Establishing Biomarkers and Clinical Endpoints in Myotonic Dystrophy Type 1 (END-DM1)
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| ClinicalTrials.gov Identifier: NCT03981575 |
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Recruitment Status :
Recruiting
First Posted : June 11, 2019
Last Update Posted : February 8, 2023
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Sponsor:
Virginia Commonwealth University
Collaborators:
University of Rochester
The Methodist Hospital Research Institute
University of Kansas
Stanford University
Ohio State University
National Institutes of Health (NIH)
University of Florida
University of Iowa
University of California, Los Angeles
Insitut de Myologie Paris
Ludwig-Maximillians University, Munich
NEMO Clinic, Milan
University College, London
Radboud University Medical Center
Information provided by (Responsible Party):
Virginia Commonwealth University
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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.
| Condition or disease |
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| Myotonic Dystrophy 1 |
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 |
| Estimated Enrollment : | 700 participants |
| Observational Model: | Other |
| Time Perspective: | Other |
| Official Title: | Establishing Biomarkers and Clinical Endpoints in Myotonic Dystrophy Type 1 (END-DM1) |
| Actual Study Start Date : | January 1, 2019 |
| Estimated Primary Completion Date : | January 1, 2025 |
| Estimated Study Completion Date : | February 1, 2025 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Myotonic dystrophy
| Group/Cohort |
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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
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Primary Outcome Measures :
- 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)
- 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)
- 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)
Biospecimen Retention: Samples With DNA
The biopsy sub-study will examine RNA splicing defects that are characteristic of DM1.
Information from the National Library of Medicine
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| Ages Eligible for Study: | 18 Years to 70 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| 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.
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.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03981575
Contacts
| Contact: Jennifer Raymond, MD | 804-828-6318 | jennifer.raymond@vcuhealth.org | |
| Contact: Ruby Langeslay | 804-828-8481 | ruby.langeslay@vcuhealth.org |
Locations
Show 19 study locations
Sponsors and Collaborators
Virginia Commonwealth University
University of Rochester
The Methodist Hospital Research Institute
University of Kansas
Stanford University
Ohio State University
National Institutes of Health (NIH)
University of Florida
University of Iowa
University of California, Los Angeles
Insitut de Myologie Paris
Ludwig-Maximillians University, Munich
NEMO Clinic, Milan
University College, London
Radboud University Medical Center
Investigators
| Principal Investigator: | Nicholas Johnson, MD | Virginia Commonwealth University | |
| Principal Investigator: | Charles Thornton, MD | University of Rochester |
| Responsible Party: | Virginia Commonwealth University |
| ClinicalTrials.gov Identifier: | NCT03981575 |
| Other Study ID Numbers: |
HM20014419 DMCRN ( Other Identifier: University of Rochester ) |
| First Posted: | June 11, 2019 Key Record Dates |
| Last Update Posted: | February 8, 2023 |
| Last Verified: | February 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Plan Description: | Aggregated and deidentified data will be shared with qualified investigators upon majority approval of the DMCRN investigators. |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Virginia Commonwealth University:
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Myotonic Dystrophy END DM-1 Muscular Dystophy DMCRN |
Additional relevant MeSH terms:
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Myotonic Dystrophy 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 |