Genomics of Fibrin Clot Structure in Patients With Constitutional Dysfibrinogenemia (GENDYSFIB)
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ClinicalTrials.gov Identifier: NCT05233384 |
Recruitment Status :
Recruiting
First Posted : February 10, 2022
Last Update Posted : October 12, 2022
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Tracking Information | |||||
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First Submitted Date | January 6, 2022 | ||||
First Posted Date | February 10, 2022 | ||||
Last Update Posted Date | October 12, 2022 | ||||
Actual Study Start Date | July 28, 2022 | ||||
Estimated Primary Completion Date | January 2024 (Final data collection date for primary outcome measure) | ||||
Current Primary Outcome Measures |
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
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Original Primary Outcome Measures | Same as current | ||||
Change History | |||||
Current Secondary Outcome Measures |
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Original Secondary Outcome Measures | Same as current | ||||
Current Other Pre-specified Outcome Measures | Not Provided | ||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||
Descriptive Information | |||||
Brief Title | Genomics of Fibrin Clot Structure in Patients With Constitutional Dysfibrinogenemia | ||||
Official Title | Genomics of Fibrin Clot Structure in Patients With Constitutional Dysfibrinogenemia | ||||
Brief Summary | 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. |
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Detailed Description | Not Provided | ||||
Study Type | Observational | ||||
Study Design | Observational Model: Cohort Time Perspective: Cross-Sectional |
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Target Follow-Up Duration | Not Provided | ||||
Biospecimen | Not Provided | ||||
Sampling Method | Probability Sample | ||||
Study Population | Patient with confirmed hereditary dysfibrinogenemia | ||||
Condition | Hereditary Dysfibrinogenemia | ||||
Intervention | 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).
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Study Groups/Cohorts | Patients with hereditary dysfibrinogenemia
Patient, male or female, aged over 18, with confirmed hereditary dysfibrinogenemia
Intervention: Biological: Blood test
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Publications * | Not Provided | ||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||
Recruitment Status | Recruiting | ||||
Estimated Enrollment |
50 | ||||
Original Estimated Enrollment | Same as current | ||||
Estimated Study Completion Date | June 2024 | ||||
Estimated Primary Completion Date | January 2024 (Final data collection date for primary outcome measure) | ||||
Eligibility Criteria | Inclusion Criteria:
Exclusion Criteria:
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Sex/Gender |
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Ages | 18 Years and older (Adult, Older Adult) | ||||
Accepts Healthy Volunteers | No | ||||
Contacts |
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Listed Location Countries | France | ||||
Removed Location Countries | |||||
Administrative Information | |||||
NCT Number | NCT05233384 | ||||
Other Study ID Numbers | RNI 2021 LEBRETON 2021-A00745-36 ( Other Identifier: 2021-A00745-36 ) |
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Has Data Monitoring Committee | No | ||||
U.S. FDA-regulated Product |
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IPD Sharing Statement | Not Provided | ||||
Current Responsible Party | University Hospital, Clermont-Ferrand | ||||
Original Responsible Party | Same as current | ||||
Current Study Sponsor | University Hospital, Clermont-Ferrand | ||||
Original Study Sponsor | Same as current | ||||
Collaborators | Not Provided | ||||
Investigators |
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PRS Account | University Hospital, Clermont-Ferrand | ||||
Verification Date | July 2022 |