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.
Study Type
OBSERVATIONAL
Enrollment
101
University of California Irvine
Irvine, California, United States
University of Colorado Anschutz Medical Campus
Aurora, Colorado, United States
University of Florida
Gainesville, Florida, United States
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: * Cohort A: completes the 10 MWT unaided in ≥ 4 to ≤ 12 seconds * Cohort B: completes the walk unaided in \> 12 seconds or is non-ambulatory
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Through study completion at 12 months
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University of Iowa
Iowa City, Iowa, United States
University of Kansas Medical Center
Kansas City, Kansas, United States
Kennedy Krieger Institute
Baltimore, Maryland, United States
Washington University School of Medicine
St Louis, Missouri, United States
Atrium Health
Charlotte, North Carolina, United States
Nationwide Children's Hospital
Columbus, Ohio, United States
Virginia Commonwealth University
Richmond, Virginia, United States
...and 1 more locations
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Through study completion at 12 months
To develop clinical outcome assessments for LGMD2i
To determine the sensitivity of the COAs to longitudinal disease progression
Time frame: Through study completion at 12 months