Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT00094185 |
| Other study ID # |
1277 |
| Secondary ID |
R01HL073410-01 |
| Status |
Completed |
| Phase |
N/A
|
| First received |
October 15, 2004 |
| Last updated |
December 18, 2012 |
| Start date |
May 2004 |
| Est. completion date |
March 2009 |
Study information
| Verified date |
December 2012 |
| Source |
University of Washington |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
United States: Federal Government |
| Study type |
Observational
|
Clinical Trial 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.
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 1/1/1995 and 12/31/2007 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 V'i'E 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.
