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

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Brief Title

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

Official Title

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

Brief Summary

      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.
    

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


Primary Outcome

Change in ambulation over 24 months as measured by the 10 meter walk (m/s).


Condition

Myotonic Dystrophy 1


Study Arms / Comparison Groups

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

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information



Estimated Enrollment

700

Start Date

January 1, 2019

Completion Date

April 15, 2025

Primary Completion Date

January 1, 2024

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.
      

Gender

All

Ages

18 Years - 70 Years

Accepts Healthy Volunteers

No

Contacts

Nicholas Johnson, MD, 804-552-0014, [email protected]

Location Countries

France

Location Countries

France

Administrative Informations


NCT ID

NCT03981575

Organization ID

HM20014419

Secondary IDs

DMCRN

Responsible Party

Sponsor

Study Sponsor

Virginia Commonwealth University

Collaborators

 University of Rochester

Study Sponsor

Nicholas Johnson, MD, Principal Investigator, Virginia Commonwealth University


Verification Date

December 2021