Identifying biomarkers and clinical endpoints in Myotonic Dystrophy Type 1

Establishing Biomarkers and Clinical Endpoints in Myotonic Dystrophy Type 1 (END-DM1)

This study is trying to learn more about Myotonic Dystrophy Type 1 by looking at how the disease affects around 700 adults over two years, including their muscle health and daily activities.

Quick facts

• Study type: Observational
• Enrollment: 700 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Virginia Commonwealth University (Academic / other)
• Locations: 17 sites (La Jolla, California and 16 other locations)
• Trial ID: NCT03981575 on ClinicalTrials.gov

What this trial studies

This observational study aims to enhance the understanding of Myotonic Dystrophy Type 1 (DM1) by addressing gaps in data regarding its natural history and biomarkers. Approximately 700 adult participants will be enrolled across 15 centers, where they will undergo standard care and participate in assessments at baseline, 12 months, and 24 months. The study includes sub-studies focusing on muscle biopsies, COVID-19 responses, and daily physical activity to capture the full spectrum of disease severity and patient experiences. The goal is to refine sample collection and analysis procedures to better manage patient heterogeneity in DM1.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 70 with a clinical diagnosis of Myotonic Dystrophy Type 1.

Not a fit: Patients with symptomatic renal or liver disease, uncontrolled diabetes, or those currently participating in another clinical trial may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved diagnostic and monitoring strategies for patients with Myotonic Dystrophy Type 1.

How similar studies have performed: Previous studies have shown promise in understanding Myotonic Dystrophy, but this approach aims to refine and expand upon existing knowledge.

Eligibility criteria

Inclusion criteria:

* Age 18 to 70 (inclusive)
* Competent to provide informed consent
* Clinical diagnosis of DM1 based on research criteria1 or positive genetic test
* Comment: The clinical research criteria require myotonia, muscle weakness in a characteristic distribution, and history of similar findings in a first degree relative. Genetic testing confirmed the diagnosis of DM1 in \> 99% of individuals who satisfied these criteria.2

Exclusion criteria:

* Symptomatic renal or liver disease, uncontrolled diabetes or thyroid disorder, or active malignancy other than skin cancer.
* Current alcohol or substance abuse
* Concurrent enrollment in clinical trial for DM1, or participation in trial within 6 months of entry.
* Concurrent pregnancy or planned pregnancy during the course of the study.
* Concurrent medical condition that would, in the opinion of the investigator or clinical evaluator, compromise performance on study measures.
* Note: non-ambulatory participants are not excluded, but are limited to \<15% of enrollment.

Inclusion criteria for participants in the muscle biopsy sub-study:

• Of the 95 patients undergoing the tibialis anterior muscle biopsy, at least half will have at least moderate weakness of ankle dorsiflexion, defined as MRC score ≤ 4+. This is in order to obtain a muscle tissue sample in a person more severely affected with myotonic dystrophy. Approximately 10 patients at each site will undergo the muscle biopsy.

Exclusion criteria for 95 participants in the muscle biopsy sub-study:

* Known CTG repeat expansion size less than 100 repeats, unless there are clear cut signs of limb weakness and muscle wasting. This is in order to obtain a muscle tissue sample in a person more severely affected with myotonic dystrophy.
* Use of anticoagulant such as warfarin or a direct oral anticoagulant (e.g. dabigatran) due to the increased risk of bleeding.
* Use of aspirin or non-steroidal anti-inflammatory agents should be discontinued 3 days prior to the biopsy procedure, if possible.
* Platelet count \<50,000 (if known) due to the increased risk of bleeding.
* History of a bleeding disorder due to the increased risk of bleeding.
* Advanced wasting of tibialis anterior (TA) muscle that precludes needle muscle biopsy in order to ensure that a sample taken would be of muscle and not just fat and fascia.
* Previous muscle biopsy of either TA in order to provide muscle tissue samples of non-biopsied muscles.

Where this trial is running

La Jolla, California and 16 other locations

• University of California, San Diego — La Jolla, California, United States (Recruiting)
• University of California, Los Angeles — Los Angeles, California, United States (Recruiting)
• University of Colorado - Denver — Denver, Colorado, United States (Recruiting)
• University of Florida — Gainesville, Florida, United States (Recruiting)
• University of Iowa — Iowa City, Iowa, United States (Recruiting)
• Kansas University Medical Center — Kansas City, Kansas, United States (Recruiting)
• University of Rochester — Rochester, New York, United States (Recruiting)
• Ohio State University — Columbus, Ohio, United States (Recruiting)
• Houston Methodist Neurological Institute — Houston, Texas, United States (Recruiting)
• Virginia Commonwealth University — Richmond, Virginia, United States (Recruiting)
• Université de Sherbrooke — Québec, Canada (Active_not_recruiting)
• Friedrich Baur Institute, Ludwig-Maximilians-Universität München — München, Germany (Recruiting)
• Centro Clinico NeMO — Milan, Italy (Completed)
• Radboud University Medical Center — Nijmegen, Netherlands (Recruiting)
• University of Auckland — Auckland, New Zealand (Recruiting)
• St. George's, University of London — London, United Kingdom (Recruiting)
• University College London — London, United Kingdom (Recruiting)

Study contacts

• Principal investigator: Nicholas Johnson, MD — Virginia Commonwealth University
• Study coordinator: Jennifer Raymond

Conditions Myotonic Dystrophy 1; DM1; Myotonic Dystrophy; END DM-1; Muscular Dystophy; DMCRN