Clinical trial NCT06046508: Migraine With Aura and Patent Foramen Ovale: Identification of Biomarkers to Select Patients In Whom Intervention Would Be Beneficial (MANET)
Official title: Migraine With Aura and Causal or Incidental Patent Foramen Ovale (PFO): Identification of Biomarker(s) to Select Patients Who Would Most Benefit From PFO Closure. The MANET Study
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Migraine Headache
PFO - Patent Foramen Ovale
Keywords: platelets
prothrombotic platelets phenotype
metabolomics
Lead sponsor: Centro Cardiologico Monzino
Sponsor class: OTHER
Collaborators: name: IRCCS Policlinico S. Donato
name: Università di Cagliari
name: Federico II University
First posted: 2023-09-21
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with MHA, PFO and previous neurological event (TIA or stroke) with clinical indication for percutaneous correction of the defect according to guidelines.

As a control group, 30 subjects without known disease with age \> 18 years will be enrolled.

Brief summary: This is a multicenter prospective observational study aimed to asses whether a specific prothrombotic platelet phenotype can discern migraine patients with PFO (patent forame ovale) - related symptoms from patients with incidental PFO. The study will also explore additional distinguishing features of causal and incidental PFO using a metabolomics approach. It involves the enrollment of well-characterized patient cohorts and an ex vivo approach using comparative cell biology models that reproduce the most critical aspects of the clinical scenario.

Detailed description: Patients with PFO, who meet all the inclusion and none of the exclusion criteria, will be enrolled in the study. Patients will undergo percutaneous correction of PFO and the following evaluations as clinical practice:

* thrombophilic screening (factor V and II and MTHFR gene mutation); sampling for homocysteine, Protein C (Prot C), Protein S (Prot S) and antithrombin III assay;
* anatomic evaluation of the SIA (Saccular intracranial aneurysm) by color-doppler TT echocardiogram and intracardiac ultrasound for definition of the anatomy of the fossa ovalis: tunneled appearance; absence of SIA aneurysm; bulging of the SIA; convex right/left SIA aneurysm;
* quantification of right-left intracardiac shunt by CT doppler;
* classification of migraine according to Anzola scale at baseline visit, post PFO correction, at follow-up at 6 and 12 months.

For the purpose of the study, blood sampling will be performed for evaluation of platelet reactivity; oxidative stress, aggregability, and deformability of red blood cells; and isolation of Endothelial Colony Forming Cells (ECFCs) for analysis of endothelial function. The latter in particular will be evaluated in comparison with the endothelial function of 30 subjects without known disease with age \> 18 years, enrolled as a control group.

All analyses will be performed before PFO correction and 180 days after surgery.

Eligibility criteria: Inclusion Criteria:

* presence of PFO with right-left shunt at baseline \> 10 MES and during Valsalva \> 20 MES
* previous Stroke or TIA
* positive MRI for ischemic outcomes
* SIA aneurysm or residual Chiari/Eustachian valve network
* thrombophilic screening positivity (MTHFR/prot C/prot S)
* cability to sign informed consent for study participation and adherence to planned clinical follow-ups

Exclusion Criteria:

* paroxysmal/refractory atrial fibrillation
* TSA vasculopathy
* left ventricular ejection fraction \<30%
* moderate/severe mitral valve regurgitation
* need for long-term anticoagulant therapy
* allergy or intolerance to antiplatelet therapy
* nickel allergy
* severe chronic kidney disease (GFR \< 30 mL/min)

Primary outcomes:
measure: Number of migraineurs patients with Platelet activation
timeFrame: through study completion, an average of 2 years
measure: Number of migraineurs patients with high Thrombin generation levels
timeFrame: through study completion, an average of 2 years
measure: levels of the oxidative status in PFO patients
timeFrame: through study completion, an average of 2 years
measure: Number of migraineurs patients with Untargeted metabolomics
timeFrame: through study completion, an average of 2 years
Secondary outcomes:
measure: Elucidate whether mechanical stress related to the right-to-left shunt may influence Erythrocyte behavior affecting in turn oxidative stress status
timeFrame: through study completion, an average of 2 years
measure: Assess whether a unique endothelial dysfunction profile identifies migraineurs with incidental PFO
timeFrame: through study completition, an average of 2 years
Other outcomes:
Locations:
city: San Donato Milanese
country: Italy
facility: IRCCS Policlinico San Donato
state: Milan
city: Cagliari
country: Italy
facility: Università di Cagliari
city: Napoli
country: Italy
facility: Azienda Ospedaliera Universitaria "Federico II"
Study officials:
affiliation: IRCCS Centro Cardiologico Monzino
name: Daniela Trabattoni, MD
role: PRINCIPAL_INVESTIGATOR
References: