Skeletal Muscle Biomarkers in People With Fragile Sarcolemmal Muscular Dystrophy

Study Description

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Brief Summary:

Background:

- Some kinds of muscular dystrophy affect the skeletal muscle membrane. In these conditions, the muscle membrane is more fragile. This affects how the muscles contract and relax, which causes movement problems. Researchers are looking at several muscle enzymes, or chemicals that affect how muscle cells function. By studying changes in these enzymes, they may be able to better understand how muscular dystrophy affects the cells. Researchers want to collect biomarkers (chemicals from blood samples) from people with fragile sarcolemmal muscular dystrophy. This information may provide better treatments for this condition.

Objectives:

- To study biomarkers that may affect the muscles of people with fragile sarcolemmal muscular dystrophy.

Eligibility:

- Individuals at least 18 years of age with fragile sarcolemmal muscular dystrophy.

Design:

• Participants will be screened with a medical history and physical exam.
• Participants will be asked to come for four visits to the National Institutes of Health Clinical Center. The visits will be at least 2 months apart. Each visit will require participants to stay for 5 days at the clinical center.
• During each visit, participants will provide frequent small blood samples. These samples will be collected while at rest and after physical exercise.
• Participants will also have a physical therapy assessment. They will perform standard motor function tests and imaging tests (MRI, MRS). These tests may take up to 1 hour each time.
• Treatment will not be provided as part of this study.

Condition or disease
Genetic Disorder

Detailed Description:

Objectives: the aim of this protocol is to identify biomarker and clinical correlates of changes in the barrier function of skeletal muscle membrane (i.e. cell membrane permeability) before and after routine motor function testing in patients with one of the Fragile Sarcolemmal Muscular Dystrophies (FSMD).

Study population: patients with early adulthood or later onset of a FSMD (LGMD2B-F, I, L, MM, BMD, and MMD3).

Design: pilot study.

Outcome measures: increased change in baseline levels of proteins that are released into the blood from damaged skeletal muscle, such as creatine kinase (CK), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), alanine aminotransferase (ALT), troponins, and myoglobin in serum, changes in inflammation markers, circulating microRNAs and imaging studies to identify effective biomarkers for use in future clinical trials.

Study Design

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Study Type :	Observational
Actual Enrollment :	11 participants
Time Perspective:	Prospective
Official Title:	Pilot Study to Assess Biomarkers of Changes in Barrier Function of Skeletal Muscle in Patients With a Fragile Sarcolemmal Muscular Dystrophy
Study Start Date :	May 9, 2013
Estimated Primary Completion Date :	February 20, 2021
Estimated Study Completion Date :	February 20, 2021

Groups and Cohorts

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Outcome Measures

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :

1. changes in serum enzyme, protein, cytokine and microRNA levels with both activity and time [ Time Frame: multiple assessments within each visit for 4 visits total over 3 years ]
2. changes in motor function abilities [ Time Frame: once each visit ]

Eligibility Criteria

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

• INCLUSION CRITERIA:
• Aged 18 or older
• Have a confirmed genetic diagnosis of one of the FSMDs or have a clinical phenotype consistent with one of the FSMDs
• Be able to travel to the NIH Clinical Center at the NIH for studies
• Able to commit to multiple 5 day stays at the NIH Clinical Center
• Established primary care physician
• Ambulant: able to walk 10 meters or 33 feet without walking aids or orthotics

EXCLUSION CRITERIA:

• Fail to meet the above inclusion criteria
• Are unable or unwilling to be examined
• Adults unable to provide their own consent
• Have active, on-going medical problems such as (e.g. diabetes, hypothyroidism, pancreatitis, anemia, cancer, renal, hepatic, Pulmonary or cardiac disease) or who have undergone recent surgery (i.e. less than 8 days post-surgery)
• Pregnant females
• Currently taking any or a combination of anti-inflammatory drugs, statins or other drugs with known myotoxicity, narcotics

Contacts and Locations

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Locations

United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892

Sponsors and Collaborators

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

National Institute of Neurological Disorders and Stroke (NINDS)

National Institutes of Health Clinical Center (CC)

University of Massachusetts, Worcester

Investigators

Principal Investigator:	Joshua J Zimmerberg, M.D.	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

More Information

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Additional Information:

NIH Clinical Center Detailed Web Page 

Publications:

Bansal D, Campbell KP. Dysferlin and the plasma membrane repair in muscular dystrophy. Trends Cell Biol. 2004 Apr;14(4):206-13. Review.

Cohn RD, Campbell KP. Molecular basis of muscular dystrophies. Muscle Nerve. 2000 Oct;23(10):1456-71. Review.

Wallace GQ, McNally EM. Mechanisms of muscle degeneration, regeneration, and repair in the muscular dystrophies. Annu Rev Physiol. 2009;71:37-57. doi: 10.1146/annurev.physiol.010908.163216. Review.

Responsible Party:	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier:	NCT01851447 History of Changes
Other Study ID Numbers:	130112; 13-CH-0112
First Posted:	May 10, 2013
Last Update Posted:	May 2, 2018
Last Verified:	April 30, 2018

Keywords provided by National Institutes of Health Clinical Center (CC) ( Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) ):

Muscle; Inflammatory Cytokines; Exercise; Biomarkers; Predictors of Outcome

Additional relevant MeSH terms:

Muscular Dystrophies; Genetic Diseases, Inborn; Muscular Disorders, Atrophic; Muscular Diseases	Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases