Clinical trial NCT03521193: pLatelEts And MigRaine iN patEnt foRamen Ovale
Official title: Migraine in Patients Undergoing PFO (Patent Foramen Ovale) Closure: Evaluation of a Platelet-associated Pathophysiologic Linking Mechanism
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Platelet Aggregation, Spontaneous
Migraine With Aura
Patent Foramen Ovale
Keywords: Migraine;
PFO
platelet reactivity
aura
Lead sponsor: Centro Cardiologico Monzino
Sponsor class: OTHER
First posted: 2018-05-11
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Group 1: patients treated with PFO closure Group 2: Healthy subjects on Aspirin therapy
Primary purpose: TREATMENT

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?

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

Primary outcomes:
measure: Change in Migraine Characteristics
timeFrame: The outcome data were evaluated at 6-months and 12-months after PFO closure and compared to baseline
measure: Migraine Assessment by Anzola's Score
timeFrame: Baseline, 6 months and 12-months after PFO closure
Secondary outcomes:
measure: Platelet Activation (I)
timeFrame: baseline and 6 months after PFO closure
measure: Platelet Activation (II)
timeFrame: Baseline and 6 months after PFO closure
measure: Platelet Activation (III)
timeFrame: baseline and six months after PFO closure
measure: Platelet Activation (IV)
timeFrame: Baseline and six-months after PFO closure
measure: Platelet Aggregation (I)
timeFrame: baseline and 6 months after PFO Closure
measure: Clinical Outcomes
timeFrame: In hospital, six and 12 months follow-up
Other outcomes:
Locations:
city: Milan
country: Italy
facility: Centro Cardiologico Monzino, IRCCS
state: MI
Study officials:
affiliation: Centro Cardiologico Monzino, IRCCS
name: Daniela Trabattoni, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.