Limb Girdle Muscular Dystrophy, Muscular Dystrophies
Conditions
Keywords
LGMD, Limb Girdle Muscular Dystrophy, CAPN3, ANO5, DYSF, DNAJB6, Sarcoglycan, SGCA, SGCB, SGCD, SGCG
Brief summary
Limb Girdle Muscular Dystrophy comprise a group of disorders made up of over 30 mutations which share a common phenotype of progressive weakness of the shoulder and hip girdle muscles. While the individual genetic mutations are rare, as a cohort, LGMDs are one of the four most common muscular dystrophies. The overall goal of project 1 is to define the key phenotypes as measured by standard clinical outcome assessments (COAs) for limb girdle muscular dystrophies (LGMD) to hasten therapeutic development.
Detailed description
The genetic heterogeneity has been a barrier to broad natural history efforts, with prior investigations often limited to single gene mutations. Much attention is paid to the variability within individual mutations (e.g. distal presentations), as opposed to defining the best strategy for measuring change in overall LGMD disease burden. This presents a major dilemma for LGMD rare disease research: how to balance diverse genes leading to overlapping phenotypes, versus variants in the same gene leading to divergent phenotypes. What is clear, is as a group, LGMDs are chronic and progressive leading to significant lifetime morbidity and represent a large unmet clinical need. Recent developments in the investigator's genetic understanding of LGMD and molecular approaches to therapy have led to proposed gene replacement therapies for at least three of the LGMD mutations. Several of these gene replacement therapies are currently in pre-clinical/phase 1 testing, leading to an urgent need for natural history data. In addition, non-specific therapies which target muscle mass or function are being tested in other muscular dystrophies and may prove beneficial for LGMD.
Interventions
None listed
Sponsors
Virginia Commonwealth University
Newcastle University
Nationwide Children's Hospital
Washington University School of Medicine
University of Iowa
University of Minnesota
University of California, Irvine
Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
University of Colorado, Denver
University of Kansas Medical Center
Study design
Observational model
COHORT
Time perspective
OTHER
Eligibility
Sex/Gender
ALL
Age
4 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
- Arm 1: * Age between 4-65 at enrollment * Clinically affected (defined as weakness on bedside evaluation in either a limb-girdle pattern, or in a distal extremity) * A genetically or functionally confirmed mutation in ANO5, CAPN3, DYSF, DNAJB6 or SGCA-G. * Willing and able to give informed consent and follow all study procedures and requirements Inclusion Criteria - Arm 2: * Age between 4-65 at enrollment * Clinically affected (defined as weakness on bedside evaluation in either a limb-girdle pattern, or in a distal extremity) * a genetically confirmed mutation in SGCA-G * Willing and able to give informed consent and follow all study procedures and requirements
Exclusion criteria
- Arm 1: * 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. * History of a bleeding disorder, platelet count \<50,000, current use of an anticoagulant. * Positive pregnancy test at time any timepoint during the trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in mobility | Baseline to 12 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. |
| Change in motor performance | Baseline to 12 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. |
| Change in upper limb function characteristics | Baseline to 12 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. |
| Change in Forced vital capacity (FVC) | Baseline to 12 months | Volume of air forcefully exhaled will be measured using Spirometry performed in a sitting position using standardized equipment |
| Changes in Forced expiratory volume (FEV1) | Baseline to 12 months | Volume of air forcefully exhaled in one second will be measured using Spirometry performed in a sitting position using standardized equipment |
| Change in activity limitations | Baseline to 12 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. |
| Change in self-reported physical health | Baseline to 12 months | PROMIS Physical Health is part of a set of patient-reported measures developed by a National Institute of Health that 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. |
| Change in overall health | Baseline to 12 months | Domain Delta Questionnaire is a patient reported measure that assesses overall health over the previous 12 months. |
Countries
United Kingdom, United States
Contacts
PRINCIPAL_INVESTIGATORNicholas Johnson, MD
Virginia Commonwealth University
Outcome results
None listed