pLatelEts And MigRaine iN patEnt foRamen Ovale

NCT ID: NCT03521193

Last Updated: 2024-04-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 90 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-02-15
• Study Completion Date: 2020-10-31

Brief Summary

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.

Detailed 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?

Conditions

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Migraine evaluation in PFO patients

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

Group Type: EXPERIMENTAL

patent foramen ovale closure

Intervention Type: DEVICE

Pts undergoing PFO closure will receive 2-months of DAPT and 6 months of aspirin after patent foramen ovale (PFO) closure; they will be compared to healthy subjects on aspirin treatment

healthy subjects on aspirin treatment

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

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

patent foramen ovale closure

Pts undergoing PFO closure will receive 2-months of DAPT and 6 months of aspirin after patent foramen ovale (PFO) closure; they will be compared to healthy subjects on aspirin treatment

Intervention Type: DEVICE

Other Intervention Names

Occlutech Figulla Flex II PFO device; aspirin

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Centro Cardiologico Monzino

OTHER

Sponsor Role: lead

Responsible Party

Daniela Trabattoni

MD, FACC

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Daniela Trabattoni, MD

Role: PRINCIPAL_INVESTIGATOR

Centro Cardiologico Monzino, IRCCS

Locations

Centro Cardiologico Monzino, IRCCS

Milan, MI, Italy

Countries

Italy

References

Trabattoni D, Brambilla M, Canzano P, Becchetti A, Teruzzi G, Porro B, Fiorelli S, Muratori M, Tedesco CC, Veglia F, Montorsi P, Bartorelli AL, Tremoli E, Camera M. Migraine in Patients Undergoing PFO Closure: Characterization of a Platelet-Associated Pathophysiological Mechanism: The LEARNER Study. JACC Basic Transl Sci. 2022 Apr 13;7(6):525-540. doi: 10.1016/j.jacbts.2022.02.002. eCollection 2022 Jun.

Reference Type: DERIVED

PMID: 35818509 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

CCM769

Identifier Type: -

Identifier Source: org_study_id