Defining Clinical Endpoints in Limb Girdle Muscular Dystrophy (LGMD)

NCT03981289 | Completed DMC

• 2 other identifiers: HM20018721GRASP-LGMD
• Study Type: observational
• Target: 116
• Locations: 2 countries
• Sites: 10

Brief Summary

Limb Girdle Muscular Dystrophy comprise a group of disorders made up of over 30 mutations which share a common phenotype of progressive weakness of the shoulder and hip girdle muscles. While the individual genetic mutations are rare, as a cohort, LGMDs are one of the four most common muscular dystrophies. The overall goal of project 1 is to define the key phenotypes as measured by standard clinical outcome assessments (COAs) for limb girdle muscular dystrophies (LGMD) to hasten therapeutic development.

Conditions

Limb Girdle Muscular Dystrophy; Muscular Dystrophies

Keywords

LGMD; Limb Girdle Muscular Dystrophy; CAPN3; ANO5; DYSF; DNAJB6; Sarcoglycan; SGCA; SGCB; SGCD; SGCG

Outcome Measures

Primary Outcomes (8)

• Change in mobility

  Mobility will be measured using the 100 Meter Timed Test (100m) in which the participant is asked to complete 2 laps around 2 cones set 25 meters apart as quickly as safely possible, running if able, and the time in seconds is recorded.

  Baseline to 12 months

• Change in motor performance

  The North Star Assessment for Dysferlinopathy (NSAD) is a functional scale specifically designed to measure motor performance in individuals with LGMD. It consists of 29 items that are considered clinically relevant items from the North Star Ambulatory Assessment and the Motor Function Measure 20 with a maximum score of 54 and higher scores indicate higher functional abilities.

  Baseline to 12 months

• Change in upper limb function characteristics

  The Performance of Upper Limb 2.0 (PUL) scale measures the progression of weakness and natural history of functional decline in Duchenne muscular dystrophy. There are 22 scored items; a score of 42 indicates the highest level of independent function and 0 the lowest.

  Baseline to 12 months

• Change in Forced vital capacity (FVC)

  Volume of air forcefully exhaled will be measured using Spirometry performed in a sitting position using standardized equipment

  Baseline to 12 months

• Changes in Forced expiratory volume (FEV1)

  Volume of air forcefully exhaled in one second will be measured using Spirometry performed in a sitting position using standardized equipment

  Baseline to 12 months

• Change in activity limitations

  ACTIVLIM is a patient-reported measure of activity limitations for individuals with upper and/or lower limb impairments, which measures the ability to perform daily activities.

  Baseline to 12 months

• Change in self-reported physical health

  PROMIS Physical Health is part of a set of patient-reported measures developed by a National Institute of Health that evaluates general physical health by assessing fatigue, pain intensity, pain interference, physical function, sleep disturbance, dyspnea, gastrointestinal symptoms, itch, pain behavior, pain quality, sexual function, and sleep related impairment.

  Baseline to 12 months

• Change in overall health

  Domain Delta Questionnaire is a patient reported measure that assesses overall health over the previous 12 months.

  Baseline to 12 months

Study Arms (5)

CAPN3 (LGMD2A)

Clinical Assessments, Biomarkers

DYSF (LGMD2B)

Clinical Assessments, Biomarkers

ANO5 (LGMD2L)

Clinical Assessments, Biomarkers

DNAJB6 (LGMD1D)

Clinical Assessments, Biomarkers

Sarcoglycan (LGMD2D) (LGMD2E) (LGMD2C) (LGMD2F)

Clinical assessments

Eligibility Criteria

• Age: 4 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

GRASP-LGMD covers a broad geographical distribution and we expect the race and ethnicity to match that of the United States. However, past experience in both the clinical and research LGMD populations shows that some minority subgroups are under-represented in research studies. To assist with recruitment of persons from diverse backgrounds we will utilize the Community and Special Populations Engagement Personnel supported through the CTSA networks to reach out to under-represented communities through a variety of local techniques which could include direct outreach, advertising with local advocacy groups, organizations, or newsletters, and local advertising using a variety of media which could include Social Media (e.g. Facebook, Twitter), radio, and newspapers.

You may qualify if:

• Age between 4-65 at enrollment
• Clinically affected (defined as weakness on bedside evaluation in either a limb-girdle pattern, or in a distal extremity)
• A genetically or functionally confirmed mutation in ANO5, CAPN3, DYSF, DNAJB6 or SGCA-G.
• Willing and able to give informed consent and follow all study procedures and requirements
• Age between 4-65 at enrollment
• Clinically affected (defined as weakness on bedside evaluation in either a limb-girdle pattern, or in a distal extremity)
• a genetically confirmed mutation in SGCA-G
• Willing and able to give informed consent and follow all study procedures and requirements

You may not qualify if:

• Any other illness that would interfere with the ability to undergo safe testing or would interfere with interpretation of the results in the opinion of the site investigator.
• History of a bleeding disorder, platelet count \<50,000, current use of an anticoagulant.
• Positive pregnancy test at time any timepoint during the trial.
• Any other illness that would interfere with the ability to undergo safe testing or would interfere with interpretation of the results in the opinion of the site investigator.
• History of a bleeding disorder, platelet count \<50,000, current use of an anticoagulant
• Positive pregnancy test at time any timepoint during the trial.

Sponsors & Collaborators

• Washington University School of Medicine: collaborator
• University of Minnesota: collaborator
• University of California, Irvine: collaborator
• Hugo W. Moser Research Institute at Kennedy Krieger, Inc.: collaborator
• Virginia Commonwealth University: lead
• Newcastle University: collaborator
• Nationwide Children's Hospital: collaborator
• University of Iowa: collaborator
• University of Colorado, Denver: collaborator
• University of Kansas Medical Center: collaborator

Study Sites (10)

University of California Irvine

Irvine, California, 92697, United States

Location

The University of Colorado Anschutz Medical Campus

Aurora, Colorado, 80045, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Kennedy Krieger Institute

Baltimore, Maryland, 21205, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

John Walton Muscular Dystrophy Research Centre (Newcastle Upon Tyne)

Newcastle, United Kingdom

Location

Related Publications (2)

• Doody A, Alfano L, Diaz-Manera J, Lowes L, Mozaffar T, Mathews KD, Weihl CC, Wicklund M, Hung M, Statland J, Johnson NE; GRASP-LGMD Consortium. Defining clinical endpoints in limb girdle muscular dystrophy: a GRASP-LGMD study. BMC Neurol. 2024 Mar 15;24(1):96. doi: 10.1186/s12883-024-03588-1.

  PMID: 38491364 DERIVED

• Doody A, Alfano L, Diaz-Manera J, Lowes L, Mozaffar T, Mathews K, Weihl CC, Wicklund M, Statland J, Johnson NE; GRASP-LGMD Consortium. Defining Clinical Endpoints in Limb Girdle Muscular Dystrophy: A GRASP-LGMD study. Res Sq [Preprint]. 2023 Oct 6:rs.3.rs-3370395. doi: 10.21203/rs.3.rs-3370395/v1.

  PMID: 37886601 DERIVED

MeSH Terms

Conditions

Muscular Dystrophies, Limb-Girdle; Muscular Dystrophies; Muscular Dystrophy, Limb-Girdle, Type 1D

Condition Hierarchy (Ancestors)

Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Nicholas Johnson, MD

  Virginia Commonwealth University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 3, 2019
• First Posted: June 10, 2019
• Study Start: June 14, 2019
• Primary Completion: June 30, 2025
• Study Completion: June 30, 2025
• Last Updated: February 27, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (9); GB (1)