Next Generation Sequencing Analysis of Patients with Spontaneous Dissection of Cervical Arteries

Not Applicable

Recruiting

• Conditions: Dissection Carotid Artery; Dissection Arterial; Dissecting Aneurysm

• Registration Number: NCT06862063
• Lead Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2024-11
• Study First Submitted: 2024-11-14
• Study Start: 2024-12-01
• Study First Submitted QC: 2025-03-02
• Last Update Submitted: 2025-03-02
• Study First Posted: 2025-03-06
• Last Update Posted: 2025-03-06
• Primary Completion: 2030-12-01
• Study Completion: 2030-12-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 145

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Definition of the percentage prevalence (n - %) of pathogenic variants in patients with Spontaneous Cervical Artery Dissection (SCeAD)	Through study completion, an average of 2 years and six months	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

Secondary Outcome Measures

Name	Time	Method
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	Through study completion, an average of 2 years and six months	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
Identification of clinical predictors of pathogenic variants in genes encoding connective tissue proteins in patients with spontaneous cervical artery dissection	Through study completion, an average of 2 years and six months	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.
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	Through study completion, an average of 2 years and six months	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
Definition of the prevalence of pathogenic variants in other genes	Through study completion, an average of 2 years and six months	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;

Trial Locations

Locations (1)

Fondazione Policlinico Universitario A. Gemelli IRCCS; 🇮🇹 Roma, Lazio, Italy