Urinary Titin Biomarker in DMD

Non-invasive Evaluation of Urinary Titin as an IND-enabling Biomarker for Use in Duchenne Muscular Dystrophy (DMD) Clinical Trials

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.

Study Overview

• Status: Recruiting
• Conditions: Duchenne Muscular Dystrophy (DMD); Becker's Muscular Dystrophy (BMD)
• Intervention / Treatment: Other: Descending stair walk

Detailed 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 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
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Calliope O'Donnell, MS; Phone Number: 267-426-7786; Email: odonnellcs@chop.edu
• Study Contact Backup: Name: Julianne Larosa, MPH; Phone Number: 267-426-7875; Email: Larosaj1@chop.edu

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • Children's Hospital of Philadelphia
      • Contact: Calliope O'Donnell, MS; Phone Number: 267-426-7786; Email: odonnellcs@chop.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental	Other: Descending 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	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.	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.	Day 1, 6-12 months, 12-18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in neuromuscular performance over time, as assessed by routine North Star Ambulatory Assessment (NSAA)	North Star Ambulatory Assessment is a standardized set of 17 different activities such as standing, sitting, climbing up and down one step, getting up from the floor, walking, and balancing, which will measure the subjects' motor function while the PT assesses their performance. NSAA will be evaluated at each scheduled visit. The change over time will be evaluated.	Day 1, 6-12 months, 12-18 months
Neuromuscular performance over time, as assessed by time to rise from floor (TTR).	The time it takes the participant to get up from the floor will be evaluated at each scheduled visit. The change in TTR over time will be evaluated.	Day 1, 6-12 months, and 12-18 months
Neuromuscular performance over time, as assessed by 4 stair climb (4SC).	The time it takes the participant to climb 4 stairs will be evaluated at each scheduled visit. The change in 4SC over time will be evaluated.	Day 1, 6-12 months, 12-18 months
Neuromuscular performance over time, as assessed by 10 meter walk (10MW)	The time it takes the participant to walk 10 meters will be evaluated at each scheduled visit. The change in 10MW time over time will be evaluated.	Day 1, 6-12 months, 12-18 months
Types of activities	Subject's will record type of activity and time spent doing activities in an activity log. The amount of time spent doing activities involving walking and running will be quantified for each study group during 1 week at home following each scheduled visit.	Day 1, 6-12 months, 12-18 months

Collaborators and Investigators

• Sponsor: Children's Hospital of Philadelphia
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS)
• Investigators: Principal Investigator: Sabrina Yum, MD, Children's Hospital of Philadelphia; Principal Investigator: Benjamin Kozyak, MD, Children's Hospital of Philadelphia

Study record dates

Study Major Dates

• Study Start (Actual): March 4, 2026
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2029

Study Registration Dates

• First Submitted: November 6, 2025
• First Submitted That Met QC Criteria: January 9, 2026
• First Posted (Actual): January 12, 2026

Study Record Updates

• Last Update Posted (Actual): April 8, 2026
• Last Update Submitted That Met QC Criteria: April 7, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Nervous System Diseases; Muscular Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Muscular Disorders, Atrophic; Muscular Dystrophies; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Muscular Dystrophy, Duchenne
• Other Study ID Numbers: 23-021450; U01NS134672 (U.S. NIH Grant/Contract)

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