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Trial record 2 of 51 for:    Myotonic Dystrophy

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

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ClinicalTrials.gov Identifier: NCT03981575
Recruitment Status : Recruiting
First Posted : June 11, 2019
Last Update Posted : June 11, 2019
Sponsor:
Collaborators:
University of Rochester
The Methodist Hospital System
University of Kansas
Stanford University
Ohio State University
National Institutes of Health (NIH)
University of Florida
University of Iowa
Information provided by (Responsible Party):
Virginia Commonwealth University

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
Myotonic Dystrophy 1

Detailed Description:
Approximately 650 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.

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Study Type : Observational
Estimated Enrollment : 650 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, 2024
Estimated Study Completion Date : April 15, 2025


Group/Cohort
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



Primary Outcome Measures :
  1. 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)

  2. 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)

  3. 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 Without 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
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Contact: Nicholas Johnson, MD 804-552-0014 nicholas.johnson@vcuhealth.org
Contact: Brittney Holmberg 804-552-0014 brittney.holmberg@vuhealth.org

Locations
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United States, California
Standford University Not yet recruiting
Stanford, California, United States, 94305
Contact: Dana McDonnel    650-407-7912      
United States, Florida
University of Florida Recruiting
Gainesville, Florida, United States, 32611
Contact: Amanda Cowsert       amanda.cowsert@neurology.ufl.edu   
United States, Iowa
University of Iowa Not yet recruiting
Iowa City, Iowa, United States, 52242
Contact: Laurie Gutmann, MD       laurie-gutmann@uiowa.edu   
Principal Investigator: Laurie Gutmann, MD         
United States, Kansas
Kansas University Medical Center Recruiting
Kansas City, Kansas, United States, 66160
Contact: Jeffrey Statland, MD       jstatland@kumc.edu   
Principal Investigator: Jeffrey Statland         
United States, Maryland
National Institute of Health NINDS Not yet recruiting
Bethesda, Maryland, United States, 20814
Contact: Vanessa Ndege    301-435-9319    vanessa.ndege@nih.gov   
Principal Investigator: Ami Mankodi, MD         
United States, New York
University of Rochester Recruiting
Rochester, New York, United States, 14642
Contact: Jeanne Dekbegbrun       dekdegbrun@urmc.rochester.edu   
Principal Investigator: Charles Thornton         
United States, Ohio
Ohio State University Recruiting
Columbus, Ohio, United States, 43210
Contact: Haley Willard       haley.willard@osumc.edu   
United States, Texas
Houston Methodist Hospital Not yet recruiting
Houston, Texas, United States, 77030
Contact: S Halton       slhalton@houstonmethodist.org   
United States, Virginia
Virginia Commonwealth University Recruiting
Richmond, Virginia, United States, 23298
Contact: Liz Diaz    804-905-8540    liz.diaz@vcuhealth.org   
France
Neuromuscular Reference Center Institute of Myology Not yet recruiting
Paris, France
Contact: Guillaume Bazzez, MD       guillaume.bassez@aphp.fr   
Principal Investigator: Guilaume Bazzez, MD         
Germany
Klinikum der Universität München Not yet recruiting
München, Germany
Contact: Benedikt Schoser    +49 (0)89 4400 57400    max.mustermann@med.uni-muenchen.de   
Principal Investigator: Benedikt Schoser, FEAN         
Italy
NEMO Not yet recruiting
Milan, Italy
Contact: Luca Mauro       luca.mauro@centrocliniconemo.it   
Principal Investigator: Valeria Sansone, MD         
Netherlands
Radboud University Medical Center Not yet recruiting
Nijmegen, Netherlands
Contact: Baziel vanEngelen    (024) 366 8374    Baziel.vanEngelen@radboudumc.nl   
Principal Investigator: Baziel van Engelen, MD         
United Kingdom
Newcastle University Not yet recruiting
Newcastle, United Kingdom
Contact: Volker Straub, MD       volker.straub@newcastle.ac.uk   
Principal Investigator: Volker Straub, MD         
Sponsors and Collaborators
Virginia Commonwealth University
University of Rochester
The Methodist Hospital System
University of Kansas
Stanford University
Ohio State University
National Institutes of Health (NIH)
University of Florida
University of Iowa
Investigators
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Principal Investigator: Nicholas Johnson, MD Virginia Commonwealth University
Principal Investigator: Charles Thornton, MD University of Rochester

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Responsible Party: Virginia Commonwealth University
ClinicalTrials.gov Identifier: NCT03981575     History of Changes
Other Study ID Numbers: HM20014419
DMCRN ( Other Identifier: University of Rochester )
First Posted: June 11, 2019    Key Record Dates
Last Update Posted: June 11, 2019
Last Verified: June 2019
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.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Virginia Commonwealth University:
Myotonic Dystrophy
END DM-1
Muscular Dystophy
DMCRN
Additional relevant MeSH terms:
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Myotonic Dystrophy
Muscular Dystrophies
Myotonic Disorders
Muscular Disorders, Atrophic
Muscular Diseases
Musculoskeletal Diseases
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Nervous System Diseases
Neuromuscular Diseases
Genetic Diseases, Inborn