ECAA Brain MRI: Seeking the Link Between Extracranial Carotid Artery Aneurysms and Small Vessel Disease

Seeking the Link Between Extracranial Carotid Artery Aneurysms and Small Vessel Disease

In order to understand which ECAA patients benefit from medical therapy, more should be known about the possible outcomes of this rare disease. Small vessel disease seen on brain MRI's could be a good marker to assess possible silent cerebrovascular disease caused by ECAA's, suggesting underlying generalized vascular disease. With this knowledge, medical therapy for ECAA patients can be optimized and individualized to treat possible generalized vascular disease, aiding physicians in choosing a treatment strategy.

Study Overview

• Status: Recruiting
• Conditions: Extracranial Carotid Artery Aneurysm
• Intervention / Treatment: Diagnostic test: MRI

Detailed Description

The ECAA brain MRI study is a monocenter longitudinal observational cohort study, initiated by the Department of Vascular Surgery at the University Medical Center Utrecht (UMCU), The Nederlands. The study aims to recruit 50 participants with an extracranial carotid artery aneurysm (ECAA) who are currently receiving conservative treatment. Patients will undergo MRI at baseline and after 2 years of follow-up. The expected duration of the study is approximately 3 years. The study will be conducted according to the principles of the Declaration of Helsinki (64th WMA General Assembly, Fortaleza, Brazil, October 2013). The medical ethics committee of the UMCU has approved the study. To be eligible to be included in the ECAA brain MRI, patients must be enrolled in the Carotid Aneurysm Registry (CAR, NCT02229370)

• Study Type: Observational
• Enrollment (Anticipated): 50

Contacts and Locations

Study Locations

• Netherlands
  • Zuid Holland
    • Utrecht, Zuid Holland, Netherlands
      • Recruiting
      • UMCU
      • Contact: Gert Jan de Borst; Phone Number: +31-88-7556965; Email: g.j.deBorst-2@umcutrecht.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The study population comprises patients with extracranial carotid artery aneurysm (ECAA) from the Netherlands, aged 18 years or older, of any gender, race, and medical history except for those with neurovascular diseases such as Parkinson's disease and multiple sclerosis.

Description

Inclusion Criteria:

• Patient older than 18 years registered in the CAR treated with conservative therapy
• Willingness and ability to participate in all scheduled procedures outlined in the protocol
• Understanding of the Dutch language
• Patient is able and willing to give informed consent.

Exclusion Criteria:

• Inclusion criteria are not met
• Subjects registered in the CAR that have undergone surgical or endovascular treatment of the ECAA
• Contradictions for MRI, such as 1) metallic objects in or around the body (e.g. cardiac implantable electronic device such as pacemakers and implantable cardioverter defibrillators (ICD); 2) claustrophobia, 3) pregnancy.
• Other major neurological or psychiatric conditions affecting the brain and interfering with the study design (e.g. multiple sclerosis, epilepsy, Parkinson's disease, vascular dementia)
• Unable to read or write the patient information letter and broad consent file
• Patients who have a life expectancy of less than two years due to a pre-existing condition e.g. cancer

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
ECAA patient; ECAA patient recieving conservative treatment	Diagnostic test: MRI; Patients will be asked for two additional control visits in the hospital. Overview of measurements: Included subject will visit the UMCU at two occasions. The first MRI scan will be the baseline MRI, and the second MRI will take place after 2 years of follow-up. Additional follow-up data will be collected through medical records reporting on regular follow-up.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Small vessel disease in ECAA patients	To assess the presence of ipsilateral small vessel disease (i.e. WMHs, lacunes, microbleeds, perivascular spaces, and recent small subcortical infarcts) based on 3 tesla (3T) brain MRI in patients with ECAA	2023-2025

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Small vessel disease in ECAA patients in time	To investigate the progression of small vessel disease over time. Title: Progression of small vessel disease in ECAA patients over time Description: This study aims to investigate the progression of small vessel disease in ECAA patients over a two-year period, as measured by white matter hyperintensity (WMH) volume in ml on MRI scans at baseline and two-year follow-up, as well as the presence of lacunar infarcts on MRI scans. Unit of measure: WMH volume in ml Measurement tool: MRI scans Other small vessel disease: Presence of lacunar infarcts, perisvascular spacesm, lacunes, microbleeds on MRI scans, counted manually	24months
Small vessel disease uni/bilateral	Outcome Measure Title: Unilateral vs. Bilateral Small Vessel Disease in ECAA Patients Description: This outcome measure will assess whether small vessel disease in ECAA patients occurs unilaterally or bilaterally. White matter hyperintensities will be measured by calculating the volume of white matter hyperintensities (WMH) in milliliters (ml) on MRI scans. Unilateral small vessel disease will be defined as WMH volume greater on the same side as the ECAA, while bilateral small vessel disease will be defined as WMH volume roughly equal on both sides. Other small vessel disease will be scored as a number (as a number of lacunair infarcts) and comapered uni- an bilaterally to the affected carotid side.	24months
Silent brain lesions	To investigate the presence and localisation of silent brain lesions in ECAA patients	24months
Aneurysm morphology.	To assess the association between aneurysm characteristics and small vessel disease burden.Outcome Measure Title: Correlation Between Aneurysm Characteristics and Small Vessel Disease Burden Unit of Measure: Correlation Coefficient (r) Measurement Tool: Statistical Analysis Description: The correlation between aneurysm characteristics (such as size, location, and shape) and small vessel disease burden (such as white matter hyperintensities and lacunar infarcts) will be assessed using a correlation analysis. The correlation coefficient (r) will be calculated to determine the strength and direction of the relationship between the two variables.	24months
Flow in ECAA	To investigate the pulsatility in the in the carotid artery based on 3T MRI imaging. Outcome Measure Title: Pulsatility Index (PI) in the Carotid Artery Measured by 3T MRI Imaging Unit of Measure: Pulsatility Index (%) Measurement Tool: 3T MRI Imaging Description: The pulsatility index (PI) will be calculated by measuring the peak systolic velocity and end-diastolic velocity of blood flow in the carotid artery using 3T MRI imaging. The PI will be calculated using the following formula: PI = (peak systolic velocity - end-diastolic velocity) / mean velocity.	24months
Flow in ECAA	To investigate the distensibility in the in the carotid artery based on 3T MRI. Outcome Measure Title: Carotid Artery Distensibility Measured by 3T MRI Imaging Unit of Measure: Distensibility (mmHg^-1 x 10^-3) Measurement Tool: 3T MRI Imaging Description: The distensibility of the carotid artery will be measured using 3T MRI imaging by acquiring cine images of the carotid artery during the cardiac cycle. The distensibility will be calculated using the following formula: distensibility = [(A_max - A_min) / A_min] / [Pulse pressure], where A_max and A_min are the maximum and minimum areas of the carotid artery lumen during the cardiac cycle, respectively, and Pulse pressure is the difference between systolic and diastolic blood pressures.	24months

Collaborators and Investigators

• Sponsor: UMC Utrecht

Publications and helpful links

General Publications

• Wardlaw JM, Smith EE, Biessels GJ, Cordonnier C, Fazekas F, Frayne R, Lindley RI, O'Brien JT, Barkhof F, Benavente OR, Black SE, Brayne C, Breteler M, Chabriat H, Decarli C, de Leeuw FE, Doubal F, Duering M, Fox NC, Greenberg S, Hachinski V, Kilimann I, Mok V, Oostenbrugge Rv, Pantoni L, Speck O, Stephan BC, Teipel S, Viswanathan A, Werring D, Chen C, Smith C, van Buchem M, Norrving B, Gorelick PB, Dichgans M; STandards for ReportIng Vascular changes on nEuroimaging (STRIVE v1). Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration. Lancet Neurol. 2013 Aug;12(8):822-38. doi: 10.1016/S1474-4422(13)70124-8.
• Welleweerd JC, den Ruijter HM, Nelissen BG, Bots ML, Kappelle LJ, Rinkel GJ, Moll FL, de Borst GJ. Management of extracranial carotid artery aneurysm. Eur J Vasc Endovasc Surg. 2015 Aug;50(2):141-7. doi: 10.1016/j.ejvs.2015.05.002. Epub 2015 Jun 24.
• van Laarhoven CJHCM, Rots ML, Pourier VEC, Jorritsma NKN, Leiner T, Hendrikse J, Vergouwen MDI, de Borst GJ. Gadolinium Enhancement of the Aneurysm Wall in Extracranial Carotid Artery Aneurysms. AJNR Am J Neuroradiol. 2020 Mar;41(3):501-507. doi: 10.3174/ajnr.A6442. Epub 2020 Feb 27.
• Ghaznawi R, Geerlings MI, Jaarsma-Coes M, Hendrikse J, de Bresser J; UCC-Smart Study Group. Association of White Matter Hyperintensity Markers on MRI and Long-term Risk of Mortality and Ischemic Stroke: The SMART-MR Study. Neurology. 2021 Apr 27;96(17):e2172-e2183. doi: 10.1212/WNL.0000000000011827. Epub 2021 Mar 16.

Study record dates

Study Major Dates

• Study Start (Actual): March 30, 2023
• Primary Completion (Anticipated): April 1, 2025
• Study Completion (Anticipated): April 1, 2025

Study Registration Dates

• First Submitted: March 30, 2023
• First Submitted That Met QC Criteria: April 12, 2023
• First Posted (Actual): April 25, 2023

Study Record Updates

• Last Update Posted (Actual): April 25, 2023
• Last Update Submitted That Met QC Criteria: April 12, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Aneurysm
• Other Study ID Numbers: 22-781

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No