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

NCT03981575 | Recruiting DMC

• 3 other identifiers: HM20014419DMCRNFD-R-006071
• Study Type: observational
• Target: 700
• Locations: 7 countries
• Sites: 17

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. Funding Source- FDA OOPD

Conditions

Myotonic Dystrophy 1; DM1

Keywords

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

Outcome Measures

Primary Outcomes (3)

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

  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).

  Supine forced vital capacity (% predicted)

  12 and 24 months

• Percent splicing of DM1-affected splice events

  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

Other Outcomes (9)

• Longitudinal Muscle Biopsy Sub-study: Characterization of RNA splicing measures over a prolonged period of time (>24 months)

  24 months

• Longitudinal Muscle Biopsy Sub-study: Characterization of functional endpoints over a prolonged period of time (>24 months)

  24 months

• COVID-19 Sub-study: Data from DM1 patients or caregivers about COVID-19 illness and vaccination experience, severity of illness and response to vaccination in DM1 patients compared to corresponding data available about the general population.

  24 months

Study Arms (1)

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

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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

You may not qualify if:

• 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.
• 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.
• 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.

Sponsors & Collaborators

• Virginia Commonwealth University: lead
• University of Rochester: collaborator
• Stanford University: collaborator
• Ohio State University: collaborator
• University of Florida: collaborator
• University of Iowa: collaborator
• Ludwig-Maximilians - University of Munich: collaborator
• Fondazione Serena Onlus - Centro Clinico NeMO Milano: collaborator
• The Methodist Hospital Research Institute: collaborator
• Radboud University Medical Center: collaborator
• University College London Hospitals: collaborator
• University of California, Los Angeles: collaborator

Study Sites (17)

University of California, San Diego

La Jolla, California, 92703, United States

RECRUITING

University of California, Los Angeles

Los Angeles, California, 90095, United States

RECRUITING

University of Colorado - Denver

Denver, Colorado, 80204, United States

RECRUITING

University of Florida

Gainesville, Florida, 32611, United States

RECRUITING

University of Iowa

Iowa City, Iowa, 52242, United States

RECRUITING

Kansas University Medical Center

Kansas City, Kansas, 66160, United States

RECRUITING

University of Rochester

Rochester, New York, 14642, United States

RECRUITING

Ohio State University

Columbus, Ohio, 43210, United States

RECRUITING

Houston Methodist Neurological Institute

Houston, Texas, 77030, United States

RECRUITING

Virginia Commonwealth University

Richmond, Virginia, 23298, 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

Related Publications (2)

• Mul K, Eichinger K, Hung M, Sansone VA, Gagnon C, Subramony S, Roxburgh RH, Hamel J, Statland JM, Elsheikh B, Turner C, Sampson J, Ragole T, Matthews E, Schoser B, Swenson A, Laverty C, Shieh P, Greene EP, Takahashi M, Wicklund M, Dekdebrun J, Raymond J, DeSpain E, Thornton CA, Johnson NE; Myotonic Dystrophy Clinical Research Network. Establishing biomarkers and clinical endpoints in myotonic dystrophy type 1 (END-DM1): Protocol of an international natural history study. PLoS One. 2025 Dec 11;20(12):e0331163. doi: 10.1371/journal.pone.0331163. eCollection 2025.

  PMID: 41379803 DERIVED

• 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.

  PMID: 39836447 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

The biopsy sub-study will examine RNA splicing defects that are characteristic of DM1.

MeSH Terms

Conditions

Myotonic Dystrophy

Condition Hierarchy (Ancestors)

Muscular Dystrophies; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Myotonic Disorders; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Nervous System Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Nicholas Johnson, MD

  Virginia Commonwealth University

  PRINCIPAL INVESTIGATOR

• Charles Thornton, MD

  University of Rochester

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jennifer Raymond

CONTACT

804-828-6318; jennifer.raymond@vcuhealth.org

Ruby Langeslay

CONTACT

804-828-8481; ruby.langeslay@vcuhealth.org

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 2, 2019
• First Posted: June 11, 2019
• Study Start: January 1, 2019
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: June 6, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1); NZ (1); GB (2); DE (1); US (10); IT (1); NL (1)