Lectine Pathway in Unstable Carotid Plaque
July 22, 2020 updated by: Angela M.R. Ferrante, Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Evaluation of Lectine Pathway in Assessment of Unstable Carotid Plaque
The study is aimed to investigate the possible role of lectin pathway - an alternative pathway of complement activation - in affecting stability of carotid atherosclerotic plaques and the possible correlations with clinical neurologic features.
Study Overview
Status
Withdrawn
Intervention / Treatment
Detailed Description
In addition to the known hemodynamic criteria, instable carotid plaques can be responsible for brain ischemia, therefore is paramount to identify preoperatively possible markers of plaque instability.
The study is aimed to investigate the possible role of lectin pathway - an alternative pathway of complement activation - in affecting stability of carotid atherosclerotic plaques and the possible correlations with clinical neurologic features.
Study population will include 40 patients with internal carotid artery stenosis >=70% (assessed by echocolordoppler), symptomatic or asymptomatic, surgically treated by endoarterectomy.
Removed plaques will be evaluated by histologic exam and immunofluorescence for ficolins 1-2-3 and Mannose Binding Lectin (MBL).
Plasma samples will be used for ELISA test of lectin pathway complement activation.
Study Type
Observational
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
40 years to 80 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Sampling Method
Non-Probability Sample
Study Population
Study population will include 40 patients with symptomatic or asymptomatic internal carotid artery stenosis >=70% (measured by echocolordoppler) treated by elective or urgent endoarterectomy.
Description
Inclusion Criteria:
- patients undergone elective or urgent carotid endoarterectomy (CEA) for internal carotid stenosis >70% (assessed by velocimetric criteria) with or without neurologic symptoms
Exclusion Criteria:
- recent (<20 days) major/minor stroke with positive CT scan
- absolute contraindications to surgery (cardiac, respiratory, anesthesiologic risk)
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Observational Models: Cohort
- Time Perspectives: Prospective
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
|---|---|
|
asymptomatic
asymptomatic patients undergoing carotid endoarterectomy for stenosis >70% (velocimetric criteria at echodoppler)
|
Surgical removal of carotid bifurcation plaque and arterial repair (direct suture or patch)
Other Names:
|
|
symptomatic
symptomatic (TIA, crescendo TIA, minor stroke) patients undergoing carotid endoarterectomy, independently from stenosis evaluated by echodoppler
|
Surgical removal of carotid bifurcation plaque and arterial repair (direct suture or patch)
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
lectine pathway of complement activation in carotid plaques
Time Frame: preoperative
|
assessment of association between plasmatic levels of complement activators and plaque instability (histologic index).
Protein plasma levels will be assessed as optical density.
Plaque instability will be quantified by a vulnerability score that combines four different histological parameters according to their quartile distribution (Fumagalli et al., Frontiers Immunology 2017).
Their association will be analyzed as odds ratio (95%-CI) by a Fisher test.
|
preoperative
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
focal neurologic symptoms and plasmatic levels of complement activators
Time Frame: preoperative, postoperative day 3, 3 months after surgery
|
Correlation of onset of focal neurologic symptoms (TIA, any stroke) due to carotid stenosis and peripheral plasma levels of complement activators.
Neurological exam + CT or MNR will be used as clinical measurement tool
|
preoperative, postoperative day 3, 3 months after surgery
|
|
focal neurologic symptoms and histologic index of plaque instability
Time Frame: through study completion (average 1 year)
|
correlation of onset of focal neurologic symptoms (TIA, any stroke) due to carotid stenosis and histologic index for plaque instability.
Protein plasma levels will be assessed as optical density.
Plaque instability will be quantified by a vulnerability score that combines four different histological parameters according to their quartile distribution (Fumagalli et al., Frontiers Immunology 2017).
|
through study completion (average 1 year)
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Investigators
- Principal Investigator: Angela MR Ferrante, MD, Fondazione Policlinico Universitario A.Gemelli IRCCS Roma
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- Verhoeven B, Hellings WE, Moll FL, de Vries JP, de Kleijn DP, de Bruin P, Busser E, Schoneveld AH, Pasterkamp G. Carotid atherosclerotic plaques in patients with transient ischemic attacks and stroke have unstable characteristics compared with plaques in asymptomatic and amaurosis fugax patients. J Vasc Surg. 2005 Dec;42(6):1075-81. doi: 10.1016/j.jvs.2005.08.009.
- Longhi L, Orsini F, De Blasio D, Fumagalli S, Ortolano F, Locatelli M, Stocchetti N, De Simoni MG. Mannose-binding lectin is expressed after clinical and experimental traumatic brain injury and its deletion is protective. Crit Care Med. 2014 Aug;42(8):1910-8. doi: 10.1097/CCM.0000000000000399.
- Fust G, Munthe-Fog L, Illes Z, Szeplaki G, Molnar T, Pusch G, Hirschberg K, Szegedi R, Szeplaki Z, Prohaszka Z, Skjoedt MO, Garred P. Low ficolin-3 levels in early follow-up serum samples are associated with the severity and unfavorable outcome of acute ischemic stroke. J Neuroinflammation. 2011 Dec 29;8:185. doi: 10.1186/1742-2094-8-185.
- Osthoff M, Katan M, Fluri F, Schuetz P, Bingisser R, Kappos L, Steck AJ, Engelter ST, Mueller B, Christ-Crain M, Trendelenburg M. Mannose-binding lectin deficiency is associated with smaller infarction size and favorable outcome in ischemic stroke patients. PLoS One. 2011;6(6):e21338. doi: 10.1371/journal.pone.0021338. Epub 2011 Jun 21.
- Zangari R, Zanier ER, Torgano G, Bersano A, Beretta S, Beghi E, Casolla B, Checcarelli N, Lanfranconi S, Maino A, Mandelli C, Micieli G, Orzi F, Picetti E, Silvestrini M, Stocchetti N, Zecca B, Garred P, De Simoni MG; LEPAS group. Early ficolin-1 is a sensitive prognostic marker for functional outcome in ischemic stroke. J Neuroinflammation. 2016 Jan 20;13:16. doi: 10.1186/s12974-016-0481-2.
- Pilely K, Fumagalli S, Rosbjerg A, Genster N, Skjoedt MO, Perego C, Ferrante AMR, De Simoni MG, Garred P. C-Reactive Protein Binds to Cholesterol Crystals and Co-Localizes with the Terminal Complement Complex in Human Atherosclerotic Plaques. Front Immunol. 2017 Aug 29;8:1040. doi: 10.3389/fimmu.2017.01040. eCollection 2017.
- Hellings WE, Pasterkamp G, Vollebregt A, Seldenrijk CA, De Vries JP, Velema E, De Kleijn DP, Moll FL. Intraobserver and interobserver variability and spatial differences in histologic examination of carotid endarterectomy specimens. J Vasc Surg. 2007 Dec;46(6):1147-54. doi: 10.1016/j.jvs.2007.08.018. Epub 2007 Oct 22.
- Fumagalli S, Perego C, Zangari R, De Blasio D, Oggioni M, De Nigris F, Snider F, Garred P, Ferrante AM, De Simoni MG. Lectin Pathway of Complement Activation Is Associated with Vulnerability of Atherosclerotic Plaques. Front Immunol. 2017 Mar 16;8:288. doi: 10.3389/fimmu.2017.00288. eCollection 2017.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Anticipated)
April 1, 2019
Primary Completion (Anticipated)
January 31, 2021
Study Completion (Anticipated)
February 28, 2021
Study Registration Dates
First Submitted
January 7, 2019
First Submitted That Met QC Criteria
January 26, 2019
First Posted (Actual)
January 30, 2019
Study Record Updates
Last Update Posted (Actual)
July 24, 2020
Last Update Submitted That Met QC Criteria
July 22, 2020
Last Verified
July 1, 2020
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2124
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
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