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

February 6, 2024 updated by: Centro Cardiologico Monzino

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Observational

Enrollment (Estimated)

120

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Italy
      • Cagliari, Italy, 09124
        • Active, not recruiting
        • Università di Cagliari
      • Napoli, Italy, 80131
        • Not yet recruiting
        • Azienda Ospedaliera Universitaria "Federico II"
        • Contact:
    • Milan
      • San Donato Milanese, Milan, Italy, 20097

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

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.

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Sigle arm study
Patients with migraine headache with aura (MHA), patent foramen ovale (PFO) and previous neurological event (transient ischemic attack -TIA- or stroke) with clinical indication for percutaneous correction of the defect according to guidelines will be enrolled
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of migraineurs patients with Platelet activation
Time Frame: through study completion, an average of 2 years
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
Number of migraineurs patients with high Thrombin generation levels
Time Frame: through study completion, an average of 2 years
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
levels of the oxidative status in PFO patients
Time Frame: through study completion, an average of 2 years
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
Number of migraineurs patients with Untargeted metabolomics
Time Frame: through study completion, an average of 2 years
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Elucidate whether mechanical stress related to the right-to-left shunt may influence Erythrocyte behavior affecting in turn oxidative stress status
Time Frame: through study completion, an average of 2 years
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
Assess whether a unique endothelial dysfunction profile identifies migraineurs with incidental PFO
Time Frame: through study completition, an average of 2 years
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Centro Cardiologico Monzino

Collaborators

Federico II University
IRCCS Policlinico S. Donato
Università di Cagliari

Investigators

  • Principal Investigator: Daniela Trabattoni, MD, IRCCS Centro Cardiologico Monzino

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 18, 2023

Primary Completion (Estimated)

April 1, 2025

Study Completion (Estimated)

April 1, 2025

Study Registration Dates

First Submitted

August 21, 2023

First Submitted That Met QC Criteria

September 12, 2023

First Posted (Actual)

September 21, 2023

Study Record Updates

Last Update Posted (Actual)

February 8, 2024

Last Update Submitted That Met QC Criteria

February 6, 2024

Last Verified

September 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CCM 1934

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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