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GRASP-01-003: Trial Readiness and Endpoint Assessment in LGMD R1

Sponsor
Virginia Commonwealth University (Other)
Overall Status
Not yet recruiting
CT.gov ID
NCT05618080
Collaborator
University of California, Irvine (Other), University of Kansas (Other), University of Colorado, Denver (Other), Nationwide Children's Hospital (Other), Washington University School of Medicine (Other), University of Iowa (Other), University of Florida (Other), University of Minnesota (Other)
100
Enrollment
1
Location
63
Anticipated Duration (Months)
1.6
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a 24-month, observational study of 100 participants with Limb Girdle Muscular Dystrophy type R1, also known as CAPN3.

Condition or Disease Intervention/Treatment Phase

    Detailed Description

    Limb girdle muscular dystrophies (LGMD) are a group of over 30 heterogenous genetic disorders which have in common a pattern of weakness affecting proximal muscles of the shoulders and hips. LGMD type R1 (LGMDR1; also LGMD2A) is due to loss of function of the muscle structural gene calpain 3 (CAPN3) and causes progressive weakness and muscle wasting, which can lead to loss of ambulation or the ability to maintain a job. LGMDR1 is one of the most common LGMDs in the United States and has no FDA approved therapies but is amenable to gene replacement strategies, regenerative medicine approaches, or myostatin based approaches. There have been rapid advances in gene delivery therapies for Duchenne Muscular Dystrophy and for LGMDR4 that have set the stage for targeted therapeutic development for all LGMDs, and LGMDR1 in particular is at a crossroads: the pace of therapeutic development has outstripped the efforts at clinical trial preparedness.

    There is a need for a more rigorous natural history study to assist in the design of clinical trials; in particular, identifying biomarkers for early phase development and clinical outcome assessments (COAs) for drug approval studies.

    This study will enroll 100 subjects across participating sites in the GRASP-LGMD Research Consortium. No treatment will be administered as part of this study. A subset of 80 patients will undergo MR scans at selected imaging sites. Study visits will occur at Baseline Day 1, Baseline Day 2, Month 12, and Month 24.

    Study Design

    Study Type:
    Observational
    Anticipated Enrollment :
    100 participants
    Observational Model:
    Cohort
    Time Perspective:
    Other
    Official Title:
    GRASP-01-003: Trial Readiness and Endpoint Assessment in LGMD R1
    Anticipated Study Start Date :
    Mar 5, 2023
    Anticipated Primary Completion Date :
    Mar 5, 2028
    Anticipated Study Completion Date :
    Jun 5, 2028

    Arms and Interventions

    Arm Intervention/Treatment
    LGMD Type R1/LGMD2A/CAPN3

    No intervention will be administered.

    Outcome Measures

    Primary Outcome Measures

    1. Validate the NSAD as a clinical outcome assessment in LGMD R1 [Baseline to 24 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.

    Secondary Outcome Measures

    1. Validate muscle fat fraction as a biomarker [Baseline to 12 months]

      Quantitative muscle MRI (qMR) of the upper and lower leg muscles will be performed and muscle fat fraction will be measured.

    Other Outcome Measures

    1. Change in mobility (100-meter walk) [Baseline to 24 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 Forced vital capacity (FVC) [Baseline to 24 months]

      Volume of air forcefully exhaled will be measured using Spirometry performed in sitting and supine positions using standardized equipment

    3. Change in Forced expiratory volume (FEV1) [Baseline to 24 months]

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

    4. Change in upper limb function characteristics (PUL) [Baseline to 24 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.

    5. Change in Timed Up-And-Go (TUG) [Baseline to 24 months]

      Time to stand from a chair, walk 3 meters, and return to seated will be recorded. The test will be repeated three times at applicable visits.

    6. Change in 4 Stair Climb [Baseline to 24 months]

      Time to ascend 4 steps as quickly and safely as possible, using handrails if needed, will be assessed.

    7. Change in Handheld Dynamometry and Pinch Grip [Baseline to 24 months]

      Maximum hand, pinch, and grip strength will be assessed using a myometer. The participant will be asked to squeeze a handheld tool.

    8. Change in self-reported social, mental, and physical health (PROMIS-57) [Baseline to 24 months]

      PROMIS is a set of patient-reported measures developed by the NIH. The social health set of questions 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. The mental health set 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. The physical health set 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.

    9. Change in activity limitations (ACTLIVLIM) [Baseline to 24 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.

    10. Change in overall health (Domain Delta) [Baseline to 24 months]

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

    11. Change in overall health-related quality of life (LGMD-HI) [Baseline to 24 months]

      The LGMD Health Index is a disease-specific, patient reported measure that assesses overall health-related quality of life in LGMD.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    12 Years to 50 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Age between 12-50 at enrollment

    • Clinically affected (defined as weakness on bedside evaluation in a pattern consistent with LGMDR1)

    • Genetic confirmation of LGMDR1 (presence of homozygous or compound heterozygous pathogenic mutations in CAPN3).

    Exclusion Criteria:

    • Have contraindications to MRI or MRS (e.g., non-MR compatible implanted medical devices or severe claustrophobia)

    • Non-ambulatory as defined by those who are not able to walk 10 meters without assistive devices (AFOs excluded)

    • 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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Virginia Commonwealth University Richmond Virginia United States 23298

    Sponsors and Collaborators

    • Virginia Commonwealth University
    • University of California, Irvine
    • University of Kansas
    • University of Colorado, Denver
    • Nationwide Children's Hospital
    • Washington University School of Medicine
    • University of Iowa
    • University of Florida
    • University of Minnesota

    Investigators

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

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Virginia Commonwealth University
    ClinicalTrials.gov Identifier:
    NCT05618080
    Other Study ID Numbers:
    • HM20025359
    • GRASP-LGMDR1
    • GRASP-R1
    First Posted:
    Nov 16, 2022
    Last Update Posted:
    Jan 11, 2023
    Last Verified:
    Jan 1, 2023
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    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
    LGMD R1
    LGMD2A
    CAPN3
    Additional relevant MeSH terms:
    Muscular Dystrophies
    Muscular Dystrophies, Limb-Girdle

    Study Results

    No Results Posted as of Jan 11, 2023