Ignite Creation Date:
2024-05-05 @ 11:38 AM
Last Modification Date:
2024-10-26 @ 9:10 AM
Study NCT ID:
NCT00094185
Status:
COMPLETED
Last Update Posted:
2012-12-20
First Post:
2004-10-15
Brief Title:
Clotting Genetic Variants Hormones and Venous Thrombosis
Sponsor:
University of Washington
Organization:
University of Washington
Study Overview
Official Title:
None
Status:
COMPLETED
Status Verified Date:
2012-12
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:
None
Brief Summary:
To identify genetic variants in 12 key blood clotting proteins that may modify the risk of venous thromboembolism in users of hormone replacement therapy
Detailed Description:
BACKGROUND
Venous thromboembolism VTE occurs commonly in adults and risk increases 3-fold among users of hormone replacement therapy HRT oral contraceptives OC and selective estrogen receptor modulators SERMs Epidemiologic data suggest that genetic variation in the pro-coagulant anti-coagulant and fibrinolytic pathways may modify the risk of VTE in women especially in the presence of hormone use The primary aim of this study is to identify genetic variants in 12 key clotting proteins that may modify the risk of VTE independently through gene-gene interactions and in the presence of HRT OC or SERM use Proteins include thrombomodulin protein C endothelial protein C receptor protein S antithrombin III tissue activatable fibrinolysis inhibitor TAFI tissue plasminogen activator TPA and factors VIII IX X and XlII A and B Secondary aims are to determine if levels of TAFI antigen TPA antigen activated protein C resistance and D-dimer serve as intermediate phenotypes for gene-drug interactions and VTE risk The setting for this study is Group Health Cooperative GHC of Puget Sound a health maintenance organization in the Pacific Northwest This study is part of an on going case-control study addressing the effects of genetic variants on drug safety particularly cardiovascular endpoints
DESIGN NARRATIVE
The primary aim of this case-control study is to identify genetic variants in 12 key blood clotting proteins that may modify the risk of venous thromboembolism independently through gene-gene interactions and in the presence of hormone replacement therapy oral contraceptives or selective estrogen receptor modulators use Proteins include thrombomodulin protein C endothelial protein C receptor protein S antithrombin III tissue activatable fibrinolysis inhibitor TAFI tissue plasminogen activator TPA and factors VIII IX X and XlII A and B Secondary aims of the study are to determine if levels of TAFI antigen TPA antigen activated protein C resistance and D-dimer serve as intermediate phenotypes for gene-drug interactions and VTE risk The setting for this study is the Group Health Cooperative GHC of Puget Sound a health maintenance organization in the Pacific Northwest This study is part of an on going case-control study addressing the effects of genetic variants on drug safety particularly cardiovascular endpoints
All inpatient and outpatient VTE events occurring between 111995 and 12312007 among women 18 to 89 years of age will be eligible for this study Controls will be a random selection of women from GHC matched on age hypertension status and calendar year Medical records will be reviewed to determine study eligibility and to collect ViE risk factor information Hormone and SERM use will be ascertained from the GHC pharmacy database Phlebotomy will be performed on surviving cases and controls to collect plasma samples and genetic information Logistic regression analyses will determine which haplotypes of key elements in the clotting pathways modify the association between hormones or SERMSs and VTE risk The identification of common genetic variants that either increase or decrease VTE risk independently or in the presence of hormone or SERMs will help to inform clinicians and their female patients about the personal safety of hormone use
The Seattle Program for Genomics Applications PGA will identify single nucleotide polymorphisms SNPs in the 12 candidate genes and use linkage disequilibrium to generate haplotypes A group at the Leiden University Medical Center will perform the genotyping of the study population
Venous thromboembolism VTE occurs commonly in adults and risk increases 3-fold among users of hormone replacement therapy HRT oral contraceptives OC and selective estrogen receptor modulators SERMs Epidemiologic data suggest that genetic variation in the pro-coagulant anti-coagulant and fibrinolytic pathways may modify the risk of VTE in women especially in the presence of hormone use The primary aim of this study is to identify genetic variants in 12 key clotting proteins that may modify the risk of VTE independently through gene-gene interactions and in the presence of HRT OC or SERM use Proteins include thrombomodulin protein C endothelial protein C receptor protein S antithrombin III tissue activatable fibrinolysis inhibitor TAFI tissue plasminogen activator TPA and factors VIII IX X and XlII A and B Secondary aims are to determine if levels of TAFI antigen TPA antigen activated protein C resistance and D-dimer serve as intermediate phenotypes for gene-drug interactions and VTE risk The setting for this study is Group Health Cooperative GHC of Puget Sound a health maintenance organization in the Pacific Northwest This study is part of an on going case-control study addressing the effects of genetic variants on drug safety particularly cardiovascular endpoints
DESIGN NARRATIVE
The primary aim of this case-control study is to identify genetic variants in 12 key blood clotting proteins that may modify the risk of venous thromboembolism independently through gene-gene interactions and in the presence of hormone replacement therapy oral contraceptives or selective estrogen receptor modulators use Proteins include thrombomodulin protein C endothelial protein C receptor protein S antithrombin III tissue activatable fibrinolysis inhibitor TAFI tissue plasminogen activator TPA and factors VIII IX X and XlII A and B Secondary aims of the study are to determine if levels of TAFI antigen TPA antigen activated protein C resistance and D-dimer serve as intermediate phenotypes for gene-drug interactions and VTE risk The setting for this study is the Group Health Cooperative GHC of Puget Sound a health maintenance organization in the Pacific Northwest This study is part of an on going case-control study addressing the effects of genetic variants on drug safety particularly cardiovascular endpoints
All inpatient and outpatient VTE events occurring between 111995 and 12312007 among women 18 to 89 years of age will be eligible for this study Controls will be a random selection of women from GHC matched on age hypertension status and calendar year Medical records will be reviewed to determine study eligibility and to collect ViE risk factor information Hormone and SERM use will be ascertained from the GHC pharmacy database Phlebotomy will be performed on surviving cases and controls to collect plasma samples and genetic information Logistic regression analyses will determine which haplotypes of key elements in the clotting pathways modify the association between hormones or SERMSs and VTE risk The identification of common genetic variants that either increase or decrease VTE risk independently or in the presence of hormone or SERMs will help to inform clinicians and their female patients about the personal safety of hormone use
The Seattle Program for Genomics Applications PGA will identify single nucleotide polymorphisms SNPs in the 12 candidate genes and use linkage disequilibrium to generate haplotypes A group at the Leiden University Medical Center will perform the genotyping of the study population
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
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 |
|---|---|---|---|
| R01HL073410-01 | NIH | None | httpsreporternihgovquickSearchR01HL073410-01 |