Clinical trial NCT05257473: Defining Endpoints in Becker Muscular Dystrophy
Official title: Defining Endpoints in Becker Muscular Dystrophy
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Becker Muscular Dystrophy
Muscular Dystrophies
Muscular Dystrophy in Children
Muscular Dystrophy, Becker
Keywords: Clinical research
BMD
Becker Muscular Dystrophy
Edgewise Therapeutics
Lead sponsor: Virginia Commonwealth University
Sponsor class: OTHER
Collaborators: name: Edgewise Therapeutics, Inc.
First posted: 2022-02-25
Enrollment: 80
Sex: MALE
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: OTHER
Sampling method: PROBABILITY_SAMPLE
Study population: Individuals age 6+ who are clinically affected with Becker Muscular Dystrophy

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

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.

Eligibility criteria: 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)

Primary outcomes:
measure: To assess the natural history of measures of muscle function in BMD
timeFrame: Through study completion, an average of 2 years
measure: 4-Stair Climb
timeFrame: Through study completion, an average of 2 years
measure: 100-Meter Timed Test
timeFrame: Through study completion, an average of 2 years
measure: PERFORMANCE OF UPPER LIMB 2.0 (PUL)
timeFrame: Through study completion, an average of 2 years
measure: HAND HELD DYNAMOMETRY (HHD) AND GRIP
timeFrame: Through study completion, an average of 2 years
measure: TIMED UP-AND-GO (TUG)
timeFrame: Through study completion, an average of 2 years
measure: Measures of Pulmonary Function (Seated and supine FVC)
timeFrame: Through study completion, an average of 2 years
measure: Measures of Pulmonary Function (MEP and MIP)
timeFrame: Through study completion, an average of 2 years
measure: Measures of Pulmonary Function (other)
timeFrame: Through study completion, an average of 2 years
measure: Measure of ejection fraction (ECHO)
timeFrame: Through study completion, an average of 2 years
measure: Measure of systolic and diastolic function (ECHO)
timeFrame: Through study completion, an average of 2 years
Secondary outcomes:
Other outcomes:
measure: To assess the natural history of MR measures of muscle quality in BMD
timeFrame: Through study completion, an average of 2 years
measure: MAGNETIC RESONANCE IMAGING TRANSVERSE RELAXATION TIME (T2)
timeFrame: Through study completion, an average of 2 years
measure: MAGNETIC RESONANCE SPECTROSCOPY TRANSVERSE RELAXATION TIME (T2)
timeFrame: Through study completion, an average of 2 years
measure: Biomarker Assessment - Blood Sampling
timeFrame: Through study completion, an average of 2 years
Locations:
city: Orange
country: United States
facility: University of California, Irvine
state: California
city: Aurora
country: United States
facility: University of Colorado Anschutz Medical Campus
state: Colorado
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Baltimore
country: United States
facility: Kennedy Krieger Institute
state: Maryland
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Auckland
country: New Zealand
facility: University of Auckland
city: Newcastle Upon Tyne
country: United Kingdom
facility: John Walton Muscular Dystrophy Research Centre
Study officials:
affiliation: Virginia Commonwealth University
name: Nicholas E. Johnson, MD
role: PRINCIPAL_INVESTIGATOR
References: