Ignite Creation Date:
2024-05-06 @ 5:13 PM
Last Modification Date:
2024-10-26 @ 2:24 PM
Study NCT ID:
NCT05233384
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2024-06-18
First Post:
2022-01-06
Brief Title:
Genomics of Fibrin Clot Structure in Patients With Constitutional Dysfibrinogenemia
Sponsor:
University Hospital Clermont-Ferrand
Organization:
University Hospital Clermont-Ferrand
Study Overview
Official Title:
Genomics of Fibrin Clot Structure in Patients With Constitutional Dysfibrinogenemia
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2024-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
GENDYSFIB
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 patients 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 patients 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
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 patients 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 patients 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
Detailed Description:
None
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 2021-A00745-36 | OTHER | 2021-A00745-36 | None |