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

NCT ID: NCT03981575

Last Updated: 2025-06-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

700 participants

Study Classification

OBSERVATIONAL

Study Start Date

2019-01-01

Study Completion Date

2026-12-01

Brief Summary

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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

Detailed Description

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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.

Muscle biopsy sub-study: 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.

Longitudinal muscle biopsy sub-study: Up to 30 individuals who have had a prior muscle biopsy as part of a DMCRN study will be asked to undergo another biopsy greater than 24 months after the prior biopsy. These participants will have an additional ad hoc biopsy visit.

COVID-19 sub-study: To evaluate severity of illness and response to COVID-19 vaccination in DM1 patients compared to corresponding data available about the general population, END-DM1 study participants will be asked to complete a one-time survey about COVID-19 experiences. A subset of those participants' blood samples will be analyzed to understand immunoglobulin response to infection and vaccination in DM1 patients.

Actigraphy sub-study: To assess daily physical activity in individuals with DM1 and evaluate physical activity changes over a 12-24 month period related to disease progression, a subset of participants will be asked to wear a small, wireless activity monitor while performing functional assessments described in the main study. Those participants will be asked to wear the activity monitor for 7 days following their research visit. Those participants will be asked to complete additional questionnaires.

Handheld Dynamometry sub-study: To evaluate additional muscle strength methods, a subset of participants will be asked to complete additional strength testing using either the MEDup or MicroFET handheld dynamometry device on the same day as their END-DM1 main study visit. Those participants will be asked to return to the clinic for a second visit within 10 days of the END-DM1 study visit to repeat the handheld dynamometry assessments and complete additional strength measures.

Conditions

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Myotonic Dystrophy 1 DM1

Study Design

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Observational Model Type

OTHER

Study Time Perspective

PROSPECTIVE

Study Groups

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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

No interventions assigned to this group

Eligibility Criteria

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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


• 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

* 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.


* 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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Rochester

OTHER

Sponsor Role collaborator

Stanford University

OTHER

Sponsor Role collaborator

Ohio State University

OTHER

Sponsor Role collaborator

University of Florida

OTHER

Sponsor Role collaborator

University of Iowa

OTHER

Sponsor Role collaborator

Ludwig-Maximilians - University of Munich

OTHER

Sponsor Role collaborator

Fondazione Serena Onlus - Centro Clinico NeMO Milano

OTHER

Sponsor Role collaborator

The Methodist Hospital Research Institute

OTHER

Sponsor Role collaborator

Radboud University Medical Center

OTHER

Sponsor Role collaborator

University College London Hospitals

OTHER

Sponsor Role collaborator

University of California, Los Angeles

OTHER

Sponsor Role collaborator

Virginia Commonwealth University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Nicholas Johnson, MD

Role: PRINCIPAL_INVESTIGATOR

Virginia Commonwealth University

Charles Thornton, MD

Role: PRINCIPAL_INVESTIGATOR

University of Rochester

Locations

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University of California, San Diego

La Jolla, California, United States

Site Status RECRUITING

University of California, Los Angeles

Los Angeles, California, United States

Site Status RECRUITING

University of Colorado - Denver

Denver, Colorado, United States

Site Status RECRUITING

University of Florida

Gainesville, Florida, United States

Site Status RECRUITING

University of Iowa

Iowa City, Iowa, United States

Site Status RECRUITING

Kansas University Medical Center

Kansas City, Kansas, United States

Site Status RECRUITING

University of Rochester

Rochester, New York, United States

Site Status RECRUITING

Ohio State University

Columbus, Ohio, United States

Site Status RECRUITING

Houston Methodist Neurological Institute

Houston, Texas, United States

Site Status RECRUITING

Virginia Commonwealth University

Richmond, Virginia, United States

Site Status RECRUITING

Université de Sherbrooke

Québec, , Canada

Site Status ACTIVE_NOT_RECRUITING

Friedrich Baur Institute, Ludwig-Maximilians-Universität München

München, , Germany

Site Status RECRUITING

Centro Clinico NeMO

Milan, , Italy

Site Status COMPLETED

Radboud University Medical Center

Nijmegen, , Netherlands

Site Status RECRUITING

University of Auckland

Auckland, , New Zealand

Site Status RECRUITING

St. George's, University of London

London, , United Kingdom

Site Status RECRUITING

University College London

London, , United Kingdom

Site Status RECRUITING

Countries

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United States Canada Germany Italy Netherlands New Zealand United Kingdom

Central Contacts

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Jennifer Raymond

Role: CONTACT

804-828-6318

Ruby Langeslay

Role: CONTACT

804-828-8481

Facility Contacts

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Elizabeth Moreno

Role: primary

Gabriella Penner

Role: backup

Dennis Fernando

Role: primary

310-825-3264

Alyssa Avilez

Role: primary

303-724-4644

Brianna Blume

Role: backup

303-724-6386

Whitney Miller

Role: primary

Donovan Lott

Role: backup

Maegan Tyrrell

Role: primary

319-356-8323

Loraine Brenner

Role: backup

Rebecca Clay

Role: primary

Michaela Walker

Role: backup

Jim Hilbert

Role: primary

585-273-5590

Jeanne Dekdebrun

Role: backup

585-276-4611

Kaneshia Hives

Role: primary

614-685-5661

Lischele Watkins

Role: backup

Kadeesia Brown

Role: primary

346-238-2295

Carino Jennings

Role: primary

Jodie Howell

Role: backup

Benedikt Schoser

Role: primary

+49 (0)89 4400 57400

Corinna Wirner-Piotrowski

Role: backup

+49 89 4400 57400

Baziel vanEngelen

Role: primary

(024) 366 8374

Monique Plieger

Role: backup

Neerja Singh

Role: primary

Miriam Rodrigues

Role: backup

021896662

Emma Matthews

Role: primary

020 8725 4162

Chris Turner

Role: primary

Iqraa Afzal

Role: backup

References

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Provenzano M, Ikegami K, Bates K, Gaynor A, Hartman JM, Jones A, Butler A, Berggren KN, Dekdebrun J, Hung M, Lapato DM, Kiefer M, Thornton CA, Johnson NE, Hale MA; Myotonic Dystrophy Clinical Research Network (DMCRN). The Splice Index as a prognostic biomarker of strength and function in myotonic dystrophy type 1. J Clin Invest. 2025 Jan 7;135(4):e185426. doi: 10.1172/JCI185426.

Reference Type DERIVED
PMID: 39836447 (View on PubMed)

Other Identifiers

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DMCRN

Identifier Type: OTHER

Identifier Source: secondary_id

FD-R-006071

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

HM20014419

Identifier Type: -

Identifier Source: org_study_id

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