Lectine Pathway in Unstable Carotid Plaque

Carotid Artery Plaque Clinical Trial

Official title:

Evaluation of Lectine Pathway in Assessment of Unstable Carotid Plaque

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT03822195
• Other study ID #: 2124
• Status: Withdrawn
• Start date: April 1, 2019
• Est. completion date: February 28, 2021

Study information

• Verified date: July 2020
• Source: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: February 28, 2021
• Est. primary completion date: January 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 80 Years

Eligibility

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)

Related Conditions & MeSH terms

• Carotid Artery Plaque
• Carotid Stenosis
• Mannose-Binding Lectin Complement Pathway

Intervention

Procedure:
• Carotid endoarterectomy
Surgical removal of carotid bifurcation plaque and arterial repair (direct suture or patch)

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Fondazione Policlinico Universitario Agostino Gemelli IRCCS

References & Publications (8)

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. do — View Citation

Füst G, Munthe-Fog L, Illes Z, Széplaki G, Molnar T, Pusch G, Hirschberg K, Szegedi R, Széplaki Z, Prohászka 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. — View Citation

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. Epub 2007 Oct 22. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	lectine pathway of complement activation in carotid plaques	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	focal neurologic symptoms and plasmatic levels of complement activators	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
Secondary	focal neurologic symptoms and histologic index of plaque instability	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)