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Intracranial AneurysmGAÏANCT02848495

Biocollection on the Familial Forms of Intracranial Aneurysm

An observational study of Intracranial Aneurysm, run by Nantes University Hospital at 8 sites in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Intracranial aneurysm (IA) is an asymptomatic cerebrovascular abnormality affecting 3.2% of the general population. The devastating complication of IA is its rupture, resulting in subarachnoid haemorrhage that can lead to severe disability and death. Read more about this study

Who is it for?
Ages 20 years and older
Conditions the study is for
Intracranial Aneurysm
What is being tested?
Non-Interventional
How many people
411 participants
Where
8 sitesFrance
Study dates
Jan 2013to Jan 2017
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 20 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Study population: The initial stage of this biocollection based on the recruitment of large families for genetic linkage analysis. In the first instance, we identify patients with intracranial aneurysms occurring in a family context, and to conduct a comprehensive investigation according to clinical guidelines in force to assess the potentially informative family and ensure their adherence to the prior biocollection. The next step consists on the fine and accurate phenotyping of each of the family members (imaging) and the collection of a blood sample for DNA extraction for molecular genetic analysis. The population recruited will be composed of index and their healthy relatives and cases with sporadic cases and IA. The kinship links will be established from family trees.

Who may be able to join

  • Inclusion criteria indexes and related cases (familial) of intracranial aneurysms:
  • Index: Any patient consulting for a major IA and some typical bifurcation with at least one other case reached akin IA 1st degree
  • Related: All similar to the first degree, aged 20 or more, patients with a family background of IA and some typical bifurcation (≥2 achieved) For the latter, directed by screening with Magnetic resonance imaging (MRI) sequence Time of Flight (TOF), axial T2, EGT2.
  • Consent oral and in writing to the Biocollection consent Form for participation in the collection of biological samples
  • Any patient consulting for IA and some typical bifurcation
  • Patients aged of 20 years or older
  • Consent oral and in writing to the Biocollection consent Form for participation in the collection of biological samples

Who cannot join

  • Non Inclusion Criteria:
  • Patients who have shown the inability or have refused to sign the consent informed biocollection
  • Syndromic diagnosis known as IA provider
  • Marfan Syndrome
  • AOS with SMAD 3
  • Danlos Syndrome Elhers type II and IV
Show all 15Show fewer
  • Autosomal Dominant Polycystic
  • Moyamoya Syndrome
  • Character of IA:
  • Dissecting or fusiform
  • Combined with an arteriovenous malformation
  • Blister-like
  • Mycotic
  • Pathology of the cerebral white matter detected on MRI, evoking:
  • COL4A1 mutation

Trial locations and contacts

8 sites in 1 country.

8 sites in 1 country

France8 sites

  • AP-HP, Henri Mondor hospital

    Créteil, 94000

  • CHD La Roche sur YON

    La Roche-sur-Yon, 85925

  • Nantes University Hospital

    Nantes, 44093

  • University Hospital Poitiers

    Poitiers, 86021

  • University Hospital Rennes

    Rennes, 35033

  • Rouen University Hospital

    Rouen, 76031

  • Bordeaux University Hospital

    Talence, 33404

  • Tours University Hospital

    Tours, 37044

Other trials in France

About this study

Official title: Genetic Study on the Familial Forms of Intracranial Aneurysm

Intracranial aneurysm (IA) is an asymptomatic cerebrovascular abnormality affecting 3.2% of the general population. The devastating complication of IA is its rupture, resulting in subarachnoid haemorrhage that can lead to severe disability and death.

Unfortunately, there are neither reliable clues nor diagnostic tools to predict the formation and/or the fate of an IA in a given individual. Also, there is no pharmacological drug available to prevent the rupture of aneurysm and subsequent subarachnoid haemorrhage. Current treatments are invasive with a significant risk of procedural morbidity. Thus, still now, the management of patients with IA remains extremely challenging and still controversial.

Read more

Although the pathogenesis of IA has been the subject of many studies for the last decade, the mechanisms underlying IA formation, growth and rupture are still mostly unknown and relevant animal models of IA are not available.

Familial history of IA predisposes to IA formation and rupture and increasing evidence suggest a genetic component of IA formation, with heterogeneous modes of inheritance and penetrance.

This project, gathering neuroradiologists, geneticists and vascular biologists, addresses the urgent need to understand the pathogenic mechanisms of IA to develop diagnostic and predictive tools of risk of IA.

The investigators propose to identify IA-causing variants by whole-exome sequencing in familial forms of the disease.

The investigators hypothesises that the functional analysis of the causal / susceptibility variants thus identified will provide clues to understanding the pathological mechanisms of IA formation, and the bases for developing diagnostic tools. This project aims at meeting this challenge. Based on preliminary data that already allowed to identify such a variant, and the combination of genetic and functional investigations, the specific objectives of this project are: - To identify IA-causing variants in familial forms of the disease by whole-exome sequencing; - To understand the function of these genes/ variants in the formation and rupture of IA by molecular and cellular approaches and generation of relevant animal models; - To discover potential biomarkers of risk of IA formation and/or rupture.

Being tested
Non-Interventional
Keywords
Aneurysm, Biocollection, Familial Form
Medical subject headings
Intracranial Aneurysm, Aneurysm

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Non-InterventionalGenetic

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. DNA analysis to identify new genes (and new physiological pathways) associated to the risk of intracranial aneurysm

    Measured: Until one year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Jul 2016 (estimated)
  2. Study startJan 2013
  3. Primary completionJan 2017
  4. Study completionJan 2017

Resources

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
Time perspective
Prospective
Enrolment
411 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02848495
Sponsor's protocol ID
RC12_0458
Acronym
GAÏA
Status last verified
Aug 2017
First submitted
21 Jul 2016
Last updated
11 Aug 2017
Results posted
No
Data monitoring committee
No
Individual data sharing
No

Publications

  • Canham PB, Finlay HM. Morphometry of medial gaps of human brain artery branches. Stroke. 2004 May;35(5):1153-7. doi: 10.1161/01.STR.0000124926.76836.df. Epub 2004 Mar 11.

    PubMed 15017007

  • Rhoton AL Jr. Aneurysms. Neurosurgery. 2002 Oct;51(4 Suppl):S121-58. No abstract available.

    PubMed 12234448

  • Rinkel GJ, Djibuti M, Algra A, van Gijn J. Prevalence and risk of rupture of intracranial aneurysms: a systematic review. Stroke. 1998 Jan;29(1):251-6. doi: 10.1161/01.str.29.1.251.

    PubMed 9445359

  • Vlak MH, Algra A, Brandenburg R, Rinkel GJ. Prevalence of unruptured intracranial aneurysms, with emphasis on sex, age, comorbidity, country, and time period: a systematic review and meta-analysis. Lancet Neurol. 2011 Jul;10(7):626-36. doi: 10.1016/S1474-4422(11)70109-0.

    PubMed 21641282

  • Ronkainen A, Hernesniemi J, Ryynanen M. Familial subarachnoid hemorrhage in east Finland, 1977-1990. Neurosurgery. 1993 Nov;33(5):787-96; discussion 796-97. doi: 10.1227/00006123-199311000-00001.

    PubMed 8264874

  • Haemmerli J, Morel S, Georges M, Haidar F, Chebib FT, Morita A, Nozaki K, Tominaga T, Bervitskiy AV, Rzaev J, Schaller K, Bijlenga P. Characteristics and Distribution of Intracranial Aneurysms in Patients with Autosomal Dominant Polycystic Kidney Disease Compared with the General Population: A Meta-Analysis. Kidney360. 2023 Apr 1;4(4):e466-e475. doi: 10.34067/KID.0000000000000092. Epub 2023 Feb 20.

    PubMed 36961086

  • Zuurbier CCM, Bourcier R, Constant Dit Beaufils P, Redon R, Desal H; ICAN Investigators; Bor ASE, Rinkel GJE, Greving JP, Ruigrok YM. Risk Prediction of New Intracranial Aneurysms at Follow-Up Screening in People With a Positive Family History. Stroke. 2023 Apr;54(4):1015-1020. doi: 10.1161/STROKEAHA.122.041393. Epub 2023 Feb 27.

    PubMed 36846982

  • Zuurbier CCM, Bourcier R, Constant Dit Beaufils P, Redon R, Desal H; ICAN Investigators; Bor ASE, Lindgren AE, Rinkel GJE, Greving JP, Ruigrok YM. Number of Affected Relatives, Age, Smoking, and Hypertension Prediction Score for Intracranial Aneurysms in Persons With a Family History for Subarachnoid Hemorrhage. Stroke. 2022 May;53(5):1645-1650. doi: 10.1161/STROKEAHA.121.034612. Epub 2022 Feb 11.

    PubMed 35144487

  • Bakker MK, van der Spek RAA, van Rheenen W, Morel S, Bourcier R, Hostettler IC, Alg VS, van Eijk KR, Koido M, Akiyama M, Terao C, Matsuda K, Walters RG, Lin K, Li L, Millwood IY, Chen Z, Rouleau GA, Zhou S, Rannikmae K, Sudlow CLM, Houlden H, van den Berg LH, Dina C, Naggara O, Gentric JC, Shotar E, Eugene F, Desal H, Winsvold BS, Borte S, Johnsen MB, Brumpton BM, Sandvei MS, Willer CJ, Hveem K, Zwart JA, Verschuren WMM, Friedrich CM, Hirsch S, Schilling S, Dauvillier J, Martin O; HUNT All-In Stroke; China Kadoorie Biobank Collaborative Group; BioBank Japan Project Consortium; ICAN Study Group; CADISP Group; Genetics and Observational Subarachnoid Haemorrhage (GOSH) Study investigators; International Stroke Genetics Consortium (ISGC); Jones GT, Bown MJ, Ko NU, Kim H, Coleman JRI, Breen G, Zaroff JG, Klijn CJM, Malik R, Dichgans M, Sargurupremraj M, Tatlisumak T, Amouyel P, Debette S, Rinkel GJE, Worrall BB, Pera J, Slowik A, Gaal-Paavola EI, Niemela M, Jaaskelainen JE, von Und Zu Fraunberg M, Lindgren A, Broderick JP, Werring DJ, Woo D, Redon R, Bijlenga P, Kamatani Y, Veldink JH, Ruigrok YM. Genome-wide association study of intracranial aneurysms identifies 17 risk loci and genetic overlap with clinical risk factors. Nat Genet. 2020 Dec;52(12):1303-1313. doi: 10.1038/s41588-020-00725-7. Epub 2020 Nov 16.

    PubMed 33199917

  • Bourcier R, Le Scouarnec S, Bonnaud S, Karakachoff M, Bourcereau E, Heurtebise-Chretien S, Menguy C, Dina C, Simonet F, Moles A, Lenoble C, Lindenbaum P, Chatel S, Isidor B, Genin E, Deleuze JF, Schott JJ, Le Marec H; ICAN Study Group; Loirand G, Desal H, Redon R. Rare Coding Variants in ANGPTL6 Are Associated with Familial Forms of Intracranial Aneurysm. Am J Hum Genet. 2018 Jan 4;102(1):133-141. doi: 10.1016/j.ajhg.2017.12.006.

    PubMed 29304371

Questions about this trial

What is this clinical trial studying?

An observational study of Intracranial Aneurysm, run by Nantes University Hospital at 8 sites in France.

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 7 inclusion and 15 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 11 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in France. 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?

DNA analysis to identify new genes (and new physiological pathways) associated to the risk of intracranial aneurysm (time frame: Until one year). 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 NCT02848495, which also lists 10 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 11 Aug 2017.

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