Migraine With Aura and Patent Foramen Ovale: Identification of Biomarkers to Select Patients In Whom Intervention Would Be Beneficial (MANET)

Migraine Headache Clinical Trial

— 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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06046508
• Other study ID #: CCM 1934
• Status: Recruiting
• Start date: May 18, 2023
• Est. completion date: April 2025

Study information

• Verified date: September 2023
• Source: Centro Cardiologico Monzino
• Contact: Daniela Trabattoni, MD
• Phone: 0285800
• Email: daniela.trabattoni[@]cardiologicomonzino.it
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: April 2025
• Est. primary completion date: April 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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)

Related Conditions & MeSH terms

• Foramen Ovale, Patent
• Headache
• Migraine Disorders
• Migraine Headache
• Migraine with Aura
• PFO - Patent Foramen Ovale

Intervention

Other:
• blood samples collection
patients, who meet all the inclusion criteria and none of the exclusion criteria, will be enrolled and they will perform a blood withdrawal before PFO correction and 180 days after the intervention

Locations

Country	Name	City	State
Italy	Università di Cagliari	Cagliari
Italy	Azienda Ospedaliera Universitaria "Federico II"	Napoli
Italy	IRCCS Policlinico San Donato	San Donato Milanese	Milan

Sponsors (4)

Lead Sponsor	Collaborator
Centro Cardiologico Monzino	Federico II University, IRCCS Policlinico S. Donato, Università di Cagliari

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of migraineurs patients with Platelet activation	Fresh whole blood will be stained for tissue factor (TF) expression, platelet activation markers [P-selectin and activated glycoprotein IIbIIIa] and annexinV binding to phosphatidylserine (PS). Flow cytometry analysis will be performed on fixed samples. Platelet procoagulant potential will be assessed by thrombin generation assay. The CAT assay (Chloramphenico Acetyltransferase) lwill be performed in the presence of a neutralizing anti-Tisse Factor (aTF) antibody (Ab) to assess the contribution of TF, and by adding an excess of exogenous phospholipids.	through study completion, an average of 2 years
Primary	Number of migraineurs patients with high Thrombin generation levels	Flow cytometry MV characterization will be performed on stored patients' plasma samples. On the same plasma samples, MV procoagulant potential will be assessed by thrombin generation assay.	through study completion, an average of 2 years
Primary	levels of the oxidative status in PFO patients	RBC (red blood cells) deformability and aggregability, generation of oxygen radicals in RBC and platelets of the overall enrolled population will be analyzed at T0 and at T1. Systemic redox status will be quantified by evaluating concentrations of both reduced glutathione (GSH) and its oxidized form GSSG (oxidized glutathione) on stored samples.	through study completion, an average of 2 years
Primary	Number of migraineurs patients with Untargeted metabolomics	The metabolomic patterns of plasma, urine and platelets/ECFC (endothelial-colony forming cells) of the enrolled population will be investigated by a combined use of spectroscopy and multivariate and univariate statistical tools in order to identify the molecular fingerprint that could build a score able to identify patients with incidental PFO.	through study completion, an average of 2 years
Secondary	Elucidate whether mechanical stress related to the right-to-left shunt may influence Erythrocyte behavior affecting in turn oxidative stress status	This will be accomplished ex vivo by using a microfluidic platform that recapitulates the specific shear stress profiles to which blood is exposed as it flows through the PFO	through study completion, an average of 2 years
Secondary	Assess whether a unique endothelial dysfunction profile identifies migraineurs with incidental PFO	Functional profiling will be carried out, by measuring proliferation, migration and in vitro angiogenesis. The pro-inflammatory and pro-thrombotic phenotype of the cells will be assessed using a panel of molecular markers. Platelet adhesion will be determined on resting and activated ECFC under flow conditions; thrombin generation will be measured using a cell-based assay.	through study completition, an average of 2 years