Myotonic Dystrophy 1DM1-VTENCT03424460
Venous Thromboembolism in Myotonic Dystrophy Type 1
A study testing Haemostasis tests, Monocytes and megacaryocytes culture and RNA extraction and RNA extraction in people with Myotonic Dystrophy 1, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Myotonic Dystrophy 1
- What is being tested?
- Haemostasis tests, Monocytes and megacaryocytes culture and RNA extraction and RNA extraction
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 130 participants
- Where
- 1 siteFrance
- Study dates
- 11 Jun 2018to 15 Mar 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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)
Show all 10Show fewer
- 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)
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
France1 site
Service de Cardiologie - Hôpital Cochin
Paris, Île-de-France Region, 75014
About this study
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.
Read more
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.
Read the detailed description
Investigators have identified in the cohort of 1084 patients presenting myotonic dystrophy type 1 (DM1) a 10% prevalence of venous thromboembolism (VTE) and a 7‰ annual incidence, which is 10-fold higher than in the general population and 3-fold compared to patients with other myopathies.
Patients' clinical presentations were very similar to those observed in patients with severe hypercoagulable states caused by mutations in genes encoding factors involved in coagulation, fibrinolysis or their regulation and represented a frequent cause of death.
To Investigator's knowledge, this association between VTE and DM1 has never been reported to date and no competing project has been initiated on this topic by any other team.
Investigators hypothesize that VTE in DM1 may be related to a hypercoagulable state resulting from an imbalance between coagulation processes and fibrinolysis properties. Because the expression of pathogenic CTG repeats in DM1 leads to a RNA gain-of-function mechanism, Investigators propose these abnormalities may be the consequence of alternative splicing misregulation and/or abnormal gene expression of coagulation, fibrinolysis factors or other factors involved in their regulation.
Investigators applied a candidate gene strategy to screen splicing profiles of 33 genes coding for haemostasis factors in a DM1 context. Using expression large-scale datasets of DM1 tissue samples from skeletal muscle and heart, Investigators identified splicing defects in 4 genes involved in haemostasis, in particular 3 involved in the fibrinolytic system: PLAT, PLAU and SERPINE1. These preliminary analyses were however not performed on liver samples whereas genes coding for haemostasis factors are synthesized and mainly expressed in liver. Analysis of liver and monocytes/megacaryotes RNA samples appears to be an essential step.
The objectives are to (i) study haemostatic properties of a cohort of patients with DM1 with and without personal history of VTE, in order to determine whether a hypercoagulable state may be associated with DM1 and whether it may be correlated to the occurrence of VTE, and (ii) to perform a global transcriptomic approach using massive parallel sequencing (RNAseq) on liver and monocytes/megacaryotes. RNA samples obtained from DM1 patients will help identify candidate genes with altered expression or alternative splicing misregulation that may underlie VTE in DM1.
The study will include two complementary parts in DM1 patients with and without personal history of VTE and healthy volunteers: haemostasis tests, and transcriptomic analysis on RNA samples isolated from liver biopsies and blood monocytes/megacaryocytes samples.Three teams will be involved in the study: Team 1 (clinical study), Team 2 (haematology) and Team 3 (transcriptomic analysis).
Haemostasis tests will be performed by Team 1 and analysed by Team 2 in (i) 100 patients prospectively enrolled in Investigator's Institution by Team 1, aged >18 years, with genetically proven DM1, after providing written informed consent, without any current antithrombotic treatment, including 80 without and 20 with personal history of VTE and (ii) 30 healthy volunteers matched on age and sex. RNAseq will be performed on (i) liver tissue issued from 3 patients with DM1 and 6 controls and (ii) monocytes/megacaryocytes isolated from the blood of 15 patients with DM1 (7 with and 8 without VTE) and 15 controls prospectively enrolled in the study. Inclusion and exclusion criteria will be similar to those of patients included in the study of haemostasis properties.
Liver tissues are already available in a tissue bank. Blood will be prospectively collected in DM1 patients and controls by Team 1. Monocytes and megacaryocytes will be isolated and cultured by Team 2.
Team 3 will extract total RNA from liver samples, monocytes and megacaryocytes to the Centre National de Génotypage for RNA sequencing and perform the analysis of the data and the validation of the newly identified candidates.
The estimated study duration is 72 months, including (i) 66 months for patient inclusions, coagulation testsand monocytes/megacaryocytes isolations, and (ii) 6 months for fibrinolysis tests, RNA extraction and sequencing, data analysis, validation.
Investigators believe the study will have important implications for the clinical management of patients with DM1. Specific strategies will be proposed for the prevention of VTE with potentially larger indications for prophylactic anticoagulant treatments and longer duration after a first episode of VTE.
Regarding the high mortality associated with VTE and the identification in the registry of pulmonary embolism as a frequent cause of death, sudden and non-sudden, in DM1 patients, the modification of these treatment strategies may be associated with an important clinical benefit.The identification of haemostasis abnormalities by coagulation and fibrinolysis tests could be useful for risk stratification in patients with DM1 and could allow targeted treatments.
- Conditions
- Myotonic Dystrophy 1
- Being tested
- Haemostasis tests, Monocytes and megacaryocytes culture and RNA extraction, RNA extraction
- Keywords
- Myotonic dystrophy 1, Venous thromboembolism, Pulmonary embolism, Deep vein thrombosis, Hypercoagulability, Thrombophilia, RNA alternative splicing
- Medical subject headings
- Myotonic Dystrophy, Venous Thromboembolism, Pulmonary Embolism, Venous Thrombosis, Thrombophilia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Haemostasis testsBiological
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.
Monocytes and megacaryocytes culture and RNA extractionBiological
Venipuncture of 60 milliliters of blood. Monocytes and megacaryocytes culture. RNA extraction from monocytes and megacaryocytes.
RNA extractionGenetic
RNA extraction from liver tissue
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: 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 Receives: 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 Receives: 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 Receives: Genetic: RNA extraction |
| population 2-B2 : Healthy liver samples | Active comparator | Liver samples from patients without any medical history Receives: Genetic: RNA extraction |
What is being measured
The primary outcome is the main question the study is designed to answer.
Results of thromboelastography in the 3 arms of population n°1
Results given in thromboelastography traces
Measured: 24 months
Secondary outcomes (7)
Results of prothrombin time (PT) and activated partial thromboplastin time (APPT) in the 3 arms of population n°1
Results given in seconds
Measured: 30 months
Results of plasma fibrinogen levels in the 3 arms of population n°1
Results given in grams per liter
Measured: 24 months
Results of thrombophilia testing in the 3 arms of population n°1
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)
Measured: 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
Results given in International Units per milliliters
Measured: 24 months
Results of levels of plasmin anti-plasmin complexes
Results given in picograms per milliliters
Measured: 24 months
Results of global test of fibrinolytic activity by the method of von Kaulla
Results given in hours
Measured: 24 months
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
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
Measured: 30 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Feb 2018
- Study start11 Jun 2018
- Primary completion15 Mar 2023
- Study completion15 Mar 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (26)Papers the sponsor has linked to this study.
- Other trials for Myotonic Dystrophy 1Studies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Two populations: * Population n°1: prospective, with 3 arms * Population n°2: retrospective, with 2 arms
- Masking
- None (open label)
- Enrolment
- 130 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- AFM-Téléthon (Funding), Recherche Clinique Paris Descartes Necker Cochin Sainte Anne, URC-CIC Paris Descartes Necker Cochin
- Responsible party
- Sponsor
- Investigators
- Karim Wahbi, MD, PhD, Principal investigator, Assistance Publique Hôpitaux de Paris (AP-HP)Denis Duboc, MD, PhD, Study director, Assistance Publique Hôpitaux de Paris (AP-HP)Michaela Fontenay, MD, PhD, Study chair, Assistance Publique Hôpitaux de Paris (AP-HP)Denis Furling, Md, PhD, Principal investigator, Université Paris 6 Pierre et Marie Curie
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03424460
- Sponsor's protocol ID
- K170601J
- Other IDs
- 2017-A01634-49
- Acronym
- DM1-VTE
- Status last verified
- Sep 2025
- First submitted
- 7 Dec 2017
- Last updated
- 12 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Udd B, Krahe R. The myotonic dystrophies: molecular, clinical, and therapeutic challenges. Lancet Neurol. 2012 Oct;11(10):891-905. doi: 10.1016/S1474-4422(12)70204-1.
PubMed 22995693Mathieu J, De Braekeleer M, Prevost C. Genealogical reconstruction of myotonic dystrophy in the Saguenay-Lac-Saint-Jean area (Quebec, Canada). Neurology. 1990 May;40(5):839-42. doi: 10.1212/wnl.40.5.839.
PubMed 2330114Fu YH, Pizzuti A, Fenwick RG Jr, King J, Rajnarayan S, Dunne PW, Dubel J, Nasser GA, Ashizawa T, de Jong P, et al. An unstable triplet repeat in a gene related to myotonic muscular dystrophy. Science. 1992 Mar 6;255(5049):1256-8. doi: 10.1126/science.1546326.
PubMed 1546326Mahadevan M, Tsilfidis C, Sabourin L, Shutler G, Amemiya C, Jansen G, Neville C, Narang M, Barcelo J, O'Hoy K, et al. Myotonic dystrophy mutation: an unstable CTG repeat in the 3' untranslated region of the gene. Science. 1992 Mar 6;255(5049):1253-5. doi: 10.1126/science.1546325.
PubMed 1546325Brook JD, McCurrach ME, Harley HG, Buckler AJ, Church D, Aburatani H, Hunter K, Stanton VP, Thirion JP, Hudson T, et al. Molecular basis of myotonic dystrophy: expansion of a trinucleotide (CTG) repeat at the 3' end of a transcript encoding a protein kinase family member. Cell. 1992 Feb 21;68(4):799-808. doi: 10.1016/0092-8674(92)90154-5.
PubMed 1310900Day JW, Ranum LP. RNA pathogenesis of the myotonic dystrophies. Neuromuscul Disord. 2005 Jan;15(1):5-16. doi: 10.1016/j.nmd.2004.09.012. Epub 2004 Nov 26.
PubMed 15639115Mankodi A, Logigian E, Callahan L, McClain C, White R, Henderson D, Krym M, Thornton CA. Myotonic dystrophy in transgenic mice expressing an expanded CUG repeat. Science. 2000 Sep 8;289(5485):1769-73. doi: 10.1126/science.289.5485.1769.
PubMed 10976074Tian B, White RJ, Xia T, Welle S, Turner DH, Mathews MB, Thornton CA. Expanded CUG repeat RNAs form hairpins that activate the double-stranded RNA-dependent protein kinase PKR. RNA. 2000 Jan;6(1):79-87. doi: 10.1017/s1355838200991544.
PubMed 10668800Charizanis K, Lee KY, Batra R, Goodwin M, Zhang C, Yuan Y, Shiue L, Cline M, Scotti MM, Xia G, Kumar A, Ashizawa T, Clark HB, Kimura T, Takahashi MP, Fujimura H, Jinnai K, Yoshikawa H, Gomes-Pereira M, Gourdon G, Sakai N, Nishino S, Foster TC, Ares M Jr, Darnell RB, Swanson MS. Muscleblind-like 2-mediated alternative splicing in the developing brain and dysregulation in myotonic dystrophy. Neuron. 2012 Aug 9;75(3):437-50. doi: 10.1016/j.neuron.2012.05.029.
PubMed 22884328Nakamori M, Sobczak K, Puwanant A, Welle S, Eichinger K, Pandya S, Dekdebrun J, Heatwole CR, McDermott MP, Chen T, Cline M, Tawil R, Osborne RJ, Wheeler TM, Swanson MS, Moxley RT 3rd, Thornton CA. Splicing biomarkers of disease severity in myotonic dystrophy. Ann Neurol. 2013 Dec;74(6):862-72. doi: 10.1002/ana.23992.
PubMed 23929620Mankodi A, Takahashi MP, Jiang H, Beck CL, Bowers WJ, Moxley RT, Cannon SC, Thornton CA. Expanded CUG repeats trigger aberrant splicing of ClC-1 chloride channel pre-mRNA and hyperexcitability of skeletal muscle in myotonic dystrophy. Mol Cell. 2002 Jul;10(1):35-44. doi: 10.1016/s1097-2765(02)00563-4.
PubMed 12150905Fugier C, Klein AF, Hammer C, Vassilopoulos S, Ivarsson Y, Toussaint A, Tosch V, Vignaud A, Ferry A, Messaddeq N, Kokunai Y, Tsuburaya R, de la Grange P, Dembele D, Francois V, Precigout G, Boulade-Ladame C, Hummel MC, Lopez de Munain A, Sergeant N, Laquerriere A, Thibault C, Deryckere F, Auboeuf D, Garcia L, Zimmermann P, Udd B, Schoser B, Takahashi MP, Nishino I, Bassez G, Laporte J, Furling D, Charlet-Berguerand N. Misregulated alternative splicing of BIN1 is associated with T tubule alterations and muscle weakness in myotonic dystrophy. Nat Med. 2011 Jun;17(6):720-5. doi: 10.1038/nm.2374. Epub 2011 May 29.
PubMed 21623381Rau F, Laine J, Ramanoudjame L, Ferry A, Arandel L, Delalande O, Jollet A, Dingli F, Lee KY, Peccate C, Lorain S, Kabashi E, Athanasopoulos T, Koo T, Loew D, Swanson MS, Le Rumeur E, Dickson G, Allamand V, Marie J, Furling D. Abnormal splicing switch of DMD's penultimate exon compromises muscle fibre maintenance in myotonic dystrophy. Nat Commun. 2015 May 28;6:7205. doi: 10.1038/ncomms8205.
PubMed 26018658Savkur RS, Philips AV, Cooper TA. Aberrant regulation of insulin receptor alternative splicing is associated with insulin resistance in myotonic dystrophy. Nat Genet. 2001 Sep;29(1):40-7. doi: 10.1038/ng704.
PubMed 11528389Yadava RS, Frenzel-McCardell CD, Yu Q, Srinivasan V, Tucker AL, Puymirat J, Thornton CA, Prall OW, Harvey RP, Mahadevan MS. RNA toxicity in myotonic muscular dystrophy induces NKX2-5 expression. Nat Genet. 2008 Jan;40(1):61-8. doi: 10.1038/ng.2007.28. Epub 2007 Dec 16.
PubMed 18084293
Study at a glance
From the registry record, last updated by the sponsor on 12 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Venous Thromboembolism in Myotonic Dystrophy Type 1
- ClinicalTrials.gov ID
- NCT03424460
- Acronym / sponsor ID
- DM1-VTE / K170601J
- Conditions
- Myotonic Dystrophy 1
- Keywords
- Myotonic dystrophy 1, Venous thromboembolism, Pulmonary embolism, Deep vein thrombosis, Hypercoagulability, Thrombophilia, RNA alternative splicing
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 130 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- AFM-Téléthon (Funding), Recherche Clinique Paris Descartes Necker Cochin Sainte Anne, URC-CIC Paris Descartes Necker Cochin
- Study start
- 11 Jun 2018 (actual)
- Primary completion
- 15 Mar 2023 (actual)
- Study completion
- 15 Mar 2023 (actual)
- First posted
- 7 Feb 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Investigators have identified in the cohort of 1084 patients presenting myotonic dystrophy type 1 (DM1) a 10% prevalence of venous thromboembolism (VTE) and a 7‰ annual incidence, which is 10-fold higher than in the general population and 3-fold compared to patients with other myopathies.
Patients' clinical presentations were very similar to those observed in patients with severe hypercoagulable states caused by mutations in genes encoding factors involved in coagulation, fibrinolysis or their regulation and represented a frequent cause of death.
To Investigator's knowledge, this association between VTE and DM1 has never been reported to date and no competing project has been initiated on this topic by any other team.
Investigators hypothesize that VTE in DM1 may be related to a hypercoagulable state resulting from an imbalance between coagulation processes and fibrinolysis properties. Because the expression of pathogenic CTG repeats in DM1 leads to a RNA gain-of-function mechanism, Investigators propose these abnormalities may be the consequence of alternative splicing misregulation and/or abnormal gene expression of coagulation, fibrinolysis factors or other factors involved in their regulation.
Investigators applied a candidate gene strategy to screen splicing profiles of 33 genes coding for haemostasis factors in a DM1 context. Using expression large-scale datasets of DM1 tissue samples from skeletal muscle and heart, Investigators identified splicing defects in 4 genes involved in haemostasis, in particular 3 involved in the fibrinolytic system: PLAT, PLAU and SERPINE1. These preliminary analyses were however not performed on liver samples whereas genes coding for haemostasis factors are synthesized and mainly expressed in liver. Analysis of liver and monocytes/megacaryotes RNA samples appears to be an essential step.
The objectives are to (i) study haemostatic properties of a cohort of patients with DM1 with and without personal history of VTE, in order to determine whether a hypercoagulable state may be associated with DM1 and whether it may be correlated to the occurrence of VTE, and (ii) to perform a global transcriptomic approach using massive parallel sequencing (RNAseq) on liver and monocytes/megacaryotes. RNA samples obtained from DM1 patients will help identify candidate genes with altered expression or alternative splicing misregulation that may underlie VTE in DM1.
The study will include two complementary parts in DM1 patients with and without personal history of VTE and healthy volunteers: haemostasis tests, and transcriptomic analysis on RNA samples isolated from liver biopsies and blood monocytes/megacaryocytes samples.Three teams will be involved in the study: Team 1 (clinical study), Team 2 (haematology) and Team 3 (transcriptomic analysis).
Haemostasis tests will be performed by Team 1 and analysed by Team 2 in (i) 100 patients prospectively enrolled in Investigator's Institution by Team 1, aged >18 years, with genetically proven DM1, after providing written informed consent, without any current antithrombotic treatment, including 80 without and 20 with personal history of VTE and (ii) 30 healthy volunteers matched on age and sex. RNAseq will be performed on (i) liver tissue issued from 3 patients with DM1 and 6 controls and (ii) monocytes/megacaryocytes isolated from the blood of 15 patients with DM1 (7 with and 8 without VTE) and 15 controls prospectively enrolled in the study. Inclusion and exclusion criteria will be similar to those of patients included in the study of haemostasis properties.
Liver tissues are already available in a tissue bank. Blood will be prospectively collected in DM1 patients and controls by Team 1. Monocytes and megacaryocytes will be isolated and cultured by Team 2.
Team 3 will extract total RNA from liver samples, monocytes and megacaryocytes to the Centre National de Génotypage for RNA sequencing and perform the analysis of the data and the validation of the newly identified candidates.
The estimated study duration is 72 months, including (i) 66 months for patient inclusions, coagulation testsand monocytes/megacaryocytes isolations, and (ii) 6 months for fibrinolysis tests, RNA extraction and sequencing, data analysis, validation.
Investigators believe the study will have important implications for the clinical management of patients with DM1. Specific strategies will be proposed for the prevention of VTE with potentially larger indications for prophylactic anticoagulant treatments and longer duration after a first episode of VTE.
Regarding the high mortality associated with VTE and the identification in the registry of pulmonary embolism as a frequent cause of death, sudden and non-sudden, in DM1 patients, the modification of these treatment strategies may be associated with an important clinical benefit.The identification of haemostasis abnormalities by coagulation and fibrinolysis tests could be useful for risk stratification in patients with DM1 and could allow targeted treatments.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
- Model description
- Two populations: * Population n°1: prospective, with 3 arms * Population n°2: retrospective, with 2 arms
| Arm | Type | Receives |
|---|---|---|
| population 1-A1 : DM1 with VTE | Experimental | Biological: Haemostasis tests, Biological: Monocytes and megacaryocytes culture and RNA extractionMyotonic dystrophy type 1 patients with a history of venous thromboembolism (pulmonary embolism and/or deep vein thrombosis) |
| population 1-B1 : DM1 without VTE | Active comparator | Biological: Haemostasis tests, Biological: Monocytes and megacaryocytes culture and RNA extractionMyotonic dystrophy type 1 patients without a history of venous thromboembolism |
| population 1-C1 : Healthy volunteers | Active comparator | Biological: Haemostasis tests, Biological: Monocytes and megacaryocytes culture and RNA extractionHealthy volunteers without any medical history or treatment |
| population 2-A2 : DM1 liver samples | Experimental | Genetic: RNA extractionLiver samples of patients with myotonic dystrophy type 1 |
| population 2-B2 : Healthy liver samples | Active comparator | Genetic: RNA extractionLiver samples from patients without any medical history |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Population N°1
- Population N°2
Key exclusion criteria (8 listed)
- Patient opposed to data collection and analysis
- 1. Population N°1
- Genetically proven thrombophilia
- Anti-thrombotic medication
- Hemoglobin levels < 7 g/dL
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Haemostasis testsVenipuncture 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 | population 1-A1 : DM1 with VTE, population 1-B1 : DM1 without VTE, population 1-C1 : Healthy volunteers |
| Monocytes and megacaryocytes culture and RNA extractionVenipuncture of 60 milliliters of blood. Monocytes and megacaryocytes culture. RNA extraction from monocytes and megacaryocytes. | Biological | population 1-A1 : DM1 with VTE, population 1-B1 : DM1 without VTE, population 1-C1 : Healthy volunteers |
| RNA extractionRNA extraction from liver tissue | Genetic | population 2-A2 : DM1 liver samples, population 2-B2 : Healthy liver samples |
Primary outcome
Results of thromboelastography in the 3 arms of population n°1
Time frame: 24 months
Results given in thromboelastography traces
7 secondary outcomes
Results of prothrombin time (PT) and activated partial thromboplastin time (APPT) in the 3 arms of population n°1
Time frame: 30 months
Results of plasma fibrinogen levels in the 3 arms of population n°1
Time frame: 24 months
Results of thrombophilia testing in the 3 arms of population n°1
Time frame: 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
Time frame: 24 months
Results of levels of plasmin anti-plasmin complexes
Time frame: 24 months
Results of global test of fibrinolytic activity by the method of von Kaulla
Time frame: 24 months
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: 30 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Sep 2025.
- Background: PubMed 22995693Udd B, Krahe R. The myotonic dystrophies: molecular, clinical, and therapeutic challenges. Lancet Neurol. 2012 Oct;11(10):891-905. doi: 10.1016/S1474-4422(12)70204-1.
- Background: PubMed 2330114Mathieu J, De Braekeleer M, Prevost C. Genealogical reconstruction of myotonic dystrophy in the Saguenay-Lac-Saint-Jean area (Quebec, Canada). Neurology. 1990 May;40(5):839-42. doi: 10.1212/wnl.40.5.839.
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- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Karim Wahbi, MD, PhD principal investigator
Assistance Publique Hôpitaux de Paris (AP-HP)
Denis Duboc, MD, PhD study director
Assistance Publique Hôpitaux de Paris (AP-HP)
Michaela Fontenay, MD, PhD study chair
Assistance Publique Hôpitaux de Paris (AP-HP)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Haemostasis tests, Monocytes and megacaryocytes culture and RNA extraction and RNA extraction in people with Myotonic Dystrophy 1, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Results of thromboelastography in the 3 arms of population n°1 (time frame: 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03424460, which also lists 26 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Sep 2025.