Defining Endpoints in Becker Muscular Dystrophy

Study Overview
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Brief Summary
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This is a 24-month, observational study of 80 participants with Becker muscular dystrophy (BMD)

Detailed Description
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Becker Muscular Dystrophy (BMD) is most frequently due to in-frame mutations in the dystrophin gene that are associated with reduced levels of frequently shortened dystrophin, though other mutations may be related to the Becker phenotype. There is wide variation in the age of onset and degree of progression, ranging from childhood to late adulthood. The more severe form of dystrophinopathy, Duchenne muscular dystrophy, has a more characteristic rate of progression and overall natural history. The wide variation in severity of progression has led to challenges in the design and conduct of approaching therapeutic trials. There is a need for a more rigorous natural history study to assist in the design of these promising therapeutic trials.

Official Title
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Defining Endpoints in Becker Muscular Dystrophy

Conditions
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Becker Muscular Dystrophy, Muscular Dystrophies, Muscular Dystrophy in Children, Muscular Dystrophy, Becker

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For ages 6-12 Clinically affected (defined as weakness on bedside evaluation in a pattern consistent with BMD) Genetic confirmation of an in-frame dystrophin mutation Ambulatory Willing and able to give informed consent and follow all procedures and requirements For ages 13 and older Clinically affected (defined as weakness on bedside evaluation in a pattern consistent with BMD) Genetic confirmation of a dystrophin mutation Willing and able to give informed consent and follow all procedures and requirements For participants in the MRI substudy: 1. Ambulatory, defined as able to walk 10 meters without assistive devices (orthotics allowed) Exclusion Criteria: For ages 6-12 Out of frame dystrophin mutation Use of chronic corticosteroids at baseline, defined as greater than 6 months of chronic use, will be limited to 20% of the overall population Non-ambulatory, defined as the inability to walk 10 meters without assistive device (excluding orthotics) >16 hours of ventilatory support 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. Under the age of 6 at time of enrollment For MR Cohort: Have contraindications to MRI or MRS (e.g., non-MR compatible implanted medical devices or severe claustrophobia) For ages 13 and older Loss of ambulation prior to age 16 Use of chronic corticosteroids, defined as greater than 6 months of chronic use, will be limited to 20% of the overall population Less than 30% of the overall population will be non-ambulatory, defined as the inability to walk 10 meters without assistive device (excluding orthotics) >16 hours of ventilatory support Subjects aged 13-16 only: time to rise >10 seconds For MR Cohort: Have contraindications to MRI or MRS (e.g., non-MR compatible implanted medical devices or severe claustrophobia)

Ages Eligible for Study
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Minimum Age: 6 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the natural history of measures of muscle function in BMD | North Star Assessment for LGMD (NSAD: The NSAD is a functional scale specifically designed to measure motor performance in individuals with LGMD and is being evaluated in BMD due to the similar limb-girdle pattern of weakness. 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 and higher scores indicate higher functional abilities. | Through study completion, an average of 2 years | 
| 4-Stair Climb | Participants will perform the 4-stair climb with instructions to ascend 4 steps as quickly and as safely possible, using handrails if needed. | Through study completion, an average of 2 years | 
| 100-Meter Timed Test | The participant will be asked to complete 4 laps around 2 cones set 25 meters apart as quickly as safely possible, running if able and the time in seconds is recorded. | Through study completion, an average of 2 years | 
| PERFORMANCE OF UPPER LIMB 2.0 (PUL) | The PUL is a tool designed for assessing upper limb function in persons with neuromuscular disorders. | Through study completion, an average of 2 years | 
| HAND HELD DYNAMOMETRY (HHD) AND GRIP | Hand held dynamometry 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. CITEC myometer will be used to measure the and Grip of the subject. These pinch and grip techniques will also capture the maximum strength in newtons for the muscle groups involved. | Through study completion, an average of 2 years | 
| TIMED UP-AND-GO (TUG) | The TUG will be administered using the appropriate stable seating surface (i.e., cube chair or straight back chair) to achieve 90 degree of both hip and knee flexion when participant is seated with both feet flat on the floor to start. The test should be performed barefoot. The fastest time to stand from the chair, walk 3 meters, and return to seated, will be recorded. | Through study completion, an average of 2 years | 
| Measures of Pulmonary Function (Seated and supine FVC) | Spirometry will be performed in a sitting and supine position using standardized equipment. Forced vital capacity (FVC) sitting and supine. | Through study completion, an average of 2 years | 
| Measures of Pulmonary Function (MEP and MIP) | Sitting maximal expiratory and inspiratory pressures (MEP and MIP) will be assessed. | Through study completion, an average of 2 years | 
| Measures of Pulmonary Function (other) | Use of nocturnal or daytime positive pressure ventilation (PPV) (e.g., BiPAP or CPAP) will be recorded. | Through study completion, an average of 2 years | 
| Measure of ejection fraction (ECHO) | A transthoracic echocardiogram (ECHO) will be performed. Measures of ejection fraction will be recorded. | Through study completion, an average of 2 years | 
| Measure of systolic and diastolic function (ECHO) | A transthoracic echocardiogram (ECHO) will be performed. Measures of presence of systolic and diastolic function will be recorded. | Through study completion, an average of 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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BMD, Clinical research, Becker Muscular Dystrophy, Edgewise Therapeutics