Carotid Atherosclerosis : Innovative Imaging Biomarkers. Study Case-control (ACABII)

Cerebrovascular accident (CVA) constitutes a major health public problem. This represents the second cardiovascular death cause. CVA is ischemic in 80% of cases. Atheroma of large arteries, mainly carotid, is involved in about 20% of cases.

After several high grade studies (NASCET, ECST, ACAS, ACST), carotid surgery is based on stenosis calculation by Doppler ultrasound, CT angiography, MRI angiography or arteriography.

The composition of the plaque, showing its vulnerability, is associated with embolic risk and stroke. The therapeutic strategy based only on the narrowing of the arterial lumen is not satisfactory enough to prevent the occurrence of a transient ischemic attack (TIA) or an ipsilateral stroke due to carotid stenosis. Thus, new techniques emerge, to evaluate in vivo the inflammation of the plaque, its embolic consequences or the mechanical stress it undergoes. These techniques are: High Resolution MRI (HR MRI), evaluation of the Gray Scale Median (GSM) level, study of the plaque vascularization with Contrast Enhanced ultrasound (CEUS), High Intensity Transient Signals (HITS) by transcranial Doppler, micro RNA profile (mi RNA). These different modalities must be combined in order to increase the efficiency.

Based on these encouraging results, the investigator aim at evaluating the ability of different methods or their combination to predict the occurrence of ischemic stroke or TIA due to emboli from a carotid atherosclerotic plaque. Before considering a cohort study, he investigator want to evaluate the performance of each of these new methods in the characterization of carotid plaque instability. Performance evaluation will allow us to choose secondarily the most relevant association.

The investigator propose, as a first step, to make a case-control study with these methods, the cases are patients who had an ischemic stroke (authenticated by both the clinical exam and brain MRI) on the same side as the carotid stenosis and the controls are patients with carotid stenosis but without ischemic stroke. This study is a cross-sectional study because it simultaneously measures the occurrence of the event (ischemic stroke) and the characteristics of the atheromatous plaque.

Over a 2 year period, 45 symptomatic patients and 105 asymptomatic patients will be included with a carotid stenosis with at least a 50% caliber constriction according to NASCET criteria. (North American Symptomatic Carotid Endarterectomy Trial).

Study Overview

• Status: Recruiting
• Conditions: Carotid Stenosis
• Intervention / Treatment: Device: HITS quantification, Ultrasound examinations, High Resolution MRI

• Study Type: Interventional
• Enrollment (Anticipated): 77
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Philippe DOUEK, MD; Phone Number: +33 (0)472357233; Email: philippe.douek@chu-lyon.fr
• Study Contact Backup: Name: Adeline MANSUY, CRA; Phone Number: +33 (0)4 72 11 5225; Email: adeline.mansuy@chu-lyon.fr

Study Locations

• France
  • Bron, France, 69500
    • Recruiting
    • Hospices Civils de Lyon - Service de radiologie
    • Contact: Philippe DOUEK, MD; Phone Number: +33 0472357233; Email: philippe.douek@chu-lyon.fr
    • Contact: Adeline MANSUY; Phone Number: +33 4 72 11 52 25; Email: adeline.mansuy@chu-lyon.fr
    • Principal Investigator: Stéphane Luong, MD
    • Sub-Investigator: Laura MECHTOUFF, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Carotid stenosis ≥ 50% NASCET
• Case: ipsilateral carotid stenosis stroke, certified by MRI or CT in the preceding month, with no others causes of stroke
• Control: no clinical sign or MRI hint for a recent stroke
• Signed informed consent form
• Patient affiliated to a social security system or equivalent

Exclusion Criteria:

• Modified Rankin scale > 3
• Homolateral stroke or TIA > 1 month
• Medical history of homolateral carotid surgery, cervical radiation, carotid occlusive, homolateral intracranial stenosis, risk of developing arterial thromboembolic events
• Renal failure (creatinine clearance < 50 ml/min)
• Contraindication to ultrasound (sonovue)
• Contraindication to MRI and its contrast media (Gadolinium)
• Inability to sign informed consent
• Inability to undergo any of the technics (claustrophobia…)
• Serious co-morbid disease, dementia
• Neurological disease with no carotid disease
• Risk of pregnancy or pregnancy or breastfeeding
• Adult under reinforced guardianship or legal guardian
• Patient not understanding French

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: symptomatic and asymptomatic patients

Device: HITS quantification, Ultrasound examinations, High Resolution MRI; Simultaneously measure the occurrence of the event (ischemic stroke) and the characteristics of the atheromatous plaque Description of different modalities: HITS quantification Ultrasound examinations: Ulceration >2 mm; Plaque thickness; GSM: computer analysis after normalization of most informative longitudinal view (image with maximum plaque area) using Photoshop; CEUS: plaque vascularization detection after bolus injection of SONOVUE on a video recording from the injection of the contrast (Vuebox - Bracco imaging) High Resolution MRI: Stenosis severity, intraplaque hemorrhage, large lipid-rich necrotic core, ulceration or cap rupture and Brain MRI will be evaluated; Quantification of shear stresses (Pa) on the surface of the plaque mi-RNA identification and quantification

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of HITS per hour in doppler ultrasonography		Day 1
Ulceration > 2 mm presence in doppler ultrasonography		Day 1
GSM (Gray Scale Median) quantification in doppler ultrasonography		Day 1
CEUS (Contrast Enhanced UltraSound )	signal intensity amplification quantification and Ulceration > 2 mm	Day 1
hemorrhage intra-plaque présence in HR MRI		Day 1
large lipid-rich necrotic core présence in HR MRI		Day 1
ulceration or cap rupture présence in HR MRI		Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
hemorrhage intra-plaque	Compare the results of each modality for pathological analysis of the surgical equipment.	Day 1
large lipid-rich necrotic core	Compare the results of each modality for pathological analysis of the surgical equipment.	Day 1
ulceration or cap rupture	Compare the results of each modality for pathological analysis of the surgical equipment.	Day 1
shear stresses (Pa) on the surface of the plaque	Quantification of the shear stresses (Pa) on the surface of the plaque with an analysis of hemodynamic environment using fluid dynamics mathematical models based on data collected by MRI.	Day 1
mi-RNA identification	Identification of circulating mi-RNA specific to unstable atherosclerotic plaque by RT-PCR and comparison between case and control	Day 1

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon
• Collaborators: Fondation de France; Bracco Imaging S.p.A.

Study record dates

Study Major Dates

• Study Start (Actual): January 12, 2017
• Primary Completion (Anticipated): February 12, 2024
• Study Completion (Anticipated): February 12, 2024

Study Registration Dates

• First Submitted: April 11, 2016
• First Submitted That Met QC Criteria: April 19, 2016
• First Posted (Estimate): April 22, 2016

Study Record Updates

• Last Update Posted (Actual): April 28, 2023
• Last Update Submitted That Met QC Criteria: April 27, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: CEUS; mi-RNA; unstable/stable atherosclerotic plaque; HITS; GSM; HR MRI
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Arterial Occlusive Diseases; Carotid Artery Diseases; Carotid Stenosis
• Other Study ID Numbers: 69HCL15_0458

Plan for Individual participant data (IPD)

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