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

Official title

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

Overview

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.

Interventions

• 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

Primary outcome measures

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

Secondary outcome measures (4)

• 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 [Time frame: 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 [Time frame: 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 [Time frame: Through study completion, an average of 2 years and six months]
• Definition of the prevalence of pathogenic variants in other genes [Time frame: Through study completion, an average of 2 years and six months]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Diagnostic

Study locations

Italy · 1 center

• Fondazione Policlinico Universitario A. Gemelli IRCCS — Rome

Identifiers

NCT: NCT06862063 · 6813

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗