Urinary Titin Biomarker in DMD

N/ARecruitingNCT07332013

Children's Hospital of Philadelphia50 enrolled

Overview

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.

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 visit. Participants will wear an activity monitor during all tests. After both the first and second visits, participants will be sent home with an activity monitor to measure the participants activity over the course of 7 days. The participant's urine will be collected and frozen 3 times a day (morning, afternoon, and evening) during this period. The investigators will correlate physical activity intensity with the urinary NTFT (titin) levels and the severity of the disease (which will be based on the results of clinical neuromuscular tests). If there is a clinically-indicated blood draw, participants will have the option to allow collection of an additional sample for exploratory analysis of additional biomarkers.

Study Type

INTERVENTIONAL

Allocation

Purpose

Eligibility

Sex: MALEMin age: 2 YearsMax age: 10 YearsHealthy volunteers:

Medical Language ↔ Plain English

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 * Female patients * Parental/guardian unable to provide informed consent Healthy Control Subject Inclusion/Exclusion Criteria Inclusion criteria: 1. Healthy children without DMD, BMD, or other significant chronic medical disease 2. Ambulatory at Screening, defined as able to walk independently without assistive devices 3. Parental/guardian permission (informed consent). Child assent will also be obtained from patients aged 7 years 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 * Female patients * Parental/guardian unable to provide informed consent

Outcomes

Primary Outcomes

Change in urinary NTFT (titin) after structured activity

Change in urinary NTFT concentration will be measured before and after clinical visits, during which subjects will complete standard of care physical therapy assessments and perform a two-flight stair descent (if able).

Time frame: Day 1, 6-12 months , 12-18 months

Urinary NTFT (titin) relative during unstructured activity in home environment

Change in urinary NTFT (titin) concentration over 1 week in response to unstructured activity at home and will be measured after each scheduled visit. This period of home NTFT monitoring will occur at the same time as activity monitoring described in outcome measure #3.

Time frame: Day 1, 6-12 months, 12- 18 months

Unstructured activity level as assessed by wearable activity device

Subjects' daily movement and activity levels will be measured continuously over 1 week at home using a pair of wearable accelerometry sensors. This will be completed after each scheduled clinical visit. This period of home activity monitoring will occur in conjunction with NTFT monitoring as described in outcome measure #2.