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Completed

NCT Number: NCT03981289

Defining Clinical Endpoints in Limb Girdle Muscular Dystrophy (LGMD)

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.

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Key information

Conditions

Limb Girdle Muscular Dystrophy Congenital, Hereditary, and Neonatal Diseases and Abnormalities Genetic Diseases, Inborn Muscular Diseases Muscular Disorders, Atrophic Muscular Dystrophies Muscular Dystrophies, Limb-Girdle Muscular Dystrophy, Limb-Girdle, Type 1D Musculoskeletal Diseases Nervous System Diseases Neuromuscular Diseases

Age range

4 year–65 year

Sex eligibility

All sexes

Study type

Observational

Primary location

John Walton Muscular Dystrophy Research Centre (Newcastle Upon Tyne), Newcastle, United Kingdom

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About this study

The genetic heterogeneity has been a barrier to broad natural history efforts, with prior investigations often limited to single gene mutations. Much attention is paid to the variability within individual mutations (e.g. distal presentations), as opposed to defining the best strategy for measuring change in overall LGMD disease burden. This presents a major dilemma for LGMD rare disease research: how to balance diverse genes leading to overlapping phenotypes, versus variants in the same gene leading to divergent phenotypes. What is clear, is as a group, LGMDs are chronic and progressive leading to significant lifetime morbidity and represent a large unmet clinical need.

Recent developments in the investigator's genetic understanding of LGMD and molecular approaches to therapy have led to proposed gene replacement therapies for at least three of the LGMD mutations. Several of these gene replacement therapies are currently in pre-clinical/phase 1 testing, leading to an urgent need for natural history data. In addition, non-specific therapies which target muscle mass or function are being tested in other muscular dystrophies and may prove beneficial for LGMD.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

- Arm 1:

  • 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

Inclusion criteria

- Arm 2:

  • 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

Exclusion criteria

- Arm 1:

  • 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.

Exclusion criteria

- Arm 2:

  • 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.

Treatment and study plan

Primary outcomes

  1. Change in mobility

    Time frame: Baseline to 12 months

    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.

  2. Change in motor performance

    Time frame: Baseline to 12 months

    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.

  3. Change in upper limb function characteristics

    Time frame: Baseline to 12 months

    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.

  4. Change in Forced vital capacity (FVC)

    Time frame: Baseline to 12 months

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

  5. Changes in Forced expiratory volume (FEV1)

    Time frame: Baseline to 12 months

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

  6. Change in activity limitations

    Time frame: Baseline to 12 months

    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.

  7. Change in self-reported physical health

    Time frame: Baseline to 12 months

    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.

  8. Change in overall health

    Time frame: Baseline to 12 months

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

Sponsors and collaborators

Lead sponsor

Virginia Commonwealth University

Other

Collaborators

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

Registry information

Official study title

GRASP-LGMD: Defining Clinical Endpoints in LGMD

Acronym: GRASP-01-001

Important dates

Study start
2019
Primary completion
2025
Study completion
2025
First posted
Jun 10, 2019
Registry last updated
Feb 27, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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