Defining Endpoints in Becker Muscular Dystrophy

Muscular Dystrophies Clinical Trial

— GRASP-01-002  

Official title:

Defining Endpoints in Becker Muscular Dystrophy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05257473
• Other study ID #: HM20023412
• Secondary ID: GRASP-BMD
• Status: Recruiting
• Start date: April 13, 2022
• Est. completion date: May 2026

Study information

• Verified date: April 2024
• Source: Virginia Commonwealth University
• Contact: Ruby Langeslay
• Phone: 804-828-8481
• Email: ruby.langeslay[@]vcuhealth.org
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: May 2026
• Est. primary completion date: May 2025
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 6 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Becker Muscular Dystrophy
• Muscular Dystrophies
• Muscular Dystrophy, Becker
• Muscular Dystrophy, Duchenne

Locations

Country	Name	City	State
New Zealand	University of Auckland	Auckland
United Kingdom	John Walton Muscular Dystrophy Research Centre	Newcastle Upon Tyne
United States	University of Colorado Anschutz Medical Campus	Aurora	Colorado
United States	Kennedy Krieger Institute	Baltimore	Maryland
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	University of Iowa	Iowa City	Iowa
United States	Kansas University Medical Center	Kansas City	Kansas
United States	University of Minnesota	Minneapolis	Minnesota
United States	University of California, Irvine	Orange	California
United States	Virginia Commonwealth University	Richmond	Virginia
United States	Washington University School of Medicine	Saint Louis	Missouri

Sponsors (2)

Lead Sponsor	Collaborator
Virginia Commonwealth University	Edgewise Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  New Zealand,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Other	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
Other	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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