Carotid Artery PlaqueNCT03822195
Lectine Pathway in Unstable Carotid Plaque
An observational study of Carotid Artery Plaque and Mannose-Binding Lectin Complement Pathway, run by Fondazione Policlinico Universitario Agostino Gemelli IRCCS.
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. Read more about this study
- Who is it for?
- Ages 40 to 80 years
- Conditions the study is for
- Carotid Artery Plaque, Mannose-Binding Lectin Complement Pathway
- What is being tested?
- Carotid endoarterectomy
- Type of treatment
- Surgery or procedure
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 1 Apr 2019to 28 Feb 2021
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- patients undergone elective or urgent carotid endoarterectomy (CEA) for internal carotid stenosis >70% (assessed by velocimetric criteria) with or without neurologic symptoms
Who cannot join
- recent (<20 days) major/minor stroke with positive CT scan
- absolute contraindications to surgery (cardiac, respiratory, anesthesiologic risk)
About this study
Official title: 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.
Read the 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.
- Being tested
- Carotid endoarterectomy
- Keywords
- carotid artery atherosclerosis, alternative complement pathway
- Medical subject headings
- Carotid Stenosis, Carotid Artery Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Carotid endoarterectomyProcedure or surgery
Also called CEA
Surgical removal of carotid bifurcation plaque and arterial repair (direct suture or patch)
| Study group | Role | What they receive |
|---|---|---|
| asymptomatic | asymptomatic patients undergoing carotid endoarterectomy for stenosis >70% (velocimetric criteria at echodoppler) Receives: Procedure: Carotid endoarterectomy | |
| symptomatic | symptomatic (TIA, crescendo TIA, minor stroke) patients undergoing carotid endoarterectomy, independently from stenosis evaluated by echodoppler Receives: Procedure: Carotid endoarterectomy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: preoperative
Secondary outcomes (2)
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
Measured: preoperative, postoperative day 3, 3 months after surgery
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).
Measured: through study completion (average 1 year)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2019
- Study start1 Apr 2019 (estimated)
- Primary completion31 Jan 2021 (estimated)
- Study completion28 Feb 2021 (estimated)
Why it stopped: PI changed Institution
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Carotid Artery PlaqueStudies of the same condition, open and under way.
- More trials run by Fondazione Policlinico Universitario Agostino Gemelli IRCCSThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Angela M.R. Ferrante, Fondazione Policlinico Universitario Agostino Gemelli IRCCS
- Investigators
- Angela MR Ferrante, MD, Principal investigator, Fondazione Policlinico Universitario A.Gemelli IRCCS Roma
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03822195
- Sponsor's protocol ID
- 2124
- Status last verified
- Jul 2020
- First submitted
- 7 Jan 2019
- Last updated
- 24 Jul 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
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.
PubMed 16376194Longhi 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.
PubMed 24810526Fust 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.
PubMed 22206485Osthoff 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.
PubMed 21712986Zangari 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.
PubMed 26792363Pilely 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.
PubMed 28900428Hellings 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.
PubMed 17950565Fumagalli 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.
PubMed 28360913
Study at a glance
From the registry record, last updated by the sponsor on 24 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Lectine Pathway in Assessment of Unstable Carotid Plaque
- ClinicalTrials.gov ID
- NCT03822195
- Acronym / sponsor ID
- 2124
- Keywords
- carotid artery atherosclerosis, alternative complement pathway
- Study type
- Observational
- Recruitment status
- WithdrawnReason stopped: PI changed Institution
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Fondazione Policlinico Universitario Agostino Gemelli IRCCSUniversity, hospital or other
- Study start
- 1 Apr 2019 (estimated)
- Primary completion
- 31 Jan 2021 (estimated)
- Study completion
- 28 Feb 2021 (estimated)
- First posted
- 30 Jan 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| asymptomatic | – | Procedure: Carotid endoarterectomyasymptomatic patients undergoing carotid endoarterectomy for stenosis >70% (velocimetric criteria at echodoppler) |
| symptomatic | – | Procedure: Carotid endoarterectomysymptomatic (TIA, crescendo TIA, minor stroke) patients undergoing carotid endoarterectomy, independently from stenosis evaluated by echodoppler |
Who may qualify
- Ages
- 40 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (1 listed)
- patients undergone elective or urgent carotid endoarterectomy (CEA) for internal carotid stenosis >70% (assessed by velocimetric criteria) with or without neurologic symptoms
Key exclusion criteria (2 listed)
- recent (<20 days) major/minor stroke with positive CT scan
- absolute contraindications to surgery (cardiac, respiratory, anesthesiologic risk)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Carotid endoarterectomyAlso: CEASurgical removal of carotid bifurcation plaque and arterial repair (direct suture or patch) | Procedure or surgery | asymptomatic, symptomatic |
Primary outcome
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.
2 secondary outcomes
focal neurologic symptoms and plasmatic levels of complement activators
Time frame: 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)
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jul 2020.
- Background: PubMed 16376194Verhoeven 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.
- Background: PubMed 24810526Longhi 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.
- Background: PubMed 22206485Fust 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.
- Background: PubMed 21712986Osthoff 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.
- Background: PubMed 26792363Zangari 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.
- Background: PubMed 28900428Pilely 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.
- Background: PubMed 17950565Hellings 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.
- Results publication: PubMed 28360913Fumagalli 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Angela MR Ferrante, MD principal investigator
Fondazione Policlinico Universitario A.Gemelli IRCCS Roma
Questions about this trial
What is this clinical trial studying?
An observational study of Carotid Artery Plaque and Mannose-Binding Lectin Complement Pathway, run by Fondazione Policlinico Universitario Agostino Gemelli IRCCS.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 24 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
lectine pathway of complement activation in carotid plaques (time frame: preoperative). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03822195, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jul 2020.