Long-Term Development of Muscular Dystrophy Outcome Assessments

Study Overview
=================
Brief Summary
-----------------
This is a 24-month, observational study of up to 1000 participants with Limb Girdle Muscular Dystrophy (LGMD), Myotonic Dystrophy Type 2 (DM2), and late onset Pompe disease (LOPD).

Detailed Description
-----------------
Limb Girdle Muscular Dystrophy (LGMD) 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. Myotonic Dystrophy Type 2 (DM2) is a more recently discovered, rare type of myotonic dystrophy. DM2 is inherited in an autosomal dominant pattern and is caused by an unstable CCTG expansion. DM2 affects the muscles and other body systems (e.g. heart and eyes). Pompe disease is a rare, multisystemic, hereditary disease which is caused by pathogenic variations in the GAA gene. Late onset Pompe disease (LOPD) refers to cases in which hypertrophic cardiomyopathy did not manifest or was not diagnosed at or under the age of 1 year. LOPD is characterized by skeletal muscle weakness which causes mobility problems and impacts the respiratory system. The overall goal of this project is to extend prior observational studies conducted within the GRASP LGMD network to define the key phenotypes as measured by standard clinical outcome assessments (COAs) for multiple rare types of muscular dystrophy to hasten therapeutic development.

Official Title
-----------------
Long-Term Development of Muscular Dystrophy Outcome Assessments (GRASP-01-005)

Conditions
-----------------
LGMD2E, LGMD1B, LGMD1C, LGMD1D, LGMD1E, LGMD1F, LGMD1G, LGMD1H, LGMD2A, LGMD2B, LGMD2C, LGMD2D, LGMD2F, LGMD2G, LGMD2I, LGMD2J, LGMD2K, LGMD2L, LGMD2M, LGMD2N, LGMD2O, LGMD2P, LGMD2Q, LGMD2S, LGMD2T, LGMD2U, LGMD2W, LGMD2X, LGMD2Y

Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age between 6-50 years at enrollment Clinically affected (defined as weakness on bedside evaluation in a pattern consistent with proximal weakness) Genetic confirmation of a LGMD, DM2, or LOPD FVC above 30% of predicted Exclusion Criteria: 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 Participation in a clinical trial receiving an investigational product

Ages Eligible for Study
-----------------
Minimum Age: 6 Years
Maximum Age: 50 Years

Sexes Eligible for Study
-----------------
All

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| LGMD, DM2, LOPD<br> | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To explore the suitability and feasibility of the North Star Assessment for LGMD (NSAD) in the muscular dystrophies | The 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 adapted North Star Ambulatory Assessment and the Motor Function Measure 20 with a maximum score of 54. | Baseline to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To explore the utility of the 100 meter timed test as a clinical outcome assessment in the muscular dystrophies | The participant will be asked to complete 4 laps around 2 cones set 25 meters apart, as quickly and safely as possible, walking or running if able. The total time to complete the 4 laps is recorded in seconds. | Baseline to 24 months | 
| To explore the utility of the Performance of the Upper Limb 2.0 (PUL 2.0) assessment as a clinical outcome assessment in the muscular dystrophies | The PUL 2.0 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. | Baseline to 24 months | 
| To explore the utility of spirometry as a clinical outcome assessment in the muscular dystrophies | Spirometry is a breathing assessment comprised of: seated and supine forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), and slow vital capacity (SVC). This assessment is performed using standardized equipment. | Baseline to 24 months | 
| To explore the utility of the LGMD-HI questionnaire as a patient-reported outcome measure in the muscular dystrophies. | The LGMD Health Index (LGMD-HI) is a disease-specific, patient-reported measure that assesses overall health-related quality of life in LGMD. | Baseline to 24 months | 
| To explore the utility of the PROMIS-57 as a patient-reported outcome measure in the muscular dystrophies. | The PROMIS-57 is a set of patient-reported measures developed by the NIH. The social health set of questions evaluates general social health by assessing ability to participate in social roles and activities, companionship, satisfaction with social roles and activities, social isolation, and social support. The mental health set evaluates general mental health by assessing anxiety, depression, alcohol use, anger, cognitive function, life satisfaction, meaning and purpose, positive affect, psychosocial illness impact, self-efficacy for managing chronic conditions, smoking, and substance use. The physical health set 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. | Baseline to 24 months | 
| To explore the utility of the Domain Delta as a patient-reported outcome measure in the muscular dystrophies | The Domain Delta questionnaire is a patient-reported outcome measure that assesses overall health over the previous 12 months. | Baseline to 24 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Muscular Dystrophy, Myotonic Dystrophy, Limb Girdle Muscular Dystrophy, LGMD, LOPD, Late Onset Pompe Disease