LGMD R1 Natural History Study (GRASP-01-003)

June 6, 2025 updated by: Virginia Commonwealth University

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

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

Study Overview

Status

Recruiting

Conditions

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 Type

Observational

Enrollment (Estimated)

100

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

  • Netherlands
  • United Kingdom
      • Newcastle Upon Tyne, United Kingdom
        • Not yet recruiting
        • Newcastle University
        • Principal Investigator:
          • Jordi Diaz-Manera, MD, PhD
        • Contact:
  • United States
    • California
      • Orange, California, United States, 92868
        • Recruiting
        • University of California, Irvine
        • Principal Investigator:
          • Tahseen Mozaffar, MD
        • Contact:
        • Contact:
    • Colorado
    • Florida
      • Gainesville, Florida, United States, 32610
        • Not yet recruiting
        • University of Florida
        • Principal Investigator:
          • Sub Subramony, MD
        • Contact:
    • Indiana
      • Shipshewana, Indiana, United States, 46565
        • Recruiting
        • The Community Health Clinic, Inc.
        • Principal Investigator:
          • Zineb Ammous, MD, FACMG
        • Contact:
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • Recruiting
        • University of Iowa Hospitals and Clinics
        • Principal Investigator:
          • Katherine Mathews, MD
        • Contact:
        • Contact:
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • Recruiting
        • University of Kansas Medical Center
        • Principal Investigator:
          • Jeffrey Statland, MD
        • Contact:
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • Recruiting
        • University of Minnesota, Department of Neurology
        • Principal Investigator:
          • Peter Kang, MD
        • Contact:
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Recruiting
        • Washington University School of Medicine
        • Contact:
        • Principal Investigator:
          • Conrad Weihl, MD, PhD
    • Ohio
    • 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

12 years to 50 years (Child, Adult)

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

The study population includes ambulatory individuals aged 12-50 at enrollment who are clinically affected by and have genetic confirmation of LGMDR1.

Description

Inclusion Criteria:

  1. Age between 12-50 at enrollment
  2. Clinically affected (defined as weakness on bedside evaluation in a pattern consistent with LGMDR1)
  3. Genetic confirmation of LGMDR1 (presence of homozygous or compound heterozygous pathogenic mutations in CAPN3).
  4. Must be able to provide written informed consent and be willing and able to comply with all study requirements. Note: Adult participants must be able to provide consent themselves. Legally authorized representatives are not permitted to consent on behalf of adult participants.

Exclusion Criteria:

  1. Have contraindications to MRI or MRS (e.g., non-MR compatible implanted medical devices or severe claustrophobia)
  2. Non-ambulatory as defined by those who are not able to walk 10 meters without assistive devices (ankle foot orthotics excluded)
  3. Positive pregnancy test at any timepoint during the trial
  4. Have dominantly inherited CAPN3 mutations (LGMDD4)
  5. 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.

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
LGMD Type R1/LGMD2A/CAPN3
No intervention will be administered.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Validate the NSAD as a clinical outcome assessment in LGMD R1
Time Frame: 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.
Baseline to 24 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Validate muscle fat fraction as a biomarker
Time Frame: 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.
Baseline to 12 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in mobility (100-meter walk)
Time Frame: 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.
Baseline to 24 months
Change in Forced vital capacity (FVC)
Time Frame: Baseline to 24 months
Volume of air forcefully exhaled will be measured using Spirometry performed in sitting and supine positions using standardized equipment
Baseline to 24 months
Change in Forced expiratory volume (FEV1)
Time Frame: 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
Baseline to 24 months
Change in upper limb function characteristics (PUL)
Time Frame: 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.
Baseline to 24 months
Change in Timed Up-And-Go (TUG)
Time Frame: 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.
Baseline to 24 months
Change in 4 Stair Climb
Time Frame: Baseline to 24 months
Time to ascend 4 steps as quickly and safely as possible, using handrails if needed, will be assessed.
Baseline to 24 months
Change in Handheld Dynamometry and Pinch Grip
Time Frame: 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.
Baseline to 24 months
Change in self-reported social, mental, and physical health (PROMIS-57)
Time Frame: 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.
Baseline to 24 months
Change in activity limitations (ACTLIVLIM)
Time Frame: 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.
Baseline to 24 months
Change in overall health (Domain Delta)
Time Frame: Baseline to 24 months
Domain Delta Questionnaire is a patient reported measure that assesses overall health over the previous 12 months.
Baseline to 24 months
Change in overall health-related quality of life (LGMD-HI)
Time Frame: 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.
Baseline to 24 months

Collaborators and Investigators

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

Sponsor

Virginia Commonwealth University

Collaborators

University of Colorado, Denver
Washington University School of Medicine
University of Iowa
University of Florida
University of Kansas Medical Center
University of Minnesota
Nationwide Children's Hospital
University of California, Irvine
Newcastle University
Indiana CHC (Community Health Clinic)

Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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)

January 31, 2024

Primary Completion (Estimated)

May 1, 2028

Study Completion (Estimated)

August 1, 2028

Study Registration Dates

First Submitted

November 9, 2022

First Submitted That Met QC Criteria

November 9, 2022

First Posted (Actual)

November 16, 2022

Study Record Updates

Last Update Posted (Actual)

June 8, 2025

Last Update Submitted That Met QC Criteria

June 6, 2025

Last Verified

June 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HM20025359
  • GRASP-R1 (Other Identifier: Virginia Commonwealth University)
  • Limb-Girdle Muscular Dystrophy (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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