Hemophilia A With InhibitorNCT00166387
Hemophilia Inhibitor Genetics Study (HIGS)
An observational study of Hemophilia A With Inhibitor, run by Skane University Hospital at 1 site in Sweden.
Trial 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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Hemophilia A With Inhibitor
- What is being tested?
- Blood draw
- Type of treatment
- Surgery or procedure
- How many people
- 1,137 participants
- Where
- 1 siteSweden
- Study dates
- Apr 2003to Dec 2013
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: People with hemophilia and their parents.
Who may be able to join
- 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.
Show all 20Show fewer
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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.
- Conditions
- Hemophilia A With Inhibitor
- Being tested
- Blood draw
- Keywords
- Hemophilia, Inhibitors
- Medical subject headings
- Hemophilia A
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Blood drawProcedure or surgery
Also called N/A to this study.
A single blood draw.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Procedure: Blood draw |
What is being measured
The primary outcome is the main question the study is designed to answer.
development of inhibitory antibodies to factor VIII
Measured: upon development of inhibitor or following at least 100 exposure days to factor VIII
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Sep 2005 (estimated)
- Study startApr 2003
- Primary completionDec 2013
- Study completionDec 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Hemophilia A With InhibitorStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Family based
- Enrolment
- 1,137 participants (actual)
Sponsor and investigators
- Lead sponsor
- Skane University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Sharyne M. Donfield, Ph.D., Skane University Hospital
- Investigators
- Erik Berntorp, MD, PhD, Principal investigator, Skane University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00166387
- Sponsor's protocol ID
- HIGS
- Status last verified
- Mar 2014
- First submitted
- 9 Sep 2005
- Last updated
- 26 Mar 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 16011603Astermark 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.
PubMed 23223434Schwarz 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.
PubMed 22958194
Study at a glance
From the registry record, last updated by the sponsor on 26 Mar 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hemophilia Inhibitor Genetics Study (HIGS)
- ClinicalTrials.gov ID
- NCT00166387
- Acronym / sponsor ID
- HIGS
- Conditions
- Hemophilia A With Inhibitor
- Keywords
- Hemophilia, Inhibitors
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 1,137 participants (actual)
- Lead sponsor
- Skane University HospitalUniversity, hospital or other
- Study start
- Apr 2003
- Primary completion
- Dec 2013 (actual)
- Study completion
- Dec 2013 (actual)
- First posted
- 14 Sep 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Observational model
- Family based
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Phase I, II, III | – | Procedure: Blood drawPhase 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. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- People with hemophilia and their parents.
Key inclusion criteria (20 listed)
- 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.
Key exclusion criteria (6 listed)
- Phase I.
- 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.
- The minimum family group, defined as a person with hemophilia and a history of inhibitor and his mother and father, is not enrolled.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Blood drawAlso: N/A to this study.A single blood draw. | Procedure or surgery | Phase I, II, III |
Primary outcome
development of inhibitory antibodies to factor VIII
Time frame: upon development of inhibitor or following at least 100 exposure days to factor VIII
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Mar 2014.
- Background: PubMed 16011603Berntorp 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.
- Background: PubMed 23223434Astermark 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.
- Background: PubMed 22958194Schwarz 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Erik Berntorp, MD, PhD principal investigator
Skane University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hemophilia A With Inhibitor, run by Skane University Hospital at 1 site in Sweden.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Mar 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
development of inhibitory antibodies to factor VIII (time frame: upon development of inhibitor or following at least 100 exposure days to factor VIII). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00166387, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Mar 2014.