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| Name | Class |
|---|---|
| Virginia Commonwealth University | OTHER |
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The overall goal of this natural history study is to define the key LGMD2i phenotypes as measured by standard clinical outcome assessments (COAs), and to validate a muscle biomarker for LGMD2i to support therapeutic development.
Limb Girdle Muscular Dystrophy (LGMD) 2i is an autosomal recessive form of LGMD that is due to missense mutations in the Fukutin-related protein (FKRP) gene. Patients develop progressive proximal muscle weakness that leads to loss of ambulation. Patients will also commonly develop a cardiomyopathy and respiratory compromise.
There are promising new therapies that have been developed and as a result therapeutic trials are approaching.
The rationale for this study is to define appropriate COAs for LGMD2i, which will facilitate therapeutic development and ensure properly powered clinical trials. In addition, measurement of dystroglycan in muscles represents a potential muscle biomarker that could be used in early phase clinical trials as a measure of target engagement. The clinical utility of changes in dystroglycan has not been validated in human samples.
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| Measure | Description | Time Frame |
|---|---|---|
| 10-Meter walk (10 MWT) -mobility | The 10 MWT will be used to determine the ambulatory Cohort for of all subjects. For the purposes of this study, the definitions for ambulation are as follows:
| Through study completion at 12 months |
| 100-Meter Timed Test (100m) - mobility | The 100m timed test is designed to capture maximal ambulatory capacity. The participant will be asked to complete 4 full laps around 2 cones set 25 meters apart as quickly and as safely as possible, including running if able. This will not be assessed in participants with a 10-meter walk time greater than 12 seconds. | Through study completion at 12 months |
| NSAD- Motor performance | 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. | Through study completion at 12 months |
| Timed up-and-go (TUG) - mobility | The TUG is an assessment used to evaluate functional ambulation, balance, and fall risk. The fastest time to rise from a chair, walk 3 meters, and return to sitting independently without an assistive device will be recorded. This will not be assessed in Cohort B participants. | Through study completion at 12 months |
| FVC - Pulmonary function | The total amount of air exhaled during the forced expiratory volume test (Forced vital capacity - FVC) will be assessed in a sitting position only. |
| Measure | Description | Time Frame |
|---|---|---|
| To develop clinical outcome assessments for LGMD2i | To determine the sensitivity of the COAs to longitudinal disease progression | Through study completion at 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| To validate potential biomarkers | To develop a reliable measure of dystroglycosylation in human skeletal muscle by using fresh tissue biopsy. A muscle biopsy will be collected at baseline and 6 months from the right tibialis anterior. The biopsy site will be uniform between investigators. The investigators will utilize a 14-gauge Supercore biopsy instrument to take a total of three aspirations from the same site. |
Inclusion Criteria:
Exclusion Criteria:
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Study participants will be identified through self-selection and direct recruitment options. Participants will be identified from the population of individuals who are followed at the neuromuscular clinics. Participants will also be solicited from the Global FKRP registry.
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| Name | Affiliation | Role |
|---|---|---|
| Nicholas E Johnson, MD | Virginia Commonwealth University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of California Irvine | Irvine | California | 92697 | United States | ||
| University of Colorado Anschutz Medical Campus |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41938495 | Derived | Vissing J, Mozaffar T, Johnson NE, Mathews KD, Wicklund MP, Weihl C, Leung DG, Statland JM, Kang PB, Zingariello CD, Lowes LP, Desai U, Bates K, Alfano LN, Xie H, St Romain J, Blankenbiller T, McLendon G, Rajasingham T, Heitzer M, Wu-Zhang AX, Tripp K, Rodriguez HM, Sproule D; as the GRASP-LGMD Consortium. Quantitative Measurement of Glycosylated ⍺-Dystroglycan as a Biomarker for Disease Severity in Limb-Girdle Muscular Dystrophy Type 2I/R9. Neurol Genet. 2026 Apr 1;12(2):e200370. doi: 10.1212/NXG.0000000000200370. eCollection 2026 Apr. |
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| ID | Term |
|---|---|
| D009136 | Muscular Dystrophies |
| D049288 | Muscular Dystrophies, Limb-Girdle |
| C564612 | Muscular Dystrophy, Limb-Girdle, Type 2I |
| ID | Term |
|---|---|
| D020966 | Muscular Disorders, Atrophic |
| D009135 | Muscular Diseases |
| D009140 | Musculoskeletal Diseases |
| D009468 | Neuromuscular Diseases |
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Blood and Tissue samples will be taken for biomarker development and retained for future research. No clinical diagnosis will be given to patients.
| Through study completion at 12 months |
| Timed 4 stair Climb (4SC) - mobility | The 4SC quantifies the time required for the participant to ascend 4 standard steps. This will not be assessed in participants with a 10 meter walk time greater than 12 seconds. | Through study completion at 12 months |
| 9 Hole Peg Test (9HPT) - distal upper extremity function | The 9HPT is a quantitative measure of distal upper extremity function. It measures the time required for patients to place 9 pegs in the 9 holes on the board and then remove them as quickly as possible. | Through study completion at 12 months |
| Performance of Upper Limb (PUL 2.0) - limb function | The PUL is a tool designed for assessing upper limb function in persons with neuromuscular disorders. It was developed as a conceptual framework reflecting the progression of weakness and natural history of functional decline in Duchenne muscular dystrophy (DMD). There are 22 scored items; a score of 42 indicates the highest level of independent function and 0 the lowest. | Through study completion at 12 months |
| Hand Held Dynamometry (HHD) - isometric strength | HHD using the MicroFET2 myometer will be utilized to capture isometric strength in target muscle groups. Maximum strength in kilograms will be reported for each muscle group provided a continuous scale variable for analysis. | Through study completion at 12 months |
| Baseline, Month 6 |
| To understand the change from baseline in muscle mass using Magnetic Resonance Imaging | To understand the change from baseline in muscle mass using Magnetic Resonance Imaging | Baseline, Month 6, Month 12 |
| Aurora |
| Colorado |
| 80045 |
| United States |
| University of Florida | Gainesville | Florida | 32610 | United States |
| University of Iowa | Iowa City | Iowa | 52242 | United States |
| University of Kansas Medical Center | Kansas City | Kansas | 66160 | United States |
| Kennedy Krieger Institute | Baltimore | Maryland | 21205 | United States |
| Washington University School of Medicine | St Louis | Missouri | 63110 | United States |
| Atrium Health | Charlotte | North Carolina | 28207 | United States |
| Nationwide Children's Hospital | Columbus | Ohio | 43205 | United States |
| Virginia Commonwealth University | Richmond | Virginia | 23298 | United States |
| Copenhagen Neuromuscular Center | Copenhagen | Denmark |
| D009422 | Nervous System Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |