Evaluation of Limb-Girdle Muscular Dystrophy

Study Overview
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Brief Summary
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The purpose of this study is to understand the biochemistry of different types of Limb-Girdle Muscular Dystrophy (LGMD) and to determine appropriate outcome measures for future clinical treatment trials for LGMD. It is being conducted at two sites in the Cooperative International Neuromuscular Research Group (CINRG). It involves a one day clinical evaluation at a participating institution that will take approximately four to six hours, and will involve strength testing and muscle functional testing by a physical therapist, an evaluation by a physician, pulmonary function testing, a complete cardiac evaluation with electrocardiogram (ECG or EKG) and echocardiogram (Echo), and involve two blood draws, one before the evaluation and one after the evaluation is complete. During the visit, the participant will be asked to fill out a couple of questionnaires asking questions about quality of life and activity limitations, as well as his/her understanding of their diagnosis with regards to etiology (or cause of their muscle disorder), genetics, and inheritance of their muscle disorder.

Detailed Description
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Specific Aims: Aim 1: Evaluate integrity of the extracellular matrix in patients with LGMD by measuring serum growth factors and cytokines and compare these to a disease control (BMD) and normal volunteers. Aim 2: Measure growth factors and cytokines following medical evaluation and compare them to the baseline levels. Aim 3: Discovery Aim for future multicenter clinical trials in LGMD. Aim 3A: Abstract medical records with particular emphasis on age of disease onset, initial clinical symptoms, progression and location of the muscular weakness, treatments attempted, and other medical complications. A review of the diagnostic testing performed will also be conducted. Aim 3B: Perform complete clinical evaluation including anthropometric measures, evaluation of joint limitations, timed functional testing, muscle strength, pulmonary function, and a cardiac assessment. Aim 3C: Determine patient understanding of diagnosis of LGMD and genetic testing results. A questionnaire will be generated that addresses the patient's understanding of his/her diagnosis as well as their understanding of genetic concepts of autosomal recessive inheritance, genes, molecular testing and implications for themselves as well as their family. Aim 3D: Quality of Life (QOL) questionnaires will be administered. These will be used to identify functional limitations by the patients and compare those limitations with the clinical evaluation. Study Description Only one visit will be necessary for this study. The study visit includes: Review of the informed consent form Blood collection Blood will be collected for the following: DNA extraction to confirm genotype if not already performed; Muscle Enzymes before and after physical evaluation; and Growth factors and cytokines: before and after physical evaluation. Medical history review Physical Examination Questionnaires: Participants will complete 3 questionnaires: Diagnosis and genetic testing, ACTIVLIM, and INQoL Clinical Evaluator assessment which includes: Manual Muscle Testing, Quantitative Muscle Testing, Pulmonary Function Testing, Anthropometric measurements, and Timed and Functional testing Cardiac evaluation will include: Electrocardiogram and Echocardiogram Control subjects will be required to come to the test site to complete the informed consent process, clinical evaluator assessment, and have blood drawn before and after the clinical evaluator assessment. No other examinations or procedures will be performed on the control participants.

Official Title
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Evaluation of Limb-Girdle Muscular Dystrophy

Conditions
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Becker Muscular Dystrophy, Limb-Girdle Muscular Dystrophy, Type 2A (Calpain-3 Deficiency), Limb-Girdle Muscular Dystrophy, Type 2B (Miyoshi Myopathy, Dysferlin Deficiency), Limb-Girdle Muscular Dystrophy, Type 2I (FKRP-deficiency)

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years of age or older. Diagnosis of LGMD2I, LGMD2A, LGMD2B, or BMD as determined by muscle biopsy immunohistochemistry, immunoblotting, or molecular analysis. Able to travel to study site Normal controls will be recruited as either friends of the study participants or through separate recruitment. Exclusion Criteria: Unable to travel to study site. Do not have the diagnosis of LGMD2I, LGMD2A, LGMD2B, or BMD after review of clinical testing.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| BMD:<br>Patients diagnosed with Becker Muscular Dystrophy | |
| LGMD2A<br>patient diagnosed with Limb-Girdle Muscular Dystrophy, type 2A Calpain-3 deficiency | |
| LGMD2B<br>Patients diagnosed with Limb-Girdle Muscular Dystrophy, type 2B Miyoshi myopathy Dysferlin deficiency | |
| LGMD2I<br>Patients diagnosed with Limb-Girdle Muscular Dystrophy, type 2I FKRP-deficiency | |
| Control<br>Healthy Controls | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The measurement of growth factors (TGF-B, IGF-II) and cytokines (IL18, IL1A, and IL1B) between the different types of LGMD and BMD. |  | 12 months | 
| The difference in the growth factors (TGF-B, IGF-II) and cytokines (IL18, IL1A, and IL1B) pre-evaluation and post-evaluation. |  | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of surrogate and clinically relevant outcome measures in LGMD. |  | 24 months | 
| Quality of life questionnaires to correlate patient- perceived limitations in daily activities with the quantitative strength measurements and functional ability with timed testing. |  | 24 months | 
| Evaluation of patient understanding in their diagnosis and genetic etiology of their diagnosis. |  | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Duchenne and Becker muscular dystrophy, muscular dystrophy