Calpain-3 Deficiency Limb Girdle Muscular Dystrophy Type 2A, LGMD2A, Limb Girdle Muscular Dystrophy, Limb Girdle Muscular Dystrophy Type R1
Conditions
Keywords
LGMD, Limb Girdle Muscular Dystrophy, LGMD R1, LGMD2A, CAPN3
Brief summary
This is a 24-month, observational study of 100 participants with Limb Girdle Muscular Dystrophy type R1, also known as CAPN3.
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.
Interventions
None listed
Sponsors
Virginia Commonwealth University
Nationwide Children's Hospital
Washington University School of Medicine
University of Iowa
University of Florida
University of Minnesota
Newcastle University
University of Kansas Medical Center
University of Colorado, Denver
Indiana CHC (Community Health Clinic)
University of California, Irvine
Study design
Observational model
COHORT
Time perspective
OTHER
Eligibility
Sex/Gender
ALL
Age
12 Years to 50 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORNicholas Johnson, MD
Virginia Commonwealth University
Outcome results
None listed