Study Results
Results pending
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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Recruitment Status
RECRUITING
Total Enrollment
100 participants
Study Classification
OBSERVATIONAL
Study Start Date
2024-01-31
Study Completion Date
2028-08-31
Brief Summary
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This is a 24-month, observational study of 100 participants with Limb Girdle Muscular Dystrophy type R1, also known as CAPN3.
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Detailed Description
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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.
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.
Conditions
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Calpain-3 Deficiency Limb Girdle Muscular Dystrophy Type 2A
Limb Girdle Muscular Dystrophy
Limb Girdle Muscular Dystrophy Type R1
LGMD2A
Study Design
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Observational Model Type
COHORT
Study Time Perspective
OTHER
Study Groups
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LGMD Type R1/LGMD2A/CAPN3
No intervention will be administered.
No interventions assigned to this group
Eligibility Criteria
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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.
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.
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.
Minimum Eligible Age
12 Years
Maximum Eligible Age
50 Years
Eligible Sex
ALL
Accepts Healthy Volunteers
No
Sponsors
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Nationwide Children's Hospital
OTHER
Sponsor Role
collaborator
Washington University School of Medicine
OTHER
Sponsor Role
collaborator
University of Iowa
OTHER
Sponsor Role
collaborator
University of Florida
OTHER
Sponsor Role
collaborator
University of Minnesota
OTHER
Sponsor Role
collaborator
Newcastle University
OTHER
Sponsor Role
collaborator
University of Kansas Medical Center
OTHER
Sponsor Role
collaborator
University of Colorado, Denver
OTHER
Sponsor Role
collaborator
Indiana CHC (Community Health Clinic)
UNKNOWN
Sponsor Role
collaborator
University of California, Irvine
OTHER
Sponsor Role
collaborator
Virginia Commonwealth University
OTHER
Sponsor Role
lead
Responsible Party
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Responsibility Role
SPONSOR
Principal Investigators
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Nicholas Johnson, MD
Role: PRINCIPAL_INVESTIGATOR
Virginia Commonwealth University
Locations
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University of California, Irvine
Orange, California, United States
Site Status
RECRUITING
University of Colorado Anschutz Medical Campus
Aurora, Colorado, United States
Site Status
RECRUITING
University of Florida
Gainesville, Florida, United States
Site Status
NOT_YET_RECRUITING
The Community Health Clinic, Inc.
Shipshewana, Indiana, United States
Site Status
RECRUITING
University of Iowa Hospitals and Clinics
Iowa City, Iowa, United States
Site Status
RECRUITING
University of Kansas Medical Center
Kansas City, Kansas, United States
Site Status
RECRUITING
University of Minnesota, Department of Neurology
Minneapolis, Minnesota, United States
Site Status
RECRUITING
Washington University School of Medicine
St Louis, Missouri, United States
Site Status
RECRUITING
Nationwide Children's Hospital
Columbus, Ohio, United States
Site Status
RECRUITING
Virginia Commonwealth University
Richmond, Virginia, United States
Site Status
RECRUITING
Leiden University Medical Center
Leiden, , Netherlands
Site Status
NOT_YET_RECRUITING
Newcastle University
Newcastle upon Tyne, , United Kingdom
Site Status
NOT_YET_RECRUITING
Countries
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United States
Netherlands
United Kingdom
Central Contacts
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Facility Contacts
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References
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van de Velde NM, Hooijmans MT, Sardjoe Mishre ASD, Keene KR, Koeks Z, Veeger TTJ, Alleman I, van Zwet EW, Beenakker JM, Verschuuren JJGM, Kan HE, Niks EH. Selection Approach to Identify the Optimal Biomarker Using Quantitative Muscle MRI and Functional Assessments in Becker Muscular Dystrophy. Neurology. 2021 Aug 3;97(5):e513-e522. doi: 10.1212/WNL.0000000000012233. Epub 2021 Jun 23.
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Barp A, Laforet P, Bello L, Tasca G, Vissing J, Monforte M, Ricci E, Choumert A, Stojkovic T, Malfatti E, Pegoraro E, Semplicini C, Stramare R, Scheidegger O, Haberlova J, Straub V, Marini-Bettolo C, Lokken N, Diaz-Manera J, Urtizberea JA, Mercuri E, Kyncl M, Walter MC, Carlier RY. European muscle MRI study in limb girdle muscular dystrophy type R1/2A (LGMDR1/LGMD2A). J Neurol. 2020 Jan;267(1):45-56. doi: 10.1007/s00415-019-09539-y. Epub 2019 Sep 25.
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BACKGROUND
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Jaka O, Azpitarte M, Paisan-Ruiz C, Zulaika M, Casas-Fraile L, Sanz R, Trevisiol N, Levy N, Bartoli M, Krahn M, Lopez de Munain A, Saenz A. Entire CAPN3 gene deletion in a patient with limb-girdle muscular dystrophy type 2A. Muscle Nerve. 2014 Sep;50(3):448-53. doi: 10.1002/mus.24263. Epub 2014 Aug 5.
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Willis TA, Hollingsworth KG, Coombs A, Sveen ML, Andersen S, Stojkovic T, Eagle M, Mayhew A, de Sousa PL, Dewar L, Morrow JM, Sinclair CD, Thornton JS, Bushby K, Lochmuller H, Hanna MG, Hogrel JY, Carlier PG, Vissing J, Straub V. Quantitative magnetic resonance imaging in limb-girdle muscular dystrophy 2I: a multinational cross-sectional study. PLoS One. 2014 Feb 28;9(2):e90377. doi: 10.1371/journal.pone.0090377. eCollection 2014.
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Reyngoudt H, Marty B, Boisserie JM, Le Louer J, Koumako C, Baudin PY, Wong B, Stojkovic T, Behin A, Gidaro T, Allenbach Y, Benveniste O, Servais L, Carlier PG. Global versus individual muscle segmentation to assess quantitative MRI-based fat fraction changes in neuromuscular diseases. Eur Radiol. 2021 Jun;31(6):4264-4276. doi: 10.1007/s00330-020-07487-0. Epub 2020 Nov 21.
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Reference Type
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Other Identifiers
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Limb-Girdle Muscular Dystrophy
Identifier Type: OTHER
Identifier Source: secondary_id
GRASP-R1
Identifier Type: OTHER
Identifier Source: secondary_id
HM20025359
Identifier Type: -
Identifier Source: org_study_id
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