FIA
Familial Intracranial Aneurysm Study (Phase I)
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Status:
Phase I is active for follow-up only. Phase I completed in 2009 and Phase II started.
Purpose:
To identify possible genes that may increase the risk of stroke and particularly the development of aneurysms in blood vessels of the brain.
Location(s):
US, Canada, New Zealand, Australia
Year Started:
2002
Year Finished:
2009
Year Presented:
2010
Design:
Multicenter, retrospective and prospective, genome-wide linkage study.
Inclusion Criteria
Two or more affected pairs of siblings (brothers/sisters) or 3 or more family members affected with intracerebral aneurysms. Eligible families include: 1) Families with at least 2 living affected siblings, 2) Families with at least 2 affected siblings, one is living and the other whose genotype can be reconstructed, 3) Families with ≥ 3 affected non-sibling family members, two of whom both alive and have living connecting relatives, and 4) Families with > 3 affected, with one living and at least one other affected relative whose genotype can be reconstructed.
Exclusion Criteria
History of polycystic kidney disease, Marfan’s Syndrome, Ehler Danlos Syndrome, or fibromuscular dyslpasia.
Patient Involvement:
Participants will be asked to complete a family history questionnaire and a medical history questionnaire. They will also have their blood pressure measured and will give a small sample of blood. In addition, certain family members will be offered the opportunity to undergo a Magnetic Resonance Angiography MRA (a non-invasive diagnostic test) to look for undiagnosed brain aneurysms.
Additionally, participants will be contacted by mail on a yearly basis to evaluate their health, and to determine if any other family members have developed intracranial aneurysms.
Primary Outcome:
SNP genotyping; nonparametric (allele sharing) linkage analysis, including environmental risk factors is conducted; and fine gene mapping will be performed.
Results:
Of the 2,794 subjects enrolled, 1,073 had a diagnosis of IA at the time of study entry, and 1,721 had no diagnosis of IA. There were 8,495 person-years of follow-up, with the overall mean follow-up time of 3.04+/-1.73 years. There was no significant difference (p=.12) in the length of follow-up between the affected IA (3.11+/-1.68 years) and unaffected (3.00+/-1.76) groups. Age at study entry for affecteds (54.811.7 years) was significantly (p.0001) older than for
unaffecteds (48.625.9). A Cox proportional hazards model was utilized taking into account age, race, gender, affected status, rupture status, smoking history, and hypertension. After adjusting for age, the overall mortality rate for affecteds was not significantly different than unaffecteds. However, in affected subjects under the age of 55, the risk of death was 4.3 times that of unaffected subjects in the same age group (95% CI 1.58-11.7, p.004). The annual
mortality rate was 13.2 per 1000 for affecteds and 8.5 per 1000 for unaffecteds. In conclusion, all but one of the deaths attributed to ruptured IA occurred shortly after study entry due to the initial rupture, yet the overall causes of death in this high-risk cohort during follow-up were more commonly unrelated to their aneurysms. None of the 1721 family members without known IA at study onset died from a subsequent ruptured IA.
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Source of Information:
Direct correspondence with trial coordinators.
ClinicalTrials.gov
Presented at the 30th International Stroke Conference [February 2005].
Presented at the 2006 International Stroke Conference [February 2006].
Presented at the 2007 International Stroke Conference [February 2007].
Presented at the 2010 International Stroke Conference [February 2010].
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Web Links and Publications:
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This information last updated on: 6/25/2010
Reviewed on: 06/22/2010.
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