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

Phase 2

Recruiting

• Conditions: CAROTID STENOSIS
• Interventions: Drug: [18F]DPA-714 PET/MRI

• Registration Number: NCT05850247
• Lead Sponsor: Hospices Civils de Lyon

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-04-28
• Study First Submitted QC: 2023-04-28
• Study First Posted: 2023-05-09
• Study Start: 2024-02-13
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-03
• Last Update Posted: 2025-02-06
• Primary Completion: 2026-12-31
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 20

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
[18F]DPA-714 PET/MRI	[18F]DPA-714 PET/MRI	-

Primary Outcome Measures

Name	Time	Method
Correlation between: - Plasma levels of ficolin-2 at day 5 in ng/ml, - Metabolic data on [18F]DPA-714 PET/MRI	day 5	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

Secondary Outcome Measures

Name	Time	Method
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	day 15	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

Trial Locations

Locations (1)

Service de Neurologie vasculaire / CarMeN U1060 INSERM Hôpital Neurologique Pierre Wertheimer - GHE; 🇫🇷 Bron, France