Clinical trial NCT01952028: LAMA2-related Muscular Dystrophy Brain Study
Official title: A LAMA2-related Muscular Dystrophy Study: Brain Magnetic Resonance Imaging (MRI)and Brain Electrophysiology Evaluation
Study type: OBSERVATIONAL
Overall status: WITHDRAWN
Conditions: LAMA2-MD (Merosin Deficient Congenital Muscular Dystrophy, MDC1A)
Keywords: MDC1A
Congenital Muscular Dystrophy
Merosin Deficient
LAMA2
brain white matter abnormalities
Seizure
Lead sponsor: Cure CMD
Sponsor class: OTHER
Collaborators: name: Congenital Muscle Disease International Registr
First posted: 2013-09-27
Enrollment: 0
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: LAMA2-MD

Brief summary: Laminin alpha-2 (LAMA2)-related muscular dystrophy (LAMA2-MD, Merosin Deficient CMD) is a form of congenital muscular dystrophy (CMD). A person with LAMA2-MD will have changes on brain imaging (MRI), a decrease or absence of the protein merosin (laminin 211) on muscle or skin biopsy and changes in the LAMA2 gene that are inherited from both parents. Several studies have described the changes on brain MRI. Brain changes on MRI do not correlate with the partial reduction or absence of merosin on muscle or skin biopsy. 8-30% of people with LAMA2-MD develop seizures. The types of seizures, electroencephalogram changes and common treatment regimens have not been characterized. This study will review the magnetic resonance imaging (MRI) changes, determine whether certain brain MRI changes are linked to seizures and define the common seizure treatment regimens.

Detailed description: LAMA2-MD is a congenital muscular dystrophy (CMD) subtype caused by mutations in the laminin alpha 2 gene. LAMA2-MD may present clinically as an early onset, severe phenotype or a late onset limb girdle phenotype. The early onset form is most commonly associated with a complete absence of merosin on muscle biopsy with profound neonatal hypotonia, possible respiratory distress and feeding difficulties while the late onset form presents with proximal muscle weakness, contractures and is able to achieve walking. In both early and late onset forms, brain white matter abnormalities have been described on brain MRI and approximately 8-30% develop a seizure disorder. On magnetic resonance (MR) spectroscopy, white matter changes are shown to be due to increased water content rather than areas of demyelination. Both, non-ambulant and ambulant patients may develop respiratory insufficiency requiring non-invasive ventilation and scoliosis.

Although several studies have evaluated the correlation between brain MRI white matter changes and cognition, no studies to date have provided a systematic evaluation of brain imaging, electrophysiologic testing and seizures in patients identified by molecular or immunohistochemical testing to have LAMA2-MD.

Eligibility criteria: Inclusion Criteria:

* Genetic confirmation of 2 variants in LAMA2 gene OR muscle biopsy with complete absence of merosin
* Complete authorization to obtain medical records for Congenital Muscle Disease International Registry
* Complete authorization to obtain medical records for National Institutes of Health (NIH)
* Reside in United States or Canada
* Complete registration and intake survey in the Congenital Muscle Disease International Registry

Exclusion Criteria:

- Individuals with LAMA2-MD who have not had a brain MRI

Primary outcomes:
measure: Identify and grade the structural brain abnormalities observed on MRI
timeFrame: up to 5 months
Secondary outcomes:
measure: Seizure History
timeFrame: up to 8 months
measure: Evaluation of baseline and diagnostic electroencephalograms
timeFrame: up to 8 months
measure: Examine the association between brain MRI structural abnormalities and EEG findings
timeFrame: up to 11 months
Other outcomes:
Locations:
city: San Pedro
country: United States
facility: CMDIR
state: California
Study officials:
affiliation: Cure CMD
name: Anne Rutkowski, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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