pLatelEts And MigRaine iN patEnt foRamen Ovale

Migraine With Aura Clinical Trial

— LEARNER  

Official title:

Migraine in Patients Undergoing PFO (Patent Foramen Ovale) Closure: Evaluation of a Platelet-associated Pathophysiologic Linking Mechanism

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03521193
• Other study ID #: CCM769
• Status: Completed
• Phase: N/A
• Start date: February 15, 2018
• Est. completion date: October 31, 2020

Study information

• Verified date: December 2023
• Source: Centro Cardiologico Monzino
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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?

Recruitment information / eligibility

• Status: Completed
• Enrollment: 90
• Est. completion date: October 31, 2020
• Est. primary completion date: October 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Foramen Ovale, Patent
• Migraine Disorders
• Migraine with Aura
• Patent Foramen Ovale
• Platelet Aggregation, Spontaneous

Intervention

Device:
• 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

Locations

Country	Name	City	State
Italy	Centro Cardiologico Monzino, IRCCS	Milan	MI

Sponsors (1)

Lead Sponsor	Collaborator
Centro Cardiologico Monzino

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Migraine Characteristics	The evaluation in absolute numbers of patients fully responders, non-responders or with a moderate benefit on migraine symptoms after PFO Closure was performed	The outcome data were evaluated at 6-months and 12-months after PFO closure and compared to baseline
Primary	Migraine Assessment by Anzola's Score	The change in migraine severity, incidence and duration with or without aura as measured by the Anzola's score (The score is the expression of the sum of each corresponding value referring to migraine duration, frequency and the presence or absence of aura). The minimum value was 2 and the maximum 9; the higher the value, worse is the migraine classification.; Anzola's score: Duration 0=No pain 1=<6 hours 2=6-12 hours 3=>12 hours Frequency 0=No pain 1=1-4/month 2=5-9/month 3=>10/month Aura 0=No aura; 1=Aura in =1 attack	Baseline, 6 months and 12-months after PFO closure
Secondary	Platelet Activation (I)	Platelet Thrombin generation potential in migraineurs and healthy subjects	baseline and 6 months after PFO closure
Secondary	Platelet Activation (II)	Platelet Thrombin generation Potential in Migraneurs and Healthy subjects	Baseline and 6 months after PFO closure
Secondary	Platelet Activation (III)	Platelets' endogenous thrombin generation potential in Migraneurs and Healthy subjects	baseline and six months after PFO closure
Secondary	Platelet Activation (IV)	Platelets' functional activity measured as the amount of thrombin generation	Baseline and six-months after PFO closure
Secondary	Platelet Aggregation (I)	Platelet aggregation was measured on PAP-8 aggregometer (BioData). Briefly, PRP aliquots (250µL) were pipetted into a siliconized glass cuvette, stirred at 1200 rpm at 37°C and stimulated with arachidonic acid (1mM), collagen (2µg/ml), ADP (5µM), TRAP-6 (5µM). Light transmission was recorded for 5 min after stimuli addition and platelet aggregation was reported as maximal percentage of light transmission. Aspirin-treated patients were considered drug responders when platelet aggregation was less than 20% after arachidonic acid (1mM) stimulation.	baseline and 6 months after PFO Closure
Secondary	Clinical Outcomes	Absence of TIA and stroke recurrences after PFO closure and during the follow-up	In hospital, six and 12 months follow-up