Potential Impact of Neuroimmune and Autophagic Alterations on the Progression and Severity of Human Atherosclerotic Process

The hypothesis of this study is that neural regulations of the atherosclerotic plaque, identified in the murine model of atherosclerosis, could also exist in human pathology. The dysregulation status of the autonomic nervous system is typical of several cardiovascular diseases, but the role it exerts in the modulation of important mechanisms at the basis of the atherosclerotic process progression has not been investigated yet. The main aim of this study will be to investigate, in the atherosclerotic plaque, the alterations of inflammatory and immune processes, the neural modulations and the presence of dysregulations of the autophagic process. The investigators will also associate the potential presence of neural modulations of the plaque to its stability/instability, from a clinical-translational point of view. Finally, the investigators aim at providing a solid basis for the development of novel therapeutic strategies, which could reduce the elevated health and welfare costs for the clinical management of cardiovascular pathologies such as atherosclerosis.

Study Overview

• Status: Recruiting
• Conditions: Carotid Atherosclerosis
• Intervention / Treatment: Other: No interventions

• Study Type: Observational
• Enrollment (Anticipated): 50

Contacts and Locations

• Study Contact: Name: Giuseppe Lembo, MD, PhD; Phone Number: +39 0865915225; Email: lembo@neuromed.it

Study Locations

• Italy
  • Pozzilli, Italy, 86077
    • Recruiting
    • IRCCS Neuromed
    • Contact: Giuseppe Lembo, MD, PhD; Phone Number: +39 0865915225
    • Principal Investigator: Giuseppe Lembo, MD, PhD
    • Principal Investigator: Giacomo Frati, MD, PhD
    • Sub-Investigator: Francesco Pompeo, MD
    • Sub-Investigator: Alessandro Landolfi, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Subjects will be selected from patients who will undergo to surgical intervention of carotid trombo-endo-arterectomy at the Department of Vascular Surgery of the IRCCS Neuromed, accordingly to the following inclusion/exclusion criteria. Approximately 50 subjects of both genders will be included in the study.

Description

Inclusion Criteria:

• age ≥ 45 and ≤ 90 years;
• patients with severe (70-99%) carotid stenosis, diagnosed with color doppler echography or angio-MRI or angiography;
• written informed consent.

Exclusion Criteria:

• carotid stenosis <70% at carotid bifurcation or diagnosed with color doppler echography or angio-MRI or angiography;
• severe neoplasia;
• participation to other clinical trial, ongoing or terminated less than one month before enrolment in this study.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Case Group; Patients who undergo surgical intervention of carotid trombo-endo-arterectomy at the Department of Vascular Surgery of the IRCCS Neuromed, with specific inclusion/exclusion criteria	Other: No interventions; No interventions - observational study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Characterization of the neuro-modulation of immune system in atherosclerosis	Immunohistochemistry and immunofluorescence of the autonomic nervous and immune systems in the atherosclerotic plaque, and flow cytometry analysis of circulating immune cells.	At enrollment
Characterization of the autophagic process and correlation with neural modulations of the stability/instability plaque	Expression of autophagic markers and immunohistochemical analysis of the atherosclerotic plaque.	At enrollment

Collaborators and Investigators

• Sponsor: Neuromed IRCCS
• Investigators: Principal Investigator: Giuseppe Lembo, MD, PhD, IRCCS Neuromed; Principal Investigator: Giacomo Frati, MD, PhD, IRCCS Neuromed

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2019
• Primary Completion (Anticipated): June 30, 2022
• Study Completion (Anticipated): June 30, 2022

Study Registration Dates

• First Submitted: April 17, 2019
• First Submitted That Met QC Criteria: April 17, 2019
• First Posted (Actual): April 22, 2019

Study Record Updates

• Last Update Posted (Actual): April 11, 2022
• Last Update Submitted That Met QC Criteria: April 8, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: autonomic nervous system; immune system; autophagy; atherosclerotic plaque
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Carotid Artery Diseases; Atherosclerosis
• Other Study ID Numbers: LMB06

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No