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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03981289
Recruitment Status : Recruiting
First Posted : June 10, 2019
Last Update Posted : February 3, 2023
Sponsor:
Collaborators:
Newcastle University
University of California, Irvine
University of Kansas
University of Colorado Anschutz Medical Center
Nationwide Children's Hospital
Washington University School of Medicine
University of Iowa
Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
University of Minnesota
Information provided by (Responsible Party):
Virginia Commonwealth University

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.

Condition or disease
Limb Girdle Muscular Dystrophy Muscular Dystrophies

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.

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Study Type : Observational
Estimated Enrollment : 80 participants
Observational Model: Cohort
Time Perspective: Other
Official Title: GRASP-LGMD: Defining Clinical Endpoints in LGMD
Actual Study Start Date : June 14, 2019
Estimated Primary Completion Date : June 30, 2024
Estimated Study Completion Date : June 30, 2024


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



Primary Outcome Measures :
  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 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.

  5. 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

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. 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.

  13. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   4 Years to 65 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
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.
Criteria

Inclusion Criteria:

  • 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.
  • Ambulatory

Exclusion Criteria:

  • Non-ambulatory at the time of enrollment.
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03981289


Contacts
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Contact: Ruby Langeslay 804-828-8481 Ruby.Langeslay@vcuhealth.org
Contact: Jennifer Raymond 804-828-6318 Jennifer.Raymond@vcuhealth.org

Locations
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United States, California
University of California Irvine Recruiting
Irvine, California, United States, 92697
Contact: Lauren Harris    714-509-2661    lnharri1@hs.uci.edu   
Contact: Isela Hernandez    714-509-2664    iselah@hs.uci.edu   
Principal Investigator: Tahseen Mozaffar, MD         
United States, Colorado
The University of Colorado Anschutz Medical Campus Recruiting
Aurora, Colorado, United States, 80045
Contact: Alyssa Avilez       alyssa.avilez@cuanschutz.edu   
Contact: Brianna Blume    303-724-6386    brianna.blume@cuanschutz.edu   
Principal Investigator: Matthew Wicklund, MD         
United States, Florida
University of Florida Recruiting
Gainesville, Florida, United States, 32608
Contact: Sarah Barbey    352-273-5085    sarah.barbey@peds.ufl.edu   
Principal Investigator: Peter Kang, MD         
United States, Iowa
University of Iowa Recruiting
Iowa City, Iowa, United States, 52242
Contact: Carrie Stephan    319-356-2673    carrie-stephan@uiowa.edu   
Principal Investigator: Kathryn Mathews, MD         
United States, Kansas
Kansas University Medical Center Recruiting
Kansas City, Kansas, United States, 66160
Contact: Michaela Walker, MD    913-945-9920    mwalker20@kumc.edu   
Contact: Rebecca Clay    913-945-9936    rclay@kumc.edu   
Principal Investigator: Jeffrey Statland, MD         
United States, Maryland
Kennedy Krieger Institute Recruiting
Baltimore, Maryland, United States, 21205
Contact: Georgina DSanson       Dsanson@kennedykrieger.org   
Contact: Genila Bibat    443-923-2697    bibat@kennedykrieger.org   
Principal Investigator: Doris Leung, MD         
United States, Minnesota
University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Allison Johnston       joh21779@umn.edu   
Contact: John Martone       marto045@umn.edu   
Principal Investigator: Peter B Kang, MD         
United States, Missouri
Washington University School of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Michelle Seiffert    314-273-7946    mseiffert@wustl.edu   
Contact: Stephanie Poelker       spoelker@wustl.edu   
Principal Investigator: Conrad Weihl, MD         
United States, Ohio
Nationwide Children's Hospital Recruiting
Columbus, Ohio, United States, 43205
Contact: Madison Schmelzer    614-722-6941    madison.schmelzer@nationwidechildrens.org   
Contact: Randa Mireb    614-355-3508    randa.mireb@nationwidechildrens.org   
Principal Investigator: Linda Lowes         
United States, Virginia
Virginia Commonwealth University Recruiting
Richmond, Virginia, United States, 23298
Contact: Abel Bulti       abel.bulti@vcuhealth.org   
Contact: Anarosa Rezeq       anarosa.rezeq@vcuhealth.org   
Principal Investigator: Nicholas Johnson, MD         
United Kingdom
Newcastle University Recruiting
Newcastle, United Kingdom
Contact: Nicola McLarty       nicola.mclarty1@nhs.net   
Contact: Dana Gergely       dana.gergely@newcastle.ac.uk   
Principal Investigator: Jordi Diaz-Manera, MD         
Sponsors and Collaborators
Virginia Commonwealth University
Newcastle University
University of California, Irvine
University of Kansas
University of Colorado Anschutz Medical Center
Nationwide Children's Hospital
Washington University School of Medicine
University of Iowa
Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
University of Minnesota
Investigators
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Principal Investigator: Nicholas Johnson, MD Virginia Commonwealth University
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Responsible Party: Virginia Commonwealth University
ClinicalTrials.gov Identifier: NCT03981289    
Other Study ID Numbers: HM20018721
GRASP-LGMD ( Other Identifier: Virginia Commonwealth University )
First Posted: June 10, 2019    Key Record Dates
Last Update Posted: February 3, 2023
Last Verified: January 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Aggregated and deidentified data will be shared with qualified investigators upon majority approval of the LGMD investigators

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Virginia Commonwealth University:
LGMD
Limb Girdle Muscular Dystrophy
CAPN3
AN05
DYSF
DNAJB6
Sarcoglycan
SGCA
SGCB
SGCD
SGCG
Additional relevant MeSH terms:
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Muscular Dystrophies
Muscular Dystrophies, Limb-Girdle
Muscular Disorders, Atrophic
Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Diseases
Nervous System Diseases
Genetic Diseases, Inborn