Defining Endpoints in Becker Muscular Dystrophy (GRASP-01-002)

This is a 24-month, observational study of 50 participants with Becker muscular dystrophy (BMD)

Study Overview

• Status: Active, not recruiting
• Conditions: Muscular Dystrophies; Becker Muscular Dystrophy; Muscular Dystrophy in Children; Muscular Dystrophy, Becker

Detailed Description

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.

• Study Type: Observational
• Enrollment (Estimated): 80

Contacts and Locations

Study Locations

• New Zealand
  • Auckland, New Zealand
    • University of Auckland
• United Kingdom
  • Newcastle upon Tyne, United Kingdom, NE1 4EP
    • John Walton Muscular Dystrophy Research Centre
• United States
  • California
    • Orange, California, United States, 92868
      • University of California, Irvine
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Anschutz Medical Campus
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Kennedy Krieger Institute
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • Ohio
    • Columbus, Ohio, United States, 43205
      • Nationwide Children's Hospital
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Individuals age 6+ who are clinically affected with Becker Muscular Dystrophy

Description

Inclusion Criteria:

For ages 6-12

1. Clinically affected (defined as weakness on bedside evaluation in a pattern consistent with BMD)
2. Genetic confirmation of an in-frame dystrophin mutation
3. Ambulatory
4. Willing and able to give informed consent and follow all procedures and requirements

For ages 13 and older

1. Clinically affected (defined as weakness on bedside evaluation in a pattern consistent with BMD)
2. Genetic confirmation of a dystrophin mutation
3. 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

1. Out of frame dystrophin mutation
2. Use of chronic corticosteroids at baseline, defined as greater than 6 months of chronic use, will be limited to 20% of the overall population
3. Non-ambulatory, defined as the inability to walk 10 meters without assistive device (excluding orthotics)
4. >16 hours of ventilatory support
5. 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.
6. Under the age of 6 at time of enrollment
7. 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

1. Loss of ambulation prior to age 16
2. Use of chronic corticosteroids, defined as greater than 6 months of chronic use, will be limited to 20% of the overall population
3. Less than 30% of the overall population will be non-ambulatory, defined as the inability to walk 10 meters without assistive device (excluding orthotics)
4. >16 hours of ventilatory support
5. Subjects aged 13-16 only: time to rise >10 seconds
6. For MR Cohort: Have contraindications to MRI or MRS (e.g., non-MR compatible implanted medical devices or severe claustrophobia)

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Other

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the natural history of MR measures of muscle quality in BMD	MAGNETIC RESONANCE IMAGING FAT FRACTION: This assessment measures fat fraction using chemical shift-based, often called Dixon, imaging and will be performed in axial plane at the thigh and lower leg.	Through study completion, an average of 2 years
MAGNETIC RESONANCE IMAGING TRANSVERSE RELAXATION TIME (T2)	This assessment measures muscle quality using T2 weighted imaging and will be performed in axial plane at the thigh and lower leg.	Through study completion, an average of 2 years
MAGNETIC RESONANCE SPECTROSCOPY TRANSVERSE RELAXATION TIME (T2)	Single voxel multiecho magnetic resonance spectra will be acquired for the calculation of water transverse relaxation time.	Through study completion, an average of 2 years
Biomarker Assessment - Blood Sampling	A blood sample will be collected at the baseline visit to obtain DNA samples for biomarker discovery. Serum will be collected at each in-person visit for other exploratory biomarkers. These samples will be stored in the biorepository, and provide the foundation for future pilot projects, and serve as a resource to the greater BMD community.	Through study completion, an average of 2 years

Collaborators and Investigators

• Sponsor: Virginia Commonwealth University
• Collaborators: Edgewise Therapeutics, Inc.
• Investigators: Principal Investigator: Nicholas E. Johnson, MD, Virginia Commonwealth University

Publications and helpful links

General Publications

• Straub V, Guglieri M. An update on Becker muscular dystrophy. Curr Opin Neurol. 2023 Oct 1;36(5):450-454. doi: 10.1097/WCO.0000000000001191. Epub 2023 Aug 21.

Study record dates

Study Major Dates

• Study Start (Actual): April 13, 2022
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026

Study Registration Dates

• First Submitted: January 25, 2022
• First Submitted That Met QC Criteria: February 15, 2022
• First Posted (Actual): February 25, 2022

Study Record Updates

• Last Update Posted (Actual): June 10, 2026
• Last Update Submitted That Met QC Criteria: June 8, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: BMD; Becker Muscular Dystrophy; Clinical research; Edgewise Therapeutics
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Nervous System Diseases; Muscular Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Muscular Disorders, Atrophic; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Muscular Dystrophies; Muscular Dystrophy, Duchenne
• Other Study ID Numbers: HM20023412; GRASP-BMD (Other Identifier: Virginia Commonwealth University)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No