Clinical trial NCT03493035: Risk Factors of Middle Cerebral Artery Aneurysm.
Official title: A Case-control Study of Independent Predictors of Middle Cerebral Artery Aneurysm.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Middle Cerebral Artery Aneurysm
Keywords: Middle Cerebral Artery
Cerebral Aneurysm
Transcranial Color-Coded Sonography
Three-Dimensional Computed Tomography Angiography
Lead sponsor: Medical University of Silesia
Sponsor class: OTHER
First posted: 2018-04-10
Enrollment: 190
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study will include patients (further referred to as cases) with unruptured MCA aneurysm diagnosed on three-dimensional computed tomography angiography (3D CTA).

The controls will be patients with no evidence of intracranial pathologies on 3D CTA, referred to establish the etiology of minor symptoms, such as headache or vertigo.

Brief summary: According to the current view, cerebral aneurysms are acquired degenerative lesions resulting from hemodynamic stress. This single-center case-control study will be carried out at the Department of Neurosurgery, Regional Hospital in Sosnowiec, Medical University of Silesia in Katowice, Poland between June 2015 and June 2017. The aim of the study is to determine morphometric and hemodynamic parameters of aneurysmal and non-aneurysmal middle cerebral artery (MCA) bifurcations and to analyze their relationship with aneurysm formation. A minimum of 75 cases and 75 age- and sex-matched controls will be required for the study. Characteristics of the MCA bifurcations will be determined with computed tomography angiography (CTA) and transcranial color-coded sonography (TCCS). The following variables will be evaluated as potential risk factors for MCA aneurysm formation: radii and cross-sectional area of the main MCA trunk and its branches, tortuosity of MCA trunk, asymmetry ratio, area ratio, the angle between the post-bifurcation branches, the angles between the MCA trunk and the larger and smaller branch, volume flow rate, mean flow velocity and pulsatility index of the MCA. All morphometric and hemodynamic parameters will be assessed as potential risk factors for MCA aneurysm formation.

Detailed description: Current evidence suggests that a principal factor involved in formation, enlargement and rupture of cerebral aneurysms are hemodynamic forces acting at arterial bifurcation. The objective of this case-control study is to determine morphometric and hemodynamic parameters of aneurysmal and non-aneurysmal MCA bifurcations and to analyze their relationship with aneurysm formation. This single-center case-control study will be carried out at the Department of Neurosurgery, Regional Hospital in Sosnowiec, Medical University of Silesia in Katowice, Poland between June 2015 and June 2017. The study will include patients (cases) with unruptured MCA aneurysm diagnosed on three-dimensional computed tomography angiography (3D CTA). The controls will be patients with no evidence of intracranial pathologies on 3D CTA, referred to establish the etiology of minor symptoms, such as headache or vertigo. A minimum of 75 cases and 75 age- and sex-matched controls will be required for the study.

CTA scans data in DICOM format will be transferred to Mimics Innovation Suite (MIS) platform (Materialise, Leuven, Belgium). Image segmentation and creation of three-dimensional (3D) models will be carried out with Mimics v.17.0 MIS software (Materialise, Leuven, Belgium). The segmentation process will include main trunks of the MCA and the post-bifurcation branches. Trifurcations of the main MCA trunk will be excluded from the morphometric analysis. MCA bifurcations from the aneurysm patients will be divided into two groups: the An group with aneurysmal MCA bifurcations and the non-An group with contralateral non-aneurysmal MCA bifurcations. Also, MCA bifurcations from the controls will be divided into two groups: R-MCA group with bifurcations of the right MCA and the L-MCA group with bifurcations of the left MCA. Morphometric analysis will include the following parameters: radii and cross-sectional area of the main MCA trunk and its branches (for the larger and smaller branch, respectively), tortuosity of MCA trunk, asymmetry ratio, area ratio, the angle between the post-bifurcation branches, the angles between the MCA trunk and the larger and smaller branch. All TCCS examinations will be performed using a Vivid 3 Pro (GE Healthcare, Chicago, Illinois, USA) equipped with a multi-frequency transcranial probe (1.5-3.6 MHz). Angle-corrected mean blood flow velocity, peak systolic velocity and end-diastolic velocity will be measured for both MCAs. Pulsatility index and volume flow rate in each vessel will be calculated as well. The protocol of the study was approved by the Institutional Review Board, and written informed consent will be sought from all the study participants. All morphometric and hemodynamic parameters will be assessed as potential risk factors for MCA aneurysm formation.

Eligibility criteria: Definition and recruitment of cases The study will include patients (further referred to as cases) with unruptured MCA aneurysm diagnosed on three-dimensional computed tomography angiography (3D CTA).

Case inclusion criteria

* all patients with unruptured MCA aged between 18-75 years Case exclusion criteria
* refusal to participate in the study
* inability to give informed consent
* presence of multiple cerebral aneurysms
* presence of pathologies, other than MCA aneurysm, in the central nervous system that could have a potential effect on cerebral blood flow (e.g. ischemic stroke, intracerebral or subarachnoid hemorrhage)
* severe systemic disorders (e.g. neoplastic disease)
* severe heart failure or multi-organ failure
* hemodynamically significant internal carotid artery stenosis
* pregnancy
* family history of cerebral aneurysms.

Definition and recruitment of controls The controls will be patients with no evidence of intracranial pathologies on 3D CTA, referred to establish the etiology of minor symptoms, such as headache or vertigo.

Inclusion criteria for the controls

* all patients aged between 18-75 years with no evidence of intracranial pathologies on 3D CTA Exclusion criteria for the controls
* refusal to participate in the study
* inability to give informed consent
* presence of pathologies in the central nervous system that could have a potential effect on cerebral blood flow (e.g. ischemic stroke, intracerebral or subarachnoid hemorrhage)
* severe systemic disorders (e.g. neoplastic disease)
* severe heart failure or multi-organ failure
* hemodynamically significant internal carotid artery stenosis
* pregnancy
* family history of cerebral aneurysms.

Primary outcomes:
measure: Computed tomography angiography (CTA) analysis of the cross-sectional area of the MCA bifurcations.
timeFrame: from 16 June 2015 to 15 June 2017
measure: Computed tomography angiography (CTA) analysis of the best fit diameter of the MCA bifurcations.
timeFrame: from 16 June 2015 to 15 June 2017
measure: Computed tomography angiography (CTA) analysis of the angles between the MCA bifurcations components.
timeFrame: from 16 June 2015 to 15 June 2017
measure: Pulsatility Index (PI) as calculated from transcranial color-coded sonography (TCCS) blood flow velocities (cm/s)
timeFrame: from 16 June 2015 to 15 June 2017
measure: Volume Flow Rate (VFR) as calculated from transcranial color-coded sonography (TCCS) blood flow velocities (cm/s)
timeFrame: from 16 June 2015 to 15 June 2017
Secondary outcomes:
Other outcomes:
Locations:
city: Sosnowiec
country: Poland
facility: Wojciech Kaspera
state: Smorzykk@gmail.com
Study officials:
affiliation: Medical University of Silesia
name: Wojciech Kaspera, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Sasaki T, Kakizawa Y, Yoshino M, Fujii Y, Yoroi I, Ichikawa Y, Horiuchi T, Hongo K. Numerical Analysis of Bifurcation Angles and Branch Patterns in Intracranial Aneurysm Formation. Neurosurgery. 2019 Jul 1;85(1):E31-E39. doi: 10.1093/neuros/nyy387.