Urinary Titin Biomarker for Duchenne Muscular Dystrophy

Overseen By Julianne Larosa, MPH

Age: < 18

Sex: Male

Trial Phase: Academic

Sponsor: Children's Hospital of Philadelphia

Disqualifiers: Non-ambulatory, Female, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to measure muscle damage in individuals with Duchenne Muscular Dystrophy (DMD) using a urine test. Researchers aim to determine if a specific protein fragment in urine, the N-terminal fragment of titin (NTFT), can reliably track the progression and treatment effects of DMD. They seek boys who can walk independently, have a confirmed genetic diagnosis of DMD or Becker Muscular Dystrophy (BMD), and have access to electricity and a freezer at home for sample storage. As an unphased trial, this study offers participants the chance to contribute to groundbreaking research that could improve the monitoring and treatment of DMD.

What prior data suggests that this biomarker is safe for use in clinical trials?

Research has shown that a protein segment called NTFT can aid in studying Duchenne Muscular Dystrophy (DMD). Changes in NTFT levels can indicate muscle injury and relate to a protein called microdystrophin, which plays a crucial role in DMD.

NTFT is measured in urine, providing a simple method to check for muscle damage without needles or blood samples. When muscles sustain damage, NTFT levels in urine rise, confirming its usefulness in monitoring muscle health.

In terms of safety, NTFT serves as a tool to assess muscle condition, not as a medication, so it lacks the side effects drugs might have. Studies have not reported any safety concerns with using NTFT to track muscle injury, suggesting it is safe to use as a biomarker. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the N-terminal fragment of titin (NTFT) for Duchenne Muscular Dystrophy (DMD) because it introduces a new approach to monitoring the disease. Unlike traditional treatments that focus on managing symptoms or slowing progression, NTFT is a biomarker that may allow for earlier detection and better tracking of the disease's progression through urine tests. This non-invasive method could lead to more timely and personalized treatment adjustments, potentially improving the quality of life for patients with DMD.

What evidence suggests that this biomarker is effective for Duchenne Muscular Dystrophy?

Research shows that a protein segment called NTFT might serve as a useful marker for Duchenne Muscular Dystrophy (DMD). Studies have found that changes in NTFT levels relate to microdystrophin, a protein that maintains muscle health in individuals with DMD. Early results suggest that measuring NTFT levels in urine could offer a more sensitive test than common methods like measuring the protein CK in blood. This indicates that NTFT could monitor treatment effectiveness in a simple, non-invasive manner through urine testing. Overall, NTFT has the potential to provide crucial information for evaluating new DMD treatments. ^{2 3 6 7 8}

Who Is on the Research Team?

Sabrina Yum, MD

Principal Investigator

Children's Hospital of Philadelphia

Benjamin Kozyak, MD

Principal Investigator

Children's Hospital of Philadelphia

Are You a Good Fit for This Trial?

This trial is for boys with Duchenne or Becker's Muscular Dystrophy who can walk and have a confirmed genetic diagnosis. They need access to electricity and a freezer at home. Healthy boys without these diseases or other chronic conditions, who can also walk independently, may participate as controls.

Inclusion Criteria

DMD/BMD Subject: Parental/guardian permission for children. Child assent for patients ages 7 years old and older

DMD/BMD Subject: Access to electricity and a freezer in the home, in order to utilize the provided device and store collected samples

Healthy Control Subject: Parental/guardian permission. Child assent for patients aged 7 years and older

Exclusion Criteria

I am a female patient with DMD/BMD.

DMD/BMD Subject: Parental/guardian unable to provide informed consent

Healthy Control Subject: Parental/guardian unable to provide informed consent

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Clinical Visits

Participants attend 3 regular clinical visits for neuromuscular tests and urine collection

6-18 months

3 visits (in-person)

Home Monitoring

Participants wear an activity monitor and collect urine samples at home over 1 week after each clinical visit

1 week per visit

Follow-up

Participants are monitored for changes in neuromuscular performance and urinary NTFT levels over time

12-18 months

What Are the Treatments Tested in This Trial?

Interventions

• N-terminal fragment of titin (NTFT)

Trial Overview

The trial is testing if the levels of a muscle injury biomarker in urine, called NTFT, change after doing activities like descending stairs. This could help measure how well new treatments for muscular dystrophy are working without invasive procedures.

How Is the Trial Designed?

Group I: Experimental Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Children's Hospital of Philadelphia

Lead Sponsor

Trials

749

Recruited

11,400,000+

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT07332013

NCT07332013 | Urinary Titin Biomarker in DMD

Urine will be collected before and after to measure how urinary N-terminal fragment of titin (NTFT) levels are impacted by the activity.

2.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/38229112/

N-terminal titin fragment: a non-invasive ...

Changes in the N-terminal fragment of titin, a well-known, previously characterized biomarker of DMD, were correlated with the expression of microdystrophin ...

3.

nature.com

nature.com/articles/s41598-025-85369-5

Titin fragment is a sensitive biomarker in Duchenne ...

These results suggest that urine/plasma titin fragment levels could be a more sensitive biomarker than plasma CK activity.

4.

link.springer.com

link.springer.com/article/10.1186/s13395-023-00334-y

N-terminal titin fragment: a non-invasive, pharmacodynamic ...

Multiple clinical trials to assess the efficacy of AAV-directed gene transfer in participants with Duchenne muscular dystrophy (DMD) are ongoing ...

5.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0009898117304679

Diagnostic and clinical significance of the titin fragment in ...

The N-terminal fragment of titin in urine has potential as a diagnostic and clinical biomarker for DMD. Introduction. Duchenne muscular dystrophy (DMD) (OMIM# ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10790446/

N-terminal titin fragment: a non-invasive, ...

Changes in the N-terminal fragment of titin, a well-known, previously characterized biomarker of DMD, were correlated with the expression of microdystrophin ...

7.

sciencedirect.com

sciencedirect.com/science/article/pii/S0960896617300263

Dramatic elevation in urinary amino terminal titin fragment ...

These results suggest that urinary N-ter titin is present at low basal concentrations in normal urine and increases dramatically coincident with muscle damage ...

8.

journals.plos.org

journals.plos.org/plosone/article?id=10.1371/journal.pone.0289185

Urinary titin is not an early biomarker of skeletal muscle ...

In this study, we hypothesized that urinary N-titin would be a potential early biomarker of skeletal muscle atrophy in mice caused by sciatic nerve denervation.