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Trial record 6 of 14 for:    Recruiting, Not yet recruiting, Active, not recruiting, Enrolling by invitation Studies | Myotonic Dystrophy

Venous Thromboembolism in Myotonic Dystrophy Type 1 (DM1-VTE)

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ClinicalTrials.gov Identifier: NCT03424460
Recruitment Status : Not yet recruiting
First Posted : February 7, 2018
Last Update Posted : March 14, 2018
Sponsor:
Collaborators:
AFM-Téléthon (Funding)
Recherche Clinique Paris Descartes Necker Cochin Sainte Anne
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

Brief Summary:

Investigators identified a high risk of deep vein thrombosis and pulmonary embolism in patients presenting myotonic dystrophy type 1 treated in our hospital, 10 times higher than general population matched on age and sex. These venous thromboembolic events were frequently severe and lethal.

Investigators suspect that this high risk of venous thromboembolism is due to coagulation abnormalities specific to myotonic dystrophy type 1.

The purpose of this study is to determine: 1/ if there is a hypercoagulable state in myotonic dystrophy type 1 by testing patient's coagulation, and 2/ if genes encoding factors involved in coagulation have modified expression resulting in this hypercoagulable state.

Understanding the pathophysiology will help preventing venous thromboembolism in these patients.

It is the first study to describe this specific issue.


Condition or disease Intervention/treatment Phase
Myotonic Dystrophy 1 Biological: Haemostasis tests Biological: Monocytes and megacaryocytes culture and RNA extraction Genetic: RNA extraction Not Applicable

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 69 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Two populations:

  • Population n°1: prospective, with 3 arms
  • Population n°2: retrospective, with 2 arms
Masking: None (Open Label)
Primary Purpose: Other
Official Title: Venous Thromboembolism in Myotonic Dystrophy Type 1
Estimated Study Start Date : April 2018
Estimated Primary Completion Date : April 2019
Estimated Study Completion Date : July 2019


Arm Intervention/treatment
Experimental: population 1-A1 : DM1 with VTE
Myotonic dystrophy type 1 patients with a history of venous thromboembolism (pulmonary embolism and/or deep vein thrombosis)
Biological: Haemostasis tests
Venipuncture of 30 milliliters of blood. The following tests will be performed: thromboelastography (TEG®), standard tests of coagulation, genetic thrombophilia, lupus anticoagulant, fibrinolysis markers (Alpha-2-antiplasmin, amidolytic activity, plasmin anti-plasmin complexes, Plasminogen Activator Inhibitor-1 (PAI-1) antigen, plasminogen amydolytic activity), and a global test of fibrinolytic activity.

Biological: Monocytes and megacaryocytes culture and RNA extraction
Venipuncture of 60 milliliters of blood. Monocytes and megacaryocytes culture. RNA extraction from monocytes and megacaryocytes.

Active Comparator: population 1-B1 : DM1 without VTE
Myotonic dystrophy type 1 patients without a history of venous thromboembolism
Biological: Haemostasis tests
Venipuncture of 30 milliliters of blood. The following tests will be performed: thromboelastography (TEG®), standard tests of coagulation, genetic thrombophilia, lupus anticoagulant, fibrinolysis markers (Alpha-2-antiplasmin, amidolytic activity, plasmin anti-plasmin complexes, Plasminogen Activator Inhibitor-1 (PAI-1) antigen, plasminogen amydolytic activity), and a global test of fibrinolytic activity.

Biological: Monocytes and megacaryocytes culture and RNA extraction
Venipuncture of 60 milliliters of blood. Monocytes and megacaryocytes culture. RNA extraction from monocytes and megacaryocytes.

Active Comparator: population 1-C1 : Healthy volunteers
Healthy volunteers without any medical history or treatment
Biological: Haemostasis tests
Venipuncture of 30 milliliters of blood. The following tests will be performed: thromboelastography (TEG®), standard tests of coagulation, genetic thrombophilia, lupus anticoagulant, fibrinolysis markers (Alpha-2-antiplasmin, amidolytic activity, plasmin anti-plasmin complexes, Plasminogen Activator Inhibitor-1 (PAI-1) antigen, plasminogen amydolytic activity), and a global test of fibrinolytic activity.

Biological: Monocytes and megacaryocytes culture and RNA extraction
Venipuncture of 60 milliliters of blood. Monocytes and megacaryocytes culture. RNA extraction from monocytes and megacaryocytes.

Experimental: population 2-A2 : DM1 liver samples
Liver samples of patients with myotonic dystrophy type 1
Genetic: RNA extraction
RNA extraction from liver tissue

Active Comparator: population 2-B2 : Healthy liver samples
Liver samples from patients without any medical history
Genetic: RNA extraction
RNA extraction from liver tissue




Primary Outcome Measures :
  1. Results of thromboelastography in the 3 arms of population n°1 [ Time Frame: 12 months ]
    Results given in thromboelastography traces


Secondary Outcome Measures :
  1. Results of prothrombin time (PT) and activated partial thromboplastin time (APPT) in the 3 arms of population n°1 [ Time Frame: 18 months ]
    Results given in seconds

  2. Results of plasma fibrinogen levels in the 3 arms of population n°1 [ Time Frame: 12 months ]
    Results given in grams per liter

  3. Results of thrombophilia testing in the 3 arms of population n°1 [ Time Frame: 12 months ]

    Testing for:

    • Antithrombin III mutation
    • C protein mutation
    • S protein mutaiton
    • Activated C protein resistance mutation
    • Factor II G20210 mutation
    • Lupus anticoagulant. Results given in: presence or absence (yes or no)

  4. Results of the following fibrinolytic markers: alpha-2-antiplasmine, amidolytic activity, PAI-1 antigen, plasminogen amydolytic activity in the 3 arms of population n°1 [ Time Frame: 12 months ]
    Results given in International Units per milliliters

  5. Results of levels of plasmin anti-plasmin complexes [ Time Frame: 12 months ]
    Results given in picograms per milliliters

  6. Results of global test of fibrinolytic activity by the method of von Kaulla [ Time Frame: 12 months ]
    Results given in hours

  7. Evaluation of coagulation and/or fibrinolysis genes' expression and alternative splicing in the 3 arms of population n°1 and in the 2 arms of population n°2 [ Time Frame: 18 months ]

    Bioanalysis of the patients' transcriptomes after global RNA sequencing, focusing on expression or alternative splicing misregulation of coagulation and/or fibrinolysis genes.

    Results given in : gene name(s) and description




Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Population N°1

    • Age over 18 years
    • Patient living in France and with medical insurance
    • Patient having given his informed and written consent
    • DM1 groups: genetically proven DM1
    • VTE groups: at least 1 history of VTE (PE and/or DVT)
    • Healthy volunteers: patient without any medical history (no DM1, no VTE, no thrombophilia), and without taking any anti-thrombotic medication
  2. Population N°2

    • Liver tissue of patients with genetically proven DM1 (tissue bank)
    • Liver tissue of patients without DM1 or any history of VTE (tissue bank)

Exclusion Criteria:

  • Patient opposed to data collection and analysis

    1. Population N°1

  • Genetically proven thrombophilia
  • Anti-thrombotic medication
  • Hemoglobin levels < 7 g/dL
  • Hemoglobin levels < 9 g/dL in case of cardiac of respiratory condition

    2. Population N°2

  • Liver tissue quality insufficient for RNA extraction and analysis

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): NCT03424460


Contacts
Contact: Karim Wahbi, MD, PhD +33 (0)1 58 41 16 63 karim.wahbi@aphp.fr
Contact: Adèle Bellino +33 (0)1 58 41 11 95 adele.bellino@aphp.fr

Locations
France
Service de Cardiologie - Hôpital Cochin Not yet recruiting
Paris, Ile De France, France, 75014
Contact: Karim Wahbi, MD, PhD    +33 (0)1 58 41 16 63    karim.wahbi@aphp.fr   
Contact: Denis Duboc, MD, PhD    +33 (0)1 58 41 16 53    denis.duboc@aphp.fr   
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
AFM-Téléthon (Funding)
Recherche Clinique Paris Descartes Necker Cochin Sainte Anne
Investigators
Principal Investigator: Karim Wahbi, MD, PhD Assistance Publique Hôpitaux de Paris (AP-HP)
Study Director: Denis Duboc, MD, PhD Assistance Publique Hôpitaux de Paris (AP-HP)
Study Chair: Michaela Fontenay, MD, PhD Assistance Publique Hôpitaux de Paris (AP-HP)
Principal Investigator: Denis Furling, Md, PhD Université Paris 6 Pierre et Marie Curie

Publications:

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT03424460     History of Changes
Other Study ID Numbers: K170601J
2017-A01634-49 ( Registry Identifier: ID-RCB )
First Posted: February 7, 2018    Key Record Dates
Last Update Posted: March 14, 2018
Last Verified: March 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Myotonic dystrophy 1
Venous thromboembolism
Pulmonary embolism
Deep vein thrombosis
Hypercoagulability
Thrombophilia
RNA alternative splicing

Additional relevant MeSH terms:
Myotonic Dystrophy
Muscular Dystrophies
Myotonic Disorders
Thromboembolism
Venous Thromboembolism
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases
Muscular Disorders, Atrophic
Muscular Diseases
Musculoskeletal Diseases
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Nervous System Diseases
Neuromuscular Diseases
Genetic Diseases, Inborn