGMD2B, Miyoshi Myopathy, Dysferlinopathy
- What is being tested?
- deflazacort
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 25 participants
- Where
- 1 siteGermany
- Study dates
- Sep 2003to Sep 2008
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
Germany1 site
Friedrich-Baur-Institute, Dept. of Neurology, Ludwig-Maximilians-University of Munich
Munich, 80801
About this study
Official title: Deflazacort in Dysferlinopathies (LGMD2B/MM) - a Double Blind, Placebo-controlled Clinical Study
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.
Read the 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
- Being tested
- deflazacort, placebo
- Keywords
- Muscular dystrophy, therapy, steroids, deflazacort, dysferlinopathy, LGMD, MM
- Medical subject headings
- Limb-girdle muscular dystrophy, type 2B, Miyoshi myopathy, Dysferlinopathy, Muscular Dystrophies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
deflazacortDrug
Also called Calcort, Corticosteroid
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.
placeboDrug
| Study group | Role | What they receive |
|---|---|---|
| A | Active comparator | After 6 months of treatment, and a 3-months wash-out, there is cross-over to Arm B Receives: Drug: deflazacort |
| B | Placebo comparator | After 6 months of treatment, and a 3-months wash-out, there is cross-over to Arm A Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: each 6 months
Secondary outcomes (1)
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).
Measured: each 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Sep 2007 (estimated)
- Study startSep 2003
- Primary completionApr 2008
- Study completionSep 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for LGMD2BStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ludwig-Maximilians - University of Munich
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Maggie Walter, Ludwig-Maximilians - University of Munich
- Investigators
- Maggie C. Walter, MD, Principal investigator, Friedrich-Baur-Institute, Dept. of Neurology, Ludwig-Maximilians-University of Munich, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00527228
- Sponsor's protocol ID
- 274/02
- Status last verified
- Aug 2015
- First submitted
- 6 Sep 2007
- Last updated
- 2 Sep 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 23406536
Study at a glance
From the registry record, last updated by the sponsor on 2 Sep 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Deflazacort in Dysferlinopathies (LGMD2B/MM) - a Double Blind, Placebo-controlled Clinical Study
- ClinicalTrials.gov ID
- NCT00527228
- Acronym / sponsor ID
- 274/02
- Conditions
- LGMD2B, Miyoshi Myopathy, Dysferlinopathy
- Keywords
- Muscular dystrophy, therapy, steroids, deflazacort, dysferlinopathy, LGMD, MM
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Ludwig-Maximilians - University of MunichUniversity, hospital or other
- Study start
- Sep 2003
- Primary completion
- Apr 2008 (actual)
- Study completion
- Sep 2008 (actual)
- First posted
- 10 Sep 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A | Active comparator | Drug: deflazacortAfter 6 months of treatment, and a 3-months wash-out, there is cross-over to Arm B |
| B | Placebo comparator | Drug: placeboAfter 6 months of treatment, and a 3-months wash-out, there is cross-over to Arm A |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (3 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| deflazacortAlso: Calcort, CorticosteroidIn 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. | Drug | A |
| placebo | Drug | B |
Primary outcome
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
1 secondary outcome
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Sep 2015.
- Derived from this study: PubMed 23406536Walter 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.
- Homepage of the German Muscular Dystrophy Network (MD-NET)Link provided by the sponsor.
Related trials for LGMD2B
RecruitingObservational study
Long-Term Development of Muscular Dystrophy Outcome Assessments
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Enrolling by invitationObservational study
Clinical, Immunological, Morphological and Genetic Characteristics of Patients With Dysferlinopathy (LGMD R2) in the RF
Dysferlinopathy, Miyoshi Myopathy
Enrolling by invitationObservational study
A Multicenter Phenotype-Genotype Analysis of LGMD Patients in China
LGMD, LGMDR2
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Maggie C. Walter, MD principal investigator
Friedrich-Baur-Institute, Dept. of Neurology, Ludwig-Maximilians-University of Munich, Germany
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing deflazacort in people with LGMD2B and Miyoshi Myopathy, run by Ludwig-Maximilians - University of Munich at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Sep 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00527228, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Sep 2015.