Lectine Pathway in Unstable Carotid Plaque

NCT03822195 | Withdrawn

• 1 other identifier: 2124
• Study Type: observational
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Carotid Artery Plaque; Mannose-Binding Lectin Complement Pathway

Keywords

carotid artery atherosclerosis; alternative complement pathway

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• focal neurologic symptoms and plasmatic levels of complement activators

  preoperative, postoperative day 3, 3 months after surgery

• focal neurologic symptoms and histologic index of plaque instability

  through study completion (average 1 year)

Study Arms (2)

asymptomatic

asymptomatic patients undergoing carotid endoarterectomy for stenosis \>70% (velocimetric criteria at echodoppler)

Procedure: Carotid endoarterectomy

symptomatic

symptomatic (TIA, crescendo TIA, minor stroke) patients undergoing carotid endoarterectomy, independently from stenosis evaluated by echodoppler

Procedure: Carotid endoarterectomy

Interventions

Carotid endoarterectomy PROCEDURE

Surgical removal of carotid bifurcation plaque and arterial repair (direct suture or patch)

Also known as: CEA

asymptomatic; symptomatic

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• patients undergone elective or urgent carotid endoarterectomy (CEA) for internal carotid stenosis \>70% (assessed by velocimetric criteria) with or without neurologic symptoms

You may not qualify if:

• recent (\<20 days) major/minor stroke with positive CT scan
• absolute contraindications to surgery (cardiac, respiratory, anesthesiologic risk)

Sponsors & Collaborators

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS: lead

Related Publications (8)

• 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.

  PMID: 16376194 BACKGROUND

• 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.

  PMID: 24810526 BACKGROUND

• 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.

  PMID: 22206485 BACKGROUND

• 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.

  PMID: 21712986 BACKGROUND

• 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.

  PMID: 26792363 BACKGROUND

• 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.

  PMID: 28900428 BACKGROUND

• 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.

  PMID: 17950565 BACKGROUND

• 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.

  PMID: 28360913 RESULT

Biospecimen

Retention: SAMPLES WITH DNA

Atherosclerotic plaque surgically removed from the carotid bifurcation Peripheral blood sample

MeSH Terms

Conditions

Carotid Stenosis; Carotid Artery Diseases

Condition Hierarchy (Ancestors)

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

Study Officials

• Angela MR Ferrante, MD

  Fondazione Policlinico Universitario A.Gemelli IRCCS Roma

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Angela M.R. Ferrante MD PhD

Study Record Dates

• First Submitted: January 7, 2019
• First Posted: January 30, 2019
• Study Start: April 1, 2019
• Primary Completion: January 31, 2021
• Study Completion: February 28, 2021
• Last Updated: July 24, 2020

Record last verified: 2020-07