LAMA2-related Muscular Dystrophy Brain Study

March 5, 2018 updated by: Cure CMD

A LAMA2-related Muscular Dystrophy Study: Brain Magnetic Resonance Imaging (MRI)and Brain Electrophysiology Evaluation

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.

Study Overview

Status

Withdrawn

Conditions

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.

Study Type

Observational

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • San Pedro, California, United States, 90732
        • CMDIR

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

LAMA2-MD

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Cross-Sectional

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Identify and grade the structural brain abnormalities observed on MRI
Time Frame: up to 5 months
Both single and longitudinal brain MRIs will be retrieved with patient consent from hospitals within the United States. Two trained neuroradiologists will evaluate de-identified brain MRIs using a pre-determined scoring system to identify and classify structural abnormalities.
up to 5 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Seizure History
Time Frame: up to 8 months
To obtain a seizure history on all individuals with LAMA2-MD who have had a seizure, including: type of seizures, age of seizure onset, seizure frequency, need for mechanical ventilation, seizure medications, and need for emergency room (ER) visit or hospitalization.
up to 8 months
Evaluation of baseline and diagnostic electroencephalograms
Time Frame: up to 8 months
Both baseline and diagnostic electroencephalograms (EEG) will be obtained with patient consent from hospitals within the United States. An epileptologist will review de-identified EEG recordings to identify and classify abnormalities using a predetermined scoring system.
up to 8 months
Examine the association between brain MRI structural abnormalities and EEG findings
Time Frame: up to 11 months
Compare the frequency of various grades of brain MRI abnormalities in individuals with LAMA2-MD with and without seizures. Identify any association between MRI abnormality and type of seizure.
up to 11 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Cure CMD

Collaborators

Congenital Muscle Disease International Registr

Investigators

  • Principal Investigator: Anne Rutkowski, MD, PhD, Cure CMD

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2013

Primary Completion (Anticipated)

November 1, 2014

Study Completion (Anticipated)

December 1, 2014

Study Registration Dates

First Submitted

September 19, 2013

First Submitted That Met QC Criteria

September 24, 2013

First Posted (Estimate)

September 27, 2013

Study Record Updates

Last Update Posted (Actual)

March 7, 2018

Last Update Submitted That Met QC Criteria

March 5, 2018

Last Verified

October 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CMDIR-003

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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