Next Generation Sequencing Analysis of Patients with Spontaneous Dissection of Cervical Arteries (NASCeAD)

Next Generation Sequencing (NGS) Analysis of Patients with Spontaneous Dissection of Cervical Arteries (sCeAD), a Multi-centric, Interventional, Cohort Study

The goal of this observational study is to analyze the existence of a genetic predisposition in patients with spontaneous dissections of the cervical arteries (SCeAD).

The main questions it aims to answer are:

1. Which is the prevalence of pathogenic variants in genes coding for proteins involved in the structure or function of the connective tissue in adult patients with spontaneous dissections of the cervical arteries?
2. Which are the clinical characteristics of each single genetic variant identified?
3. Which are the clinical, radiological, laboratory variables associated with the finding of a pathogenic variant?
4. Are there differences between patients with SCeAD who have a pathogenic variant in a gene coding for proteins involved in the structure or function of the connective tissue and those who not?
5. There are differences in the risk of SCeAD recurrence between patients with SCeAD who have a pathogenic variant in a gene coding for proteins involved in the structure or function of the connective tissue and those who not?
6. There are differences in the risk of SCeAD recurrence based on the specific typology of genetic variant found?

Participants will be asked to undergo:

• a whole-CT total-body with contrast;
• a dysmorphological visit;
• a blood sampling for genetic testing;
• a neurological visit;
• Some follow-up visits.

Study Overview

• Status: Recruiting
• Conditions: Dissection Carotid Artery; Dissecting Aneurysm; Dissection Arterial
• Intervention / Treatment: Diagnostic test: Genetic testing

• Study Type: Interventional
• Enrollment (Estimated): 145
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Giovanni Frisullo, MD, PhD; Phone Number: +390630156321; Email: giovanni.frisullo@policlinicogemmelli.it
• Study Contact Backup: Name: Irene Scala, MD; Phone Number: +390630156321; Email: irene.scala@guest.policlinicogemelli.it

Study Locations

• Italy
  • Lazio
    • Roma, Lazio, Italy, 00168
      • Recruiting
      • Fondazione Policlinico Universitario A. Gemelli IRCCS
      • Contact: Giovanni Frisullo; Phone Number: +390630156321

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adult age (≥18 years);
• Presence of a dissection of one or more cervical arteries (carotid or vertebrobasilar district), defined as the finding, on an appropriate radiological examination (CT and/or MRI of the neck and brain district with/without contrast medium and/or digital subtraction angiography and/or echocolordoppler of the epiaortic vessels) of "intramural hematoma, pseudoaneurysmal dilation, intimal flap, double lumen, long tapering stenosis or occlusion ≥2 cm above the carotid bifurcation with finding of an aneurysmal dilation or a long tapering stenosis after recanalization of the vessel";

• At least one or more of the following criteria:

  • Radiological evidence on CT and/or MRI with/without contrast and/or digital subtraction angiography and/or color Doppler ultrasound of vessel wall anomalies (such as aneurysms, dissections, tortuosity, ectasia or vascular stenosis) in one or more vascular districts in addition to that of the known dissection;

  • Family history of:

    • vessel dissections and/or sudden death and/or cerebrovascular or cardiovascular diseases at a young age;
    • spontaneous perforation of internal organs and/or dehiscence and/or laxity of connective tissue (spontaneous prolapses);
  • dysmorphological abnormalities at the clinical examination (including Beighton score ≥5 or Marfan score ≥7), laboratory and/or radiological findings suggestive of connective tissue disease or other genetic condition known to be associated with the development of aneurysms or alterations of the vessel wall;
• Written informed consent

Exclusion Criteria:

• Recent history of trauma clearly related in type, location and dynamics to the development of dissection;
• Iatrogenic dissection following endovascular procedure;
• Exclusively intracranial dissection;
• Fibromuscular dysplasia.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Adult patients with spontaneous dissections of the Cervical arteries	Diagnostic test: Genetic testing; Each eligible patient will undergo a blood sample to perform a genetic analysis through Next Generation Sequencing (NGS) technique in order to analyze a high number of genes involved in the structure/function of connective tissue; Other Names: Next generation sequencing analysis of an extended panel of genes

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Definition of the percentage prevalence (n - %) of pathogenic variants in patients with Spontaneous Cervical Artery Dissection (SCeAD)	To define the percentage prevalence (n - %) of pathogenic variants of genes encoding proteins involved in the structure/function of connective tissue in patients with spontaneous dissection of the cervical arteries	Through study completion, an average of 2 years and six months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of the percentage prevalence (n - %) of each pathogenic variant in genes encoding connective tissue proteins in patients with spontaneous dissection of the cervical arteries	Description of the typology and percentage prevalence (n - %) of individual pathogenic variants of genes encoding proteins involved in the structure/function of connective tissue in patients with spontaneous dissections of the Cervical arteries	Through study completion, an average of 2 years and six months
Identification of clinical predictors of pathogenic variants in genes encoding connective tissue proteins in patients with spontaneous cervical artery dissection	Percentage prevalence (n - %) of clinical predictors of pathogenic variants in genes encoding proteins involved in the structure/function of connective tissue in patients with spontaneous dissection of the cervical arteries through multivariable regression models. In particular, clinical (eg. Beighton score, Marfan score, symptoms that lead to the finding of the dissection, etc), radiological (eg. the presence of vascular abnormalities in other vascular districts, the aspect of the cervical artery dissection at the US, CT, or MRI examination, etc.), and laboratory parameters (eg. hyperhomocisteinemia, immunological screening, CRP, etc.) will be compared between patients with spontaneous dissections of the cervical arteries who have a pthogenic variant of genes encoding for connective tissue proteins and those who not.	Through study completion, an average of 2 years and six months
Assessment of the risk of artery dissection recurrence in patients with spontaneous cervical artery dissection carrying a pathogenic variant in those without through the ODD ratio	Comparison of the risk of recurrence of vascular dissections in the cervical arteries or in other vascular districts in patients with spontaneous cervical artery dissection carrying a pathogenic variant in genes encoding proteins involved in connective tissue structure/function and in those without it by calculating the ODD ratio	Through study completion, an average of 2 years and six months
Definition of the prevalence of pathogenic variants in other genes	Percentage prevalence (n - %) of individual pathogenic variants of genes encoding proteins not involved in the structure/function of connective tissue in patients with spontaneous dissection of the cervical arteries and correlation of the same with individual clinical phenotypes;	Through study completion, an average of 2 years and six months

Collaborators and Investigators

• Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
• Collaborators: University of Rome Tor Vergata; Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta; I.R.C.C.S. Fondazione Santa Lucia; Istituto Clinico Humanitas; Azienda Policlinico Umberto I; San Camillo Hospital, Rome; Santo Spirito Hospital, Italy; Istituto Neurologico Mediterraneo Neuromed S. R. L; Ospedale V. Fazzi; Istituto Neurologico Nazionale IRCCS Casimiro Mondino, Pavia, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna; Ospedale Policlinico San Martino, Genova; Azienda Ospedaliera di Rilievo Nazionale A.Cardarelli; Ospedale Guzzardi di Vittoria

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2024
• Primary Completion (Estimated): December 1, 2030
• Study Completion (Estimated): December 1, 2030

Study Registration Dates

• First Submitted: November 14, 2024
• First Submitted That Met QC Criteria: March 2, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 2, 2025
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Dissection, Blood Vessel; Acute Aortic Syndrome; Vascular Diseases; Cardiovascular Diseases; Aortic Diseases; Aneurysm; Aortic Dissection
• Other Study ID Numbers: 6813

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There are not plans to make IPD available to other researchers as we will be dealing with highly sensitive data, such as genetic data.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No