Genomics of Fibrin Clot Structure in Patients With Constitutional Dysfibrinogenemia (GENDYSFIB)
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| ClinicalTrials.gov Identifier: NCT05233384 |
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Recruitment Status :
Recruiting
First Posted : February 10, 2022
Last Update Posted : October 12, 2022
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Hereditary dysfibrinogenemia results from monoallelic mutation in one of the fibrinogen genes (FGA, FGB, FGG). The spectrum of molecular abnormalities is broad, leading to several subtypes of coagulation disorders with specific biological and clinical features. The correlation between the genotype and the phenotype is poor, and the clinical course of patients, from major bleeding to recurrent thromboses, is unpredictable. Fibrin clot structure is a determinant of the risk of thrombosis in cardiovascular diseases. In all individuals, fibrin networks define the propensity of clot to be more resistant to removal or, on the contrary, susceptible to fragmentation leading to bleeding complications. Besides fibrinogen variants, other relatively common genetic polymorphisms in coagulation and fibrinolytic pathways may affect the fibrin clot structure and therefore act as modifiers of the blood clot function.
In this proposal, the investigators will analyze properties (polymerization, fibrinolysis, viscoelastic properties, permeation) and ultrastructure (size, number, packaging, architecture of fibrin fiber by confocal microscopy and scanning electron microscopy) of plasma-based clots in relation to the presence of genetic modifiers (polymorphisms). Polymorphisms will be detected using a whole exome sequencing (WES) in a selected panel of genes of the coagulation and fibrinolytic pathways. The gene panel of 28 genes will include the three fibrinogen genes plus 25 potential modifier genes including F5, F2, PAI-1, PROCR and MTHFR. The overall clot phenotype will be correlated to the presence of prothrombotic polymorphisms and to the patient's clinical phenotype. The investigators plan to include about 100 patients with dysfibrinogenemia. The combination of integrative hemostasis models with genetic dataset will provide a global view of the patient's individual hemostatic profile. This may allow to better predict the clinical outcome and help provide a more personalized therapeutic strategy and precision medicine. In addition, the development of models allowing a reliable global assessment of fibrin clot architecture will be the basis for further research in other acquired diseases involving thrombotic or bleeding events.
| Condition or disease | Intervention/treatment |
|---|---|
| Hereditary Dysfibrinogenemia | Biological: Blood test |
| Study Type : | Observational |
| Estimated Enrollment : | 50 participants |
| Observational Model: | Cohort |
| Time Perspective: | Cross-Sectional |
| Official Title: | Genomics of Fibrin Clot Structure in Patients With Constitutional Dysfibrinogenemia |
| Actual Study Start Date : | July 28, 2022 |
| Estimated Primary Completion Date : | January 2024 |
| Estimated Study Completion Date : | June 2024 |
| Group/Cohort | Intervention/treatment |
|---|---|
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Patients with hereditary dysfibrinogenemia
Patient, male or female, aged over 18, with confirmed hereditary dysfibrinogenemia
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Biological: Blood test
For each patient included, this study will involve the collection of 20 ml of blood during a blood test carried out as part of routine care. One EDTA tube (4,5 ml) will be withdrawn and frozen for genetic testing. 15 ml of citrated blood sample (3 to 5 tubes, depending on the used tubes) are necessary for the study of fibrin clot structure. Citrated tubes will be double centrifugated and frozen (-80°C) according to Groupe Français d'Études sur l'Hémostase et la thrombose guidelines (centrifugation protocol: 1500 to 2000g at least 15min, or 2000 to 2500g at least 10min with an intermediate decantation). |
- relation between the genetic polymorphisms and the main parameters of each different tools evaluating the ultrastructure of fibrin clot [ Time Frame: at the end of the inclusion periode ]High quality genomic DNA will be purified using standard procedures and quantified using the Thermo Fisher Qubit fluorometric quantification. Whole exome sequencing will be performed at the Health 2030 Genome Center, Campus Biotech, Geneva using IDT Research Exome Reagents, multiplexing 12 samples during library preparation, for a mean coverage of 70x
- relation between the genetic polymorphisms and the clinical phenotype of patients with dysfibrinogenemia (thrombotic and/or bleeding phenotype) [ Time Frame: at the end of the inclusion periode ]
- relation between the main parameters of ultrastructure of fibrin clot properties and the clinical phenotype of patients with dysfibrinogenemia [ Time Frame: at the end of the inclusion periode ]
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
| Sampling Method: | Probability Sample |
Inclusion Criteria:
- Patient with confirmed hereditary dysfibrinogenemia
- Able to give his/her informed consent to participate
- Affiliated to the French Health insurance
Exclusion Criteria:
- Refusal to participate
- pregnant and breastfeeding women,
- protected adults (individuals under guardianship by court order),
- adults deprived of their liberty
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): NCT05233384
| Contact: Lise Laclautre | 334.73.754.963 | promo_interne_drci@chu-clermontferrand.fr |
| France | |
| CHU clermont-ferrand | Recruiting |
| Clermont-Ferrand, France | |
| Contact: Lise Laclautre | |
| Principal Investigator: Aurélien LEBRETON | |
| CHU Dijon | Recruiting |
| Dijon, France | |
| Contact: Lise Laclautre | |
| Principal Investigator: Emmanuel DE MAISTRE | |
| CHU de Lille | Not yet recruiting |
| Lille, France | |
| Contact: lise Laclautre | |
| Principal Investigator: Nathalie Trillot | |
| CHU Montpellier | Not yet recruiting |
| Montpellier, France | |
| Contact: Lise Laclautre | |
| Principal Investigator: Christine BIRON ANDREANI | |
| CHu Nancy | Not yet recruiting |
| Nancy, France | |
| Contact: Lise Laclautre | |
| Principal Investigator: Birgit FROTSCHER | |
| CHU Nantes | Not yet recruiting |
| Nantes, France | |
| Contact: Lise Laclautre | |
| Principal Investigator: Nicolas DRILLAUD | |
| CHU Tours | Not yet recruiting |
| Tours, France | |
| Contact: Lise Laclautre | |
| Principal Investigator: Laurent ARDILLON | |
| Principal Investigator: | Aurélien LEBRETON | University Hospital, Clermont-Ferrand |
| Responsible Party: | University Hospital, Clermont-Ferrand |
| ClinicalTrials.gov Identifier: | NCT05233384 |
| Other Study ID Numbers: |
RNI 2021 LEBRETON 2021-A00745-36 ( Other Identifier: 2021-A00745-36 ) |
| First Posted: | February 10, 2022 Key Record Dates |
| Last Update Posted: | October 12, 2022 |
| Last Verified: | July 2022 |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
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Hereditary Dysfibrinogenemia Fibrin clot Polymorphism |