Venous Thromboembolism in Myotonic Dystrophy Type 1

NCT03424460 | Completed

• 2 other identifiers: K170601J2017-A01634-49
• Study Type: interventional
• Target: 130
• Locations: 1 country
• Sites: 1

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.

Conditions

Myotonic Dystrophy 1

Keywords

Myotonic dystrophy 1; Venous thromboembolism; Pulmonary embolism; Deep vein thrombosis; Hypercoagulability; Thrombophilia; RNA alternative splicing

Outcome Measures

Primary Outcomes (1)

• Results of thromboelastography in the 3 arms of population n°1

  Results given in thromboelastography traces

  24 months

Secondary Outcomes (7)

• Results of prothrombin time (PT) and activated partial thromboplastin time (APPT) in the 3 arms of population n°1

  30 months

• Results of plasma fibrinogen levels in the 3 arms of population n°1

  24 months

• Results of thrombophilia testing in the 3 arms of population n°1

  24 months

• 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

  24 months

• Results of levels of plasmin anti-plasmin complexes

  24 months

Study Arms (5)

population 1-A1 : DM1 with VTE

EXPERIMENTAL

Myotonic dystrophy type 1 patients with a history of venous thromboembolism (pulmonary embolism and/or deep vein thrombosis)

Biological: Haemostasis tests; Biological: Monocytes and megacaryocytes culture and RNA extraction

population 1-B1 : DM1 without VTE

ACTIVE COMPARATOR

Myotonic dystrophy type 1 patients without a history of venous thromboembolism

Biological: Haemostasis tests; Biological: Monocytes and megacaryocytes culture and RNA extraction

population 1-C1 : Healthy volunteers

ACTIVE COMPARATOR

Healthy volunteers without any medical history or treatment

Biological: Haemostasis tests; Biological: Monocytes and megacaryocytes culture and RNA extraction

population 2-A2 : DM1 liver samples

EXPERIMENTAL

Liver samples of patients with myotonic dystrophy type 1

Genetic: RNA extraction

population 2-B2 : Healthy liver samples

ACTIVE COMPARATOR

Liver samples from patients without any medical history

Genetic: RNA extraction

Interventions

Haemostasis tests BIOLOGICAL

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.

population 1-A1 : DM1 with VTE; population 1-B1 : DM1 without VTE; population 1-C1 : Healthy volunteers

Monocytes and megacaryocytes culture and RNA extraction BIOLOGICAL

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

population 1-A1 : DM1 with VTE; population 1-B1 : DM1 without VTE; population 1-C1 : Healthy volunteers

RNA extraction GENETIC

RNA extraction from liver tissue

population 2-A2 : DM1 liver samples; population 2-B2 : Healthy liver samples

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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)

You may not qualify if:

• Patient opposed to data collection and analysis
• \. 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
• \. Population N°2
• Liver tissue quality insufficient for RNA extraction and analysis

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• AFM-Téléthon (Funding): collaborator
• Recherche Clinique Paris Descartes Necker Cochin Sainte Anne: collaborator
• URC-CIC Paris Descartes Necker Cochin: collaborator

Study Sites (1)

Service de Cardiologie - Hôpital Cochin

Paris, Île-de-France Region, 75014, France

Location

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MeSH Terms

Conditions

Myotonic Dystrophy; Venous Thromboembolism; Pulmonary Embolism; Venous Thrombosis; Thrombophilia

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; Thromboembolism; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Lung Diseases; Respiratory Tract Diseases; Embolism; Thrombosis; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Karim Wahbi, MD, PhD

  Assistance Publique Hôpitaux de Paris (AP-HP)

  PRINCIPAL INVESTIGATOR

• Denis Duboc, MD, PhD

  Assistance Publique Hôpitaux de Paris (AP-HP)

  STUDY DIRECTOR

• Michaela Fontenay, MD, PhD

  Assistance Publique Hôpitaux de Paris (AP-HP)

  STUDY CHAIR

• Denis Furling, Md, PhD

  Université Paris 6 Pierre et Marie Curie

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Two populations: * Population n°1: prospective, with 3 arms * Population n°2: retrospective, with 2 arms

Study Record Dates

• First Submitted: December 7, 2017
• First Posted: February 7, 2018
• Study Start: June 11, 2018
• Primary Completion: March 15, 2023
• Study Completion: March 15, 2023
• Last Updated: September 12, 2025

Record last verified: 2025-09

Locations

FR (1)