IMaging Della PLAcca Carotidea

NCT03333330 | Completed Phase 3 DMC

• 1 other identifier: GR-2009-1608780
• Study Type: interventional
• Target: 75
• Locations: 0 countries
• Sites: N/A

Brief Summary

Background-White matter hyperintensities (WMH), patchy areas of hyperintense signal on T2-weighted or Fluid Attenuated Inversion Recovery sequences on brain magnetic resonance imaging (MRI), are believed to reflect cerebral burden of ischemic damage and are associated to incident stroke, dementia and eventually mortality in otherwise healthy subjects. Also brain atrophy has been related with presence of carotid atherosclerosis and vascular cognitive impairment. Carotid atherosclerosis may contribute to the genesis of WMH. A recent meta-analysis by our group comprising 5306 subjects was able to demonstrate an association between the presence of carotid atherosclerosis and WMH (odds ratio, OR, 1.42, 95% confidence interval \[CI\] 1.22-1.66). Objective-To evaluate the relation between carotid artery plaque characteristics, cardiovascular risk factors and brain atrophy/WMH burden analyzed quantitatively as number and volume of lesions and as brain volumes, and progression over 18 months of follow up in subjects asymptomatic for cerebrovascular disease with a carotid artery stenosis \<70%.

Conditions

Carotid Artery Plaque; Atherosclerosis; Ischemic Stroke

Keywords

Carotid atherosclerosis; Carotid plaque; Brain magnetic resonance imaging; Contrast enhanced ultrasound; Carotid CT angiography; Silent brain ischemia; Vascular cognitive impairment

Outcome Measures

Primary Outcomes (1)

• Changes of total cerebral white matter lesions from baseline (T2-weight lesions, in terms of number and total volumes indexed to the total brain volume)

  We expect that asymptomatic patients with carotid atherosclerosis with characteristics of vulnerability of the plaque can develop a larger burden of silent cerebral ischemic lesions along the timeframe of the study. We are going to compare patients with progression compared those without significant progression or no progression.

  18 months

Secondary Outcomes (4)

• Changes of total brain volume and grey matter volume from baseline

  18 months

• Changes of ipsilateral cerebral white matter lesions from baseline (T2-weight lesions, in terms of number and total volumes indexed to the total brain volume)

  18 months

• Changes of the carotid total plaque area and extent of CEUS positive plaques

  18 months

• Compare the esteem of the degree and the characteristics of the main plaque with standard Duplex scan versus CEUS using contrast enhanced carotid CT scan as gold standard

  at baseline

Other Outcomes (1)

• Specific biomarkers (specific T-cell subsets and monocytic subsets and other cytokines) can be associated with WMH and brain atrophy at base line and at follow up (biomarkers to identify progression of WMHs and brain atrophy)

  18 months

Study Arms (1)

Carotid imaging with Visipaque 320 and SonoVue

EXPERIMENTAL

Patients undergo to brain MRI, carotid contrast-enhanced CTA, duplex ultrasound, CEUS, blood sampling, clinical structured interview. Intervention is related to the administration of contrast agents: Visipaque 320 for contrast-enhanced CTA, and SonoVue for CEUS

Drug: Visipaque 320 and SonoVue

Interventions

Visipaque 320 and SonoVue DRUG

Intervention is related to the administration of contrast agents: Iodixanol, 320 mg of iodine per millilitre, Visipaque 320 (GE Healthcare, Milwaukee, WI, USA) for contrast-enahnced CTA, Sodium hexafluoride (SonoVue, Bracco Imaging, Milan, Italy) for CEUS

Also known as: Contrast agents

Carotid imaging with Visipaque 320 and SonoVue

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- bearing an asymptomatic carotid stenosis of 30-70% in diameter, as established by Doppler-measured peak systolic flow velocity, according to the Society of Radiologists in Ultrasound Consensus Conference (Grant et al. Radiology 2003).

You may not qualify if:

• pregnancy or possibility of pregnancy,
• history of allergic diathesis,
• history of stroke or transitory ischemic attack,
• previous carotid artery stenting or carotid endarterectomy,
• history of autoimmune vasculitis,
• History of drug abuse, alcohol abuse or any psychiatric or social condition which may contraindicate the participation to a clinical study
• life expectancy of less than 18 months due to underlying medical conditions,
• presence of cognitive impairment preventing the patient from providing informed consent,
• Atrial fibrillation or previous cardiac surgery or positioning of intracardiac devices (excluded coronary stents) as potential confounding causes of cerebral ischemic damage,
• Known patent foramen ovale (PFO) necessitating anti-platelet treatment
• Current anti-coagulation,
• Previous infections to the central nervous system (CNS)
• Previous surgery to the CNS
• History of anoxic damage to the CNS
• Dementia

Sponsors & Collaborators

• Enrico Ammirati: lead

Related Publications (5)

• Ammirati E, Moroni F, Magnoni M, Rocca MA, Messina R, Anzalone N, De Filippis C, Scotti I, Besana F, Spagnolo P, Rimoldi OE, Chiesa R, Falini A, Filippi M, Camici PG. Relation between characteristics of carotid atherosclerotic plaques and brain white matter hyperintensities in asymptomatic patients. Sci Rep. 2017 Sep 5;7(1):10559. doi: 10.1038/s41598-017-11216-x.

  PMID: 28874779 RESULT

• Ammirati E, Moroni F, Magnoni M, Di Terlizzi S, Villa C, Sizzano F, Palini A, Garlaschelli K, Tripiciano F, Scotti I, Catapano AL, Manfredi AA, Norata GD, Camici PG. Circulating CD14+ and CD14highCD16- classical monocytes are reduced in patients with signs of plaque neovascularization in the carotid artery. Atherosclerosis. 2016 Dec;255:171-178. doi: 10.1016/j.atherosclerosis.2016.10.004. Epub 2016 Oct 6.

  PMID: 27751505 RESULT

• Ammirati E, Magnoni M, Moroni F, Di Terlizzi S, Scotti I, Villa C, Sizzano F, Impellizzeri M, Fanelli G, Esposito G, Chiesa R, Camici PG. Reduction of Circulating HLA-DR+ T Cell Levels Correlates With Increased Carotid Intraplaque Neovascularization and Atherosclerotic Burden. JACC Cardiovasc Imaging. 2016 Oct;9(10):1231-1233. doi: 10.1016/j.jcmg.2015.10.010. Epub 2016 Jan 6. No abstract available.

  PMID: 26777226 RESULT

• Moroni F, Magnoni M, Vergani V, Ammirati E, Camici PG. Fractal analysis of plaque border, a novel method for the quantification of atherosclerotic plaque contour irregularity, is associated with pro-atherogenic plasma lipid profile in subjects with non-obstructive carotid stenoses. PLoS One. 2018 Feb 12;13(2):e0192600. doi: 10.1371/journal.pone.0192600. eCollection 2018.

  PMID: 29432486 RESULT

• Ammirati E, Moroni F, Magnoni M, Rocca MA, Anzalone N, Cacciaguerra L, Di Terlizzi S, Villa C, Sizzano F, Palini A, Scotti I, Besana F, Spagnolo P, Rimoldi OE, Chiesa R, Falini A, Filippi M, Camici PG. Progression of brain white matter hyperintensities in asymptomatic patients with carotid atherosclerotic plaques and no indication for revascularization. Atherosclerosis. 2019 Aug;287:171-178. doi: 10.1016/j.atherosclerosis.2019.04.230. Epub 2019 May 6.

  PMID: 31101367 DERIVED

MeSH Terms

Conditions

Carotid Stenosis; Atherosclerosis; Ischemic Stroke; Carotid Artery Diseases

Interventions

contrast agent BR1; Contrast Media

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Arteriosclerosis; Stroke

Intervention Hierarchy (Ancestors)

Diagnostic Uses of Chemicals; Pharmacologic Actions; Chemical Actions and Uses; Specialty Uses of Chemicals

Study Officials

• Enrico Ammirati, Doctor

  ASST Grande Ospedale Metropolitano Niguarda and Università Vita-Salute San Raffaele; both in Milan, Italy

  PRINCIPAL INVESTIGATOR

• Paolo G Camici, Professor

  Università Vita-Salute San Raffaele and Hospital, Milan, Italy

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator of the grant number GR-2009-1608780 funded by the Italian Ministry of Health Grant

Study Record Dates

• First Submitted: October 30, 2017
• First Posted: November 6, 2017
• Study Start: April 1, 2012
• Primary Completion: October 1, 2017
• Study Completion: October 1, 2017
• Last Updated: February 19, 2018

Record last verified: 2018-02