Non-invasive Evaluation of Urinary Titin as an IND-enabling Biomarker for Use in Duchenne Muscular Dystrophy (DMD) Clinical Trials
Children's Hospital of Philadelphia
Summary
A universal challenge in clinical investigation of novel therapeutics is the need for quantitative, objective biomarkers that directly address the mechanisms of disease and provide information relevant to clinically meaningful functional improvement. This has been a particular challenge in rare and slowly progressive diseases such as Duchenne Muscular Dystrophy (DMD). The investigators hypothesize that urinary N-terminal fragment of titin (NTFT) corresponding to activity level/intensity will define a high-precision, non-invasive biomarker of systemic muscle injury to enable serial measurements of efficacy and safety in the clinical investigation of gene therapy for DMD and other myopathies. This should provide a valuable exploratory, secondary and eventually primary outcome measure of therapeutic efficacy to minimize the enrollment size in informative early phase and pivotal clinical trials.
Description
The investigators are recruiting ambulatory individuals with Duchenne Muscular Dystrophy (DMD) or Becker Muscular Dystrophy (BMD), and healthy volunteers. At 3 regular clinical visits, participants will perform a descending stair walk down 2 flights of stairs. Urine will be collected before and after to measure how urinary N-terminal fragment of titin (NTFT) levels are impacted by the activity. Participants will also perform a standard battery of neuromuscular tests, including North Star Ambulatory Assessment and Timed Function Tests. These will be performed as part of the regular clinic visi…
Eligibility
- Age range
- 2–10 years
- Sex
- Male
- Healthy volunteers
- Yes
DMD/BMD Subject Inclusion/Exclusion Criteria Inclusion Criteria: 1. Ambulatory at screening 2. Genetically confirmed diagnosis of DMD/BMD 3. Parental/guardian permission (informed consent) for children. Child assent will also be obtained from patients ages 7 years old and older and deemed by the investigator to be neurodevelopmentally appropriate 4. Access to electricity and a freezer in the home, in order to utilize the provided device and store collected samples Exclusion Criteria: * Non-ambulatory at Screening, defined as unable to walk independently and needing assistive devices * Fema…
Interventions
- OtherDescending stair walk
Subjects will participate in a brief on-site, descending stair walk. Subjects will walk down stairs, up to a maximum 2 floors, under the supervision of a physical therapist or study team member.
Location
- Children's Hospital of PhiladelphiaPhiladelphia, Pennsylvania