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

Myotonic Dystrophy 1 Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03981575
• Other study ID #: HM20014419
• Secondary ID: DMCRNFD-R-006071
• Status: Recruiting
• Start date: January 1, 2019
• Est. completion date: December 1, 2026

Study information

• Verified date: April 2024
• Source: Virginia Commonwealth University
• Contact: Jennifer Raymond
• Phone: 804-828-6318
• Email: jennifer.raymond[@]vcuhealth.org
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 700
• Est. completion date: December 1, 2026
• Est. primary completion date: October 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Myotonic Dystrophy
• Myotonic Dystrophy 1

Locations

Country	Name	City	State
Canada	Université de Sherbrooke	Québec
France	Neuromuscular Reference Center Institute of Myology	Paris
Germany	Friedrich Baur Institute, Ludwig-Maximilians-Universität München	München
Italy	Centro Clinico NeMO	Milan
Netherlands	Radboud University Medical Center	Nijmegen
New Zealand	University of Auckland	Auckland
United Kingdom	St. George's, University of London	London
United Kingdom	University College London	London
United States	National Institute of Health NINDS	Bethesda	Maryland
United States	Ohio State University	Columbus	Ohio
United States	University of Colorado - Denver	Denver	Colorado
United States	University of Florida	Gainesville	Florida
United States	Houston Methodist Neurological Institute	Houston	Texas
United States	University of Iowa	Iowa City	Iowa
United States	Kansas University Medical Center	Kansas City	Kansas
United States	University of California, San Diego	La Jolla	California
United States	University of California, Los Angeles	Los Angeles	California
United States	Virginia Commonwealth University	Richmond	Virginia
United States	University of Rochester	Rochester	New York
United States	Stanford University	Stanford	California

Sponsors (13)

Lead Sponsor	Collaborator
Virginia Commonwealth University	Fondazione Serena Onlus - Centro Clinico NeMO Milano, Ludwig-Maximilians - University of Munich, Ohio State University, Radboud University Medical Center, Stanford University, The Methodist Hospital Research Institute, University College, London, University of California, Los Angeles, University of Florida, University of Iowa, University of Kansas, University of Rochester

Countries where clinical trial is conducted

United States,  Canada,  France,  Germany,  Italy,  Netherlands,  New Zealand,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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