99m Tc-ANNexin-V-128 Scintigraphy for the Identification of Complicated Carotid Atherosclerotic Plaques

NCT ID: NCT03630835

Last Updated: 2021-10-20

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2/PHASE3
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-09-30
• Study Completion Date: 2020-04-30

Brief Summary

The aim of this trial will be to test and validate the value of scintigraphy with injection of 99mTc-Annexin-V-128 for the detection of complicated carotid plaques

Detailed Description

Introduction Stroke represents the third cause of death, the first cause of handicap and the second cause of dementia in Europe. Carotid atherosclerotic plaques are the cause of ischemic stroke in about 15 to 20 % of the patients. In presence of carotid stenosis > 50 %, the risk of ischemic stroke is estimated at about 10% per year when the patient has presented symptoms of cerebral ischemia but only at 2% per year in asymptomatic patients. Clinical benefits of surgical carotid endarterectomy have been demonstrated in symptomatic patients with high degree of carotid stenosis, but remain debatable in asymptomatic patients and should be balanced with the risks associated with the revascularization procedure. There is an urgent need to develop imaging tools that improve the identification of patients at highest risk of developing an ischemic stroke Cellular apoptosis is a key feature of ruptured plaques. Apoptotic macrophages release large amounts of tissue factor within the plaque thereby fostering thrombus formation when plaques rupture. Annexin-V is a 36-kDa protein that binds with high affinity and high specificity to phosphatidylserine (PS) head groups expressed on the cell surface at early stages of the apoptotic process. In addition, activated platelets express large amounts of PS at their surface. In a proof-of-concept study, 99mTc-Annexin-V uptake was detected by scintigraphy in carotid atherosclerotic plaques of 4 patients who presented an acute ischemic stroke and was associated with the presence of apoptotic cells on corresponding carotid plaques obtained after carotid endarterectomy procedure.

Design : Monocentric interventional non comparative study Investigational medicinal product(s): 99mTc-Annexin-V-128 Statistical procedure : Statistical analysis will be performed at the end of the study after blinded review and data freezing.

99mTc-Annexin-V-128 uptake will be analyzed as a binary variable considering the presence or absence of detection and as a quantitative variable for the intensity of signal.

Conditions

Carotid Atherosclerosis; Atherosclerotic Plaque

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: SCREENING
• Blinding Strategy: NONE

Study Groups

99mTc-Annexin-V-128 uptake on scintigraphy

Group Type: EXPERIMENTAL

99mTc-Annexin-V-128 uptake on scintigraphy

Intervention Type: OTHER

An intravenous catheter will be placed in the forearm and a dose of 370 Mega-Becquerels of 99mTc-Annexin-V-128 (1-2 ml) over 10 seconds will be injected through the catheter. The patient will wait for 90 minutes in semi-supine position for the clearance of the radiotracer from blood. At 90 minutes p.i., the patient will be placed in a supine position on the bed of a SPECT-CT gamma-camera. A SPECT acquisition including the heart and the brain will be performed over 20 minutes. At the end of the SPECT acquisition, the bed will move to the CT of the imaging system. A CT angiography will be acquired during the intravenous injection of 30-40 ml of iodinated CT contrast agent from the heart to the brain to localize the signal on the SPECT images. The iodinated contrast agent that is currently available at Bichat Hospital for CTA is Iomeron 400 provided by Bracco Imaging.

The total duration of the imaging study will be 2 hours.

Interventions

99mTc-Annexin-V-128 uptake on scintigraphy

An intravenous catheter will be placed in the forearm and a dose of 370 Mega-Becquerels of 99mTc-Annexin-V-128 (1-2 ml) over 10 seconds will be injected through the catheter. The patient will wait for 90 minutes in semi-supine position for the clearance of the radiotracer from blood. At 90 minutes p.i., the patient will be placed in a supine position on the bed of a SPECT-CT gamma-camera. A SPECT acquisition including the heart and the brain will be performed over 20 minutes. At the end of the SPECT acquisition, the bed will move to the CT of the imaging system. A CT angiography will be acquired during the intravenous injection of 30-40 ml of iodinated CT contrast agent from the heart to the brain to localize the signal on the SPECT images. The iodinated contrast agent that is currently available at Bichat Hospital for CTA is Iomeron 400 provided by Bracco Imaging.

The total duration of the imaging study will be 2 hours.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• 18 years ≤ Age ≤ 90 years
• Patients with clinical indications to carotid endarterectomy
• Signed the consent form.
• Affiliation of a social security regime

Exclusion Criteria

• Non-menopausal women
• Chronic kidney disease (eGFR < 45 ml/min/1.73 m2)
• Waldenstrom disease
• Multiple myeloma
• Previous severe adverse reaction to iodinated contrast agent
• Impossibility to stay immobile and maintain the supine position during 20 minutes.
• Altered consciousness or inability to understand the consent form.
• Urinary incontinence without implantation of urinary catheter (risk of urinary contamination).
• Non-atherosclerotic carotid stenosis (history of cervical radiation).
• Patient deprived of liberty or under legal protection measure

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Pierre AMARENCO, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Assistance Publique - Hôpitaux de Paris

Other Identifiers

2017-002952-99

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

P170602

Identifier Type: -

Identifier Source: org_study_id