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

February 14, 2024 updated by: Virginia Commonwealth University

Building on previous work of the Myotonic Dystrophy Clinical Research Network (DMCRN), the present study seeks to overcome insufficient data on natural history; lack of reliable biomarkers; and incomplete characterization and limited biological understanding of the phenotypic heterogeneity of Myotonic Dystrophy 1 by examining strategies to improve the reliability by making further refinements in our sample collection and analysis procedures by developing strategies for managing patient heterogeneity going forward.

Funding Source- FDA OOPD

Study Overview

Status

Recruiting

Detailed Description

Approximately 700 adult participants (18 to 70 years old, inclusive) with DM1 will be enrolled at 15 centers (up to 70 patients will be recruited at each site). No treatment will be administered as part of this study. Participants will receive standard of care as determined by the investigators. Study visits occur at baseline/0 months, 12 months, and 24 months. Few restrictions are placed on participation in the study because the investigators aim to capture the full spectrum of disease severity. Studies of splicing biomarkers in muscle biopsy samples will be conducted on a subset of 95 participants. These participants will have an additional study visit at 3 months.

Study Type

Observational

Enrollment (Estimated)

700

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

      • Québec, Canada
        • Recruiting
        • Université de Sherbrooke
        • Contact:
        • Principal Investigator:
          • Cynthia Gagnon, erg. PhD.
      • Paris, France
        • Not yet recruiting
        • Neuromuscular Reference Center Institute of Myology
        • Principal Investigator:
          • Guilaume Bazzez, MD
        • Contact:
      • München, Germany
        • Recruiting
        • Friedrich Baur Institute, Ludwig-Maximilians-Universität München
        • Contact:
        • Principal Investigator:
          • Benedikt Schoser, FEAN
      • Nijmegen, Netherlands
        • Recruiting
        • Radboud University Medical Center
        • Contact:
        • Principal Investigator:
          • Baziel van Engelen, MD
      • Auckland, New Zealand
      • London, United Kingdom
        • Recruiting
        • University College London
        • Contact:
        • Principal Investigator:
          • Chris Turner
    • California
      • La Jolla, California, United States, 92703
      • Los Angeles, California, United States, 90095
        • Recruiting
        • University of California, Los Angeles
        • Contact:
        • Principal Investigator:
          • Perry Shieh, MD, PhD
      • Stanford, California, United States, 94305
        • Recruiting
        • Stanford University
        • Contact:
        • Contact:
        • Principal Investigator:
          • John Day, MD, PhD
    • Colorado
      • Denver, Colorado, United States, 80204
    • Florida
      • Gainesville, Florida, United States, 32611
        • Recruiting
        • University of Florida
        • Contact:
        • Principal Investigator:
          • Sankarsubramoney Subramony, MD
    • Iowa
      • Iowa City, Iowa, United States, 52242
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • Recruiting
        • Kansas University Medical Center
        • Contact:
        • Principal Investigator:
          • Jeffrey Statland, MD
        • Contact:
    • Maryland
      • Bethesda, Maryland, United States, 20814
        • Completed
        • National Institute of Health NINDS
    • New York
      • Rochester, New York, United States, 14642
        • Recruiting
        • University of Rochester
        • Contact:
        • Principal Investigator:
          • Johanna Hamel, MD
    • Ohio
      • Columbus, Ohio, United States, 43210
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • Houston Methodist Hospital
        • Contact:
        • Principal Investigator:
          • Erika Simpson
    • Virginia

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Probability Sample

Study Population

DM1 has a prevalence rate of approximately 1 per 2,300. There are no expected gender differences. Both men and women will be selected for this study.

Children with DM1 are not included in this project because the pathophysiological basis of congenital and childhood DM1 appears to be mechanistically distinct.

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Other
  • Time Perspectives: Other

Cohorts and Interventions

Group / Cohort
Study Visits
Patients will receive standard of care as determined by their treating physician. Study visits occur at baseline/0 months, 12 months, and 24 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in ambulation over 24 months as measured by the 10 meter walk (m/s).
Time Frame: 12 and 24 months
10 meter walk will be measured (m/s)
12 and 24 months
Change in respiratory function over 24 months as measured by spirometry, specifically the supine forced vital capacity (FVC).
Time Frame: 12 and 24 months
Supine forced vital capacity (% predicted)
12 and 24 months
Percent splicing of DM1-affected splice events
Time Frame: 3 months
RNA sequenced of muscle biopsy samples collected at two different times will be combined and used to calculate a percent splicing index (PMI)
3 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2019

Primary Completion (Estimated)

October 1, 2026

Study Completion (Estimated)

December 1, 2026

Study Registration Dates

First Submitted

June 2, 2019

First Submitted That Met QC Criteria

June 7, 2019

First Posted (Actual)

June 11, 2019

Study Record Updates

Last Update Posted (Actual)

February 16, 2024

Last Update Submitted That Met QC Criteria

February 14, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Aggregated and deidentified data will be shared with qualified investigators upon majority approval of the DMCRN investigators.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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