Plaque and Brain Inflammation in Symptomatic Carotid Stenosis: Role of the Ficolin-2 (STATEMENT)

Carotid artery stenosis is observed in about 3% of ≥ 60 years subjects and accounts for around 10-20% of all ischemic strokes. Beyond the degree of stenosis, plaque composition affects the risk of ischemic stroke. Identification of patients with vulnerable plaques at higher risk of stroke who might benefit from carotid revascularization is crucial.

A growing body of evidence suggests that the lectin pathway of the complement system, and especially the ficolin-2, is involved in atherosclerosis. It has been hypothesized that circulating levels of ficolin-2 increase during chronic inflammatory conditions (i.e. growing atherosclerotic plaque) whereas they fall during sub-acute or acute inflammatory conditions (i.e. plaque rupture and acute ischemic stroke) because of consumption (binding to targets). Therefore, ficolin-2 has been proposed as a biomarker informing on the specific state of the plaque. However, in acute ischemic stroke due to carotid stenosis, both plaque rupture and stroke injury contribute to lectin pathway activation, thus affecting circulating levels of ficolin-2. Until now, the relative contribution of plaque and brain inflammation on circulating levels of ficolin-2 has not been documented.

In the present study the investigators aim to assess the association between circulating levels of ficolin-2 and carotid and brain inflammation on [18F]DPA-714 positron emission tomography (PET)/MRI in patients with transient ischemic attack or acute ischemic stroke due to carotid stenosis. For that purpose, the investigators intend to include 30 patients with transient ischemic attack or acute ischemic stroke due to ≥ 50%. carotid stenosis. Each patient will have a measure of plasmatic level of ficolin-2 as well a [18F]DPA-714 PET/MRI to quantify the fixation of the radiotracer on carotid and brain.

Study Overview

• Status: Recruiting
• Conditions: CAROTID STENOSIS
• Intervention / Treatment: Drug: [18F]DPA-714 PET/MRI

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Laura MECHTOUFF; Phone Number: +33 4.27.85.67.47; Email: laura.mechtouff@chu-lyon.fr
• Study Contact Backup: Name: Naoual EL JONHY; Phone Number: +33 4.72.35.69.12; Email: naoual.el-jonhy@chu-lyon.fr

Study Locations

• France
  • Bron, France, 69500
    • Recruiting
    • Service de Neurologie vasculaire / CarMeN U1060 INSERM Hôpital Neurologique Pierre Wertheimer - GHE
    • Contact: Laura MECHTOUFF, MD; Phone Number: +33 04.27.85.67.47; Email: laura.mechtouff@chu-lyon.fr

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patients 18 years or over,
• Signed written informed consent before any study specific intervention,
• Probable ipsilateral transient ischemic attack (TIA - which involve a focal speech/language, motor or visual deficit referable to the distribution of a carotid artery and lasting less than 48 hours from the onset) OR retinal artery occlusion ≤ 48h OR ischemic stroke ≤ 48h from the onset,
• Atherosclerotic carotid stenosis between 50% and 99% (NASCET method), as confirmed by one of the imaging examinations (among: Doppler ultrasound, MR angiography, CT angiography, catheter angiography) performed after index TIA or ischemic stroke
• No other identified cause of TIA, ischemic stroke or retinal artery occlusion,

Exclusion Criteria:

• Patients with inflammatory or autoimmune disease, hepatocellular insufficiency, acute or chronic infection, active malignancy, myocardial infarction or major surgery within the previous 30 days of index hospitalization according to the investigator,
• Patients with severe renal insufficiency (estimated GFR < 30 ml/min at inclusion or known dialysis),
• Patients with contraindication to MRI (agitation, claustrophobia, pacemaker, metallic (ferromagnetic) body, a known allergy to gadolinium) according to the investigator's judgment,
• Patients with modified Rankin score greater than 3,
• Patients currently enrolled in another clinical trial including investigational medicinal products,
• Female patient who is pregnant or lactating, or is of child-bearing and who did not agree to use highly effective methods of birth control throughout the study,
• Patient without health coverage,
• Patient under legal protection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• 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: [18F]DPA-714 PET/MRI	Drug: [18F]DPA-714 PET/MRI; To assess the association between plasma ficolin-2 levels and plaque and brain inflammation assessed by [18F]DPA-714 PET/MRI in patients managed for transient ischaemic attack or ischaemic stroke related to carotid stenosis. PET/MRI of the brain and carotid plaque with [18F]DPA-714 and gadolinium infusion will be performed at day 5.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation between: - Plasma levels of ficolin-2 at day 5 in ng/ml, - Metabolic data on [18F]DPA-714 PET/MRI	To assess the association between circulating levels of ficolin-2 and carotid and brain inflammation on [18F]DPA-714 PET/MRI in patients with transient ischemic attack or acute ischemic stroke due to carotid stenosis	day 5

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation between plasma levels of ficolin-2 at day 5 in ng/mL with morphological data of the brain and carotid plaque assessed by MRI	To assess if plasma levels of ficolin-2 in patients with TIA or acute ischemic stroke due to carotid stenosis correlate with: 1. morphological data: of the plaque: presence of intraplaque hemorrhage, lipid-rich necrotic core, thinning/rupture of the fibrous cap on carotid plaque MRI; of the brain: infarct size, presence of hemorrhagic transformation, blood-brain barrier leakage	day 5
Correlation between plasma levels of ficolin-2 at day 5 in ng/mL with morphological data of the brain and carotid plaque assessed by MRI	To assess if plasma levels of ficolin-2 in patients with TIA or acute ischemic stroke due to carotid stenosis correlate with: - histological data of the retrieved plaque: hemorrhagic content, lipid core, cholesterol cleft areas, ratio between thickness of tunica media and total thickness of tunica, rupture, intraplaque deposition of ficolin-2, macrophages and neutrophils infiltration	day 15

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon
• Investigators: Principal Investigator: Laura MECHTOUFF, Service de Neurologie vasculaire / CarMeN U1060 INSERM

Study record dates

Study Major Dates

• Study Start (Actual): February 13, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: April 28, 2023
• First Submitted That Met QC Criteria: April 28, 2023
• First Posted (Actual): May 9, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 3, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neuroinflammatory Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Anatomical; Infections; Arterial Occlusive Diseases; Central Nervous System Infections; Carotid Artery Diseases; Infectious Encephalitis; Inflammation; Constriction, Pathologic; Encephalitis; Carotid Stenosis
• Other Study ID Numbers: 69HCL20_0403; 2023-504573-20 (EudraCT Number)

Drug and device information, study documents

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