Hemophilia Inhibitor Genetics Study (HIGS)

NCT00166387 | Completed DMC

• 1 other identifier: HIGS
• Study Type: observational
• Target: 1,137
• Locations: 1 country
• Sites: 1

Brief Summary

Several non-genetic and genetic factors that could influence the risk of inhibitor development in hemophilia A have been discussed but not fully explored. The aim of the HIGS is to identify these genetic factors.

Conditions

Hemophilia A With Inhibitor

Keywords

Hemophilia; Inhibitors

Outcome Measures

Primary Outcomes (1)

• development of inhibitory antibodies to factor VIII

  upon development of inhibitor or following at least 100 exposure days to factor VIII

Study Arms (1)

Phase I, II, III

Phase I consists of a brother pair with hemophilia, one or both of whom has a history of inhibitors, and their parents; Phase II consists of a person with hemophilia and an inhibitor, and both his parents; Phase III consists of an unrelated group of people with hemophilia.

Procedure: Blood draw

Interventions

Blood draw PROCEDURE

A single blood draw.

Also known as: N/A to this study.

Phase I, II, III

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

People with hemophilia and their parents.

You may qualify if:

• Severe hemophilia A is defined as a baseline factor VIII level \<1%. A history of inhibitor is defined as ever having a Bethesda titer \> 1 BU.
• Phase I.
• Subjects with hemophilia are eligible for Phase I of the study if all of the following apply:
• An informed consent form, approved by the appropriate IRB/IEC, has been administered, signed, and dated.
• The subject has severe hemophilia A.
• The subject has a history of inhibitor or the subject has no history of inhibitor but has at least 100 exposure days to factor VIII products.
• Sufficient documentation exists to identify the subject's maximum lifetime Bethesda titer.
• The subject has a history of inhibitor and has one or more full brothers with severe hemophilia A, with or without an inhibitor, who are eligible for and have agreed to be in the study, and two parents who have agreed to be in the study or the subject does not have a history of inhibitor but has one or more full brothers with severe hemophilia A and a history of inhibitor who are eligible for and have agreed to be in the study, and two parents who have agreed to be in the study.
• Subjects without hemophilia are eligible for Phase I of the study if all of the following apply:
• An informed consent form, approved by the appropriate IRB/IEC, has been administered, signed, and dated.
• The subject is the parent (mother or father) of, or the full sibling of, a subject with hemophilia who is eligible for Phase I of the study.
• Phase II.
• Subjects with hemophilia are eligible for Phase II of the study if all of the following apply:
• An informed consent form, approved by the appropriate IRB/IEC, has been administered, signed, and dated.
• The subject has severe hemophilia A.

You may not qualify if:

• Phase I.
• Subjects (with or without hemophilia) are excluded from participation in Phase I if:
• The minimum family group, defined as a pair of full brothers with hemophilia, either concordant (both with) or discordant (one with, one without) for inhibitor, and both of their parents, is not enrolled.
• Phase II.
• Subjects are excluded from participation in Phase II if:
• The minimum family group, defined as a person with hemophilia and a history of inhibitor and his mother and father, is not enrolled.

Sponsors & Collaborators

• Skane University Hospital: lead

Study Sites (1)

Malmo University Hospital

Malmo, SE-205 02, Sweden

Location

Related Publications (3)

• Berntorp E, Astermark J, Donfield SM, Nelson GW, Oldenburg J, Shapiro AD, Dimichele DM, Ewenstein BM, Gomperts ED, Winkler CA; Hemophilia Inhibitor Genetics Study. Haemophilia Inhibitor Genetics Study - evaluation of a model for studies of complex diseases using linkage and association methods. Haemophilia. 2005 Jul;11(4):427-9. doi: 10.1111/j.1365-2516.2005.01119.x. No abstract available.

  PMID: 16011603 BACKGROUND

• Astermark J, Donfield SM, Gomperts ED, Schwarz J, Menius ED, Pavlova A, Oldenburg J, Kessing B, DiMichele DM, Shapiro AD, Winkler CA, Berntorp E; Hemophilia Inhibitor Genetics Study (HIGS) Combined Cohort. The polygenic nature of inhibitors in hemophilia A: results from the Hemophilia Inhibitor Genetics Study (HIGS) Combined Cohort. Blood. 2013 Feb 21;121(8):1446-54. doi: 10.1182/blood-2012-06-434803. Epub 2012 Dec 6.

  PMID: 23223434 BACKGROUND

• Schwarz J, Astermark J, Menius ED, Carrington M, Donfield SM, Gomperts ED, Nelson GW, Oldenburg J, Pavlova A, Shapiro AD, Winkler CA, Berntorp E; Hemophilia Inhibitor Genetics Study Combined Cohort. F8 haplotype and inhibitor risk: results from the Hemophilia Inhibitor Genetics Study (HIGS) Combined Cohort. Haemophilia. 2013 Jan;19(1):113-8. doi: 10.1111/hae.12004. Epub 2012 Sep 7.

  PMID: 22958194 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Plasma, cells, DNA

MeSH Terms

Conditions

Hemophilia A

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Erik Berntorp, MD, PhD

  Skane University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: FAMILY BASED
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor Erik Berntorp, Malmö University Hospital

Study Record Dates

• First Submitted: September 9, 2005
• First Posted: September 14, 2005
• Study Start: April 1, 2003
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2013
• Last Updated: March 26, 2014

Record last verified: 2014-03

Locations

SE (1)