Clinical trial NCT00344435: Genetic Susceptibility to Factor VIII Inhibitors
Official title: Factor VIII Inhibitor Formation: Identifying Predisposing Genetic Factors
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Hemophilia
Keywords: Hemophilia
Antibody
Mutations
SNP
clotting
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
First posted: 2006-06-26
Enrollment: 1187
Sex: ALL
Minimum age (years): 1
Maximum age (years): 100
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: FAMILY_BASED
Time perspective: CROSS_SECTIONAL

Brief summary: This international study will identify genetic factors that may influence the development of inhibitory antibodies in patients with hemophilia A after treatment with factor VIII. Bleeding episodes in patients with inhibitors are often more difficult to treat. Previous research indicates that genetic factors play a role in the development of inhibitors. A better understanding of the influence of genes in this treatment complication may be helpful in predicting, treating or preventing inhibitors.

People in families in which one or more members have severe factor VIII deficiency and one or more have a history of an inhibitor may be eligible for this study. Participants fill out a form with questions about the person's relationship to other family members taking part in the study. Those with hemophilia provide a brief medical history, including hemophilia-related information, inhibitor history and the presence of other conditions such as hepatitis C and HIV. All participants have a blood sample taken for laboratory and research tests.

Detailed description: In collaboration with investigators of the Hemophilia Inhibitor Genetic Study (HIGS) multicenter study and the University of Lund, University Hospital, Malmo, Sweden, we propose to assess the role of genetic variants in the process of developing inhibitors to Factor VIII in persons with hemophilia. The discovery of genetic associations offers the potential to direct clinical management in order to prevent inhibitor development and improve clinical care in patients with inhibitors.

Eligibility criteria: * INCLUSION CRITERIA

DNA and relevant clinical data from properly consented hemophiliac subjects and family members (maximum estimated = 3500) will be provided to the LGD for genotyping and analysis.

EXCLUSION CRITERIA

No available subjects will be excluded to maximize power.

Primary outcomes:
measure: Collection from 3500 donors
timeFrame: Every six months
Secondary outcomes:
Other outcomes:
Locations:
city: Malmo
country: Sweden
facility: University Hospital, University of Lund
Study officials:
affiliation: National Cancer Institute (NCI)
name: Janelle Cortner, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Vermylen J. How do some haemophiliacs develop inhibitors? Haemophilia. 1998 Jul;4(4):538-42. doi: 10.1046/j.1365-2516.1998.440538.x.
citation: Frommel D, Allain JP. Genetic predisposition to develop factor VIII antibody in classic hemophilia. Clin Immunol Immunopathol. 1977 Jul;8(1):34-8. doi: 10.1016/0090-1229(77)90089-7. No abstract available.
citation: Astermark J, Berntorp E, White GC, Kroner BL; MIBS Study Group. The Malmo International Brother Study (MIBS): further support for genetic predisposition to inhibitor development in hemophilia patients. Haemophilia. 2001 May;7(3):267-72. doi: 10.1046/j.1365-2516.2001.00510.x.