Defining Clinical Endpoints in Limb Girdle Muscular Dystrophy (LGMD) (GRASP-01-001)

September 11, 2023 updated by: Virginia Commonwealth University

GRASP-LGMD: Defining Clinical Endpoints in 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.

Study Overview

Status

Recruiting

Conditions

Detailed Description

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.

Study Type

Observational

Enrollment (Estimated)

80

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United Kingdom
      • Newcastle, United Kingdom
      • Newcastle Upon Tyne, United Kingdom
        • Recruiting
        • John Walton Muscular Dystrophy Research Centre (Newcastle upon Tyne)
        • Principal Investigator:
          • Jordi Diaz-Manera, MD
        • Contact:
  • United States
    • California
      • Irvine, California, United States, 92697
        • Recruiting
        • University of California Irvine
        • Principal Investigator:
          • Tahseen Mozaffar, MD
        • Contact:
        • Contact:
    • Colorado
      • Aurora, Colorado, United States, 80045
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • Recruiting
        • University of Iowa
        • Principal Investigator:
          • Kathryn Mathews, MD
        • Contact:
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • Recruiting
        • Kansas University Medical Center
        • Contact:
        • Principal Investigator:
          • Jeffrey Statland, MD
        • Contact:
    • Maryland
      • Baltimore, Maryland, United States, 21205
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • Recruiting
        • University of Minnesota
        • Contact:
        • Contact:
        • Principal Investigator:
          • Peter B Kang, MD
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Recruiting
        • Washington University School of Medicine
        • Principal Investigator:
          • Conrad Weihl, MD
        • Contact:
        • Contact:
    • Ohio
      • Columbus, Ohio, United States, 43205
    • Virginia

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

4 years to 65 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

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.

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Other

Cohorts and Interventions

Group / Cohort
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Baseline to 12 months
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.
Baseline to 12 months
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.
Baseline to 12 months
Change in workspace volume
Time Frame: Baseline to 12 months
Workspace volume (WSV) will be measured using ACTIVE, an interactive video game which will calculate the combination of upper extremity and trunk strength and function in cubic meters.
Baseline to 12 months
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
Baseline to 12 months
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
Baseline to 12 months
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.
Baseline to 12 months
Change in upper extremity disability
Time Frame: Baseline to 12 months
The Disabilities of the Arm, Shoulder, and Hand Questionnaire (DASH) questionnaire measures levels of disability in an individual's upper extremity.
Baseline to 12 months
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.
Baseline to 12 months
Change in self-reported mental health
Time Frame: Baseline to 12 months
PROMIS Mental Health is part of a set of patient-reported measures developed by a National Institute of Health that evaluates general mental health by assessing anxiety, depression, alcohol use, anger, cognitive function, life satisfaction, meaning and purpose, positive affect, psychosocial illness impact, self-efficacy for managing chronic conditions, smoking, and substance use
Baseline to 12 months
Change in self-reported social health
Time Frame: Baseline to 12 months
PROMIS Social Health is part of a set of patient-reported measures developed by a National Institute of Health that evaluates general social health by assessing ability to participate in social roles and activities, companionship, satisfaction with social roles and activities, social isolation, and social support.
Baseline to 12 months
Change in whole body health
Time Frame: Baseline to 12 months
The Quality of Life in Genetic Neuromuscular Disease Questionnaire was developed to measure whole-body health impact in neuromuscular diseases.
Baseline to 12 months
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.
Baseline to 12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Virginia Commonwealth University

Collaborators

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

Investigators

  • Principal Investigator: Nicholas Johnson, MD, Virginia Commonwealth University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 14, 2019

Primary Completion (Estimated)

June 30, 2024

Study Completion (Estimated)

June 30, 2024

Study Registration Dates

First Submitted

June 3, 2019

First Submitted That Met QC Criteria

June 7, 2019

First Posted (Actual)

June 10, 2019

Study Record Updates

Last Update Posted (Actual)

September 13, 2023

Last Update Submitted That Met QC Criteria

September 11, 2023

Last Verified

September 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HM20018721
  • GRASP-LGMD (Other Identifier: Virginia Commonwealth University)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Aggregated and deidentified data will be shared with qualified investigators upon majority approval of the LGMD investigators

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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