pLatelEts And MigRaine iN patEnt foRamen Ovale (LEARNER)

Centro Cardiologico Monzino

Status: Completed

Conditions: Migraine With Aura; Platelet Aggregation, Spontaneous; Patent Foramen Ovale

Treatments: Device: patent foramen ovale closure

Study type: Interventional

Funder types: Other

Identifiers

NCT03521193

CCM769

Details and patient eligibility

About

Migraine is a common, chronic neurovascular disorder characterized by attacks of severe headache, autonomic nervous system dysfunction and, in some patients, aura, and disabling neurological symptoms. Worldwide, migraine prevalence is as high as 18% in the general population. Increased frequency of patent foramen ovale (PFO) in migraineurs was first reported in 1998 in a case-control study. Since then, others have described a 60% prevalence of PFO in patients suffering from migraine with aura. The presence of a right-to-left shunt (RLS) is thought to be a potent trigger of migraine attacks, although the mechanism is unknown. Moreover, PFO closure has correlated with improved migraine symptoms in several retrospective uncontrolled studies. The aim of this single-center, prospective study is to assess the impact of PFO closure on migraine attacks over time together with evaluation of potential predictive risk factors.

Full description

The Study will evaluate the results of approximately 100 subjects from a single center study registered in this trial. Subjects who experienced transient ischemic attack (TIA) or stroke with a clinical indication to PFO closure and symptomatic for migraine with/o aura are considered for a migraine score analysis at baseline before PFO closure and during the subsequent follow-up (FU) at 6 and 12-months, together with lab evaluation for platelet reactivity tests (P selectin, Thromboxane B2), Prostaglandin E1 and 2 (PGE1, PGE2), serotonin, cytokines and prostaglandin PGE1 urinary metabolite run under aspirin therapy.

The research questions are as follows:

Does the presence of a large PFO have any impact on migraine with aura?

Do migraineurs with aura and PFO have higher biomarkers of platelet activation than control patients? and are they at higher risk of stroke and TIA recurrences based on high on clopidogrel platelet reactivity?

What is the effect of PFO severity on monthly migraine frequency and aura frequency?

What is the result of PFO closure in migraineur patients with PFO? Do Migraine with aura patients with large PFO have higher platelet activation and better migraine resolution after PFO closure?

Enrollment: 90 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patients older than 18 years with more than 2 criteria:
• Previous Stroke or TIA (transient ischemic attack)
• positive MRI for ischemic events -
• PFO with a baseline R-L shunt > 10 microembolic signals (MES) and > 20 MES during/after Valsalva Manoeuver
• Atrial septal aneurysm (ASA) or residual Chiari network or Eustachian Valve
• positive Thrombophilic screening (MTHFR/prot C/Prot S)
• Ability to sign the informed consent for the study participation

Exclusion criteria

• Patients older than 70 years
• Paroxysmal Atrial fibrillation
• Carotid, vertebral or basilar artery stenosis> 50% on duplex imaging
• Inadequate temporal bone windows (signals) for transcranial Doppler insonation
• medication overuse headache
• history of cognitive dysfunction, epilepsy, brain injury
• use of continuous positive airway pressure (CPAP) within 6 months of study enrollment
• Left Ventricular Ejection Fraction (LVEF) < 30%
• Moderate/severe mitral valve regurgitation
• Known Allergy to aspirin
• Known allergy to nickel
• Severe chronic kidney disease (GFR < 30 ml/min)
• Beck depression inventory score > or= 29
• State-trait anxiety inventory score exceeding cut-off for are and sex

Keywords: PFO, migraine, migraine with aura, aura, platelets

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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90 participants in 2 patient groups

Migraine evaluation in PFO patients

Experimental group

Description:

Patients symptomatic for migraine with/o aura and addressed to patent foramen ovale closure (Occlutech Figulla Flex II PFO occluder device) for a previous ischemic event, will receive dual antiplatelet therapy (DAPT) for 2 months after procedure and aspirin alone subsequently. Patients will undergo evaluation of platelet reactivity, serotonin and cytokines before PFO closure with a dedicated device and at 6 months follow-up and these results compared to those of a control, group of healthy subjects treated with aspirin alone

Treatment:

Device: patent foramen ovale closure

healthy subjects on aspirin treatment

No Intervention group

Description:

12 healthy subjects on 100 mg aspirin daily will be compared to PFO patients in terms of platelet reactivity, serotonin and cytokines