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Hemophilia Inhibitor Genetics Study (HIGS)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Sharyne M. Donfield, Ph.D., Skane University Hospital
ClinicalTrials.gov Identifier:
NCT00166387
First received: September 9, 2005
Last updated: April 18, 2012
Last verified: April 2012
History of Changes
  Purpose

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.


Condition Intervention
Hemophilia A With Inhibitor
 Procedure: Blood draw

Study Type: Observational
Study Design: Observational Model: Family-Based
Official Title: Hemophilia Inhibitor Genetics Study (HIGS)

Resource links provided by NLM:

MedlinePlus related topics: Hemophilia
U.S. FDA Resources

Further study details as provided by Skane University Hospital:

Primary Outcome Measures:
  • development of inhibitory antibodies to factor VIII [ Time Frame: upon development of inhibitor or following at least 100 exposure days to factor VIII ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

Plasma, cells, DNA


Estimated Enrollment: 1025
Study Start Date: April 2003
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
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
A single blood draw.
Other Name: N/A to this study.

Detailed Description:

The objective of the HIGS is to determine host genetic factors, other than mutations within the factor VIII gene, that are associated with the development of inhibitors in severe hemophilia A and response to antigenic challenge by factor VIII. The study will involve three phases, enrolling family groups composed of brother pairs and their parents (Phase I) and siblings, a family group composed of a person with severe hemophilia and his parents (Phase II), and a group of unrelated people with severe hemophilia for the purpose of confirming associations identified in Phases I and II.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

People with hemophilia and their parents.

Criteria

Inclusion Criteria:

  • 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.
  • The subject has a history of inhibitor and two parents who have agreed to be in the study.
  • Sufficient documentation exists to identify the subject's maximum lifetime Bethesda titer.

Subjects without 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 is the parent (mother or father) of a subject with hemophilia who is eligible for Phase II of the study.

Exclusion Criteria:

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00166387

Locations
Sweden
Malmo University Hospital
Malmo, Sweden, SE-205 02
Sponsors and Collaborators
Skane University Hospital
Investigators
Principal Investigator: Erik Berntorp, MD, PhD Malmo University Hospital
  More Information

Publications:

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Sharyne M. Donfield, Ph.D., Professor Erik Berntorp, Malmö University Hospital, Skane University Hospital
ClinicalTrials.gov Identifier: NCT00166387     History of Changes
Other Study ID Numbers: HIGS
Study First Received: September 9, 2005
Last Updated: April 18, 2012
Health Authority: Sweden: Medical Products Agency

Keywords provided by Skane University Hospital:
Hemophilia
Inhibitors

Additional relevant MeSH terms:
Hemophilia A
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
 Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn

ClinicalTrials.gov processed this record on May 21, 2013