Skeletal Muscle Biomarkers in People With Fragile Sarcolemmal Muscular Dystrophy

Pilot Study to Assess Biomarkers of Changes in Barrier Function of Skeletal Muscle in Patients With a Fragile Sarcolemmal Muscular Dystrophy

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.

Study Overview

• Status: Active, not recruiting
• Conditions: 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).

Study Phase: 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 Type: Observational
• Enrollment (Actual): 11

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • National Institutes of Health Clinical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

11 patients, 18 years or older with early adulthood or later onset of a genetically diagnosed FSMD will be enrolled in this study. We estimate no more than 50 patients to be eligible for enrollment. This pilot study will accept a maximum of 11 patients.

Description

• 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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Fragile Sarcolemmal Muscular Dystrophy; patients with early adulthood or late onset of a genetic disorder FSMD (LGMD 2B-F, I, L, MM, BMD and MMD3)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
changes in biomarker levels	biomarker levels (CK, ALT, AST...) increases	early in the morning, before and after morning activities
changes in biomarker levels	biomarker levels (CK, ALT, AST...) increase	after physical exercise, strength test under guidance of physical therapist

Collaborators and Investigators

• Sponsor: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Collaborators: National Institutes of Health Clinical Center (CC); National Institute of Neurological Disorders and Stroke (NINDS); University of Massachusetts, Worcester
• Investigators: Principal Investigator: Joshua J Zimmerberg, M.D., Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Publications and helpful links

Helpful Links

• NIH Clinical Center Detailed Web Page

Study record dates

Study Major Dates

• Study Start (Actual): November 3, 2014
• Primary Completion (Estimated): December 31, 2024
• Study Completion: December 31, 2023

Study Registration Dates

• First Submitted: May 9, 2013
• First Submitted That Met QC Criteria: May 9, 2013
• First Posted (Estimated): May 10, 2013

Study Record Updates

• Last Update Posted (Estimated): April 26, 2024
• Last Update Submitted That Met QC Criteria: April 25, 2024
• Last Verified: January 17, 2024

More Information

Terms related to this study

• Keywords: Exercise; Natural History; Inflammatory Cytokines; Membrane Wound; Plasma Membrane Repair; Predictors of Outcome
• Additional Relevant MeSH Terms: Nervous System Diseases; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Muscular Disorders, Atrophic; Muscular Dystrophies; Genetic Diseases, Inborn
• Other Study ID Numbers: 130112; 13-CH-0112

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No