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Completed

NCT Number: NCT03521193

pLatelEts And MigRaine iN patEnt foRamen Ovale

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.

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Key information

Conditions

Platelet Aggregation, Spontaneous Brain Diseases Cardiovascular Abnormalities Cardiovascular Diseases Central Nervous System Diseases Congenital Abnormalities Congenital, Hereditary, and Neonatal Diseases and Abnormalities Epilepsy Foramen Ovale, Patent Headache Disorders Headache Disorders, Primary Heart Defects, Congenital Heart Diseases Heart Septal Defects Heart Septal Defects, Atrial Migraine Disorders Migraine With Aura Nervous System Diseases Patent Foramen Ovale

Age range

18 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Centro Cardiologico Monzino, IRCCS

Milan, MI, 20138, Italy

About this study

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?

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

patent foramen ovale closure

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

Other names: Occlutech Figulla Flex II PFO device; aspirin

Primary outcomes

  1. Change in Migraine Characteristics

    Time frame: The outcome data were evaluated at 6-months and 12-months after PFO closure and compared to baseline

    The evaluation in absolute numbers of patients fully responders, non-responders or with a moderate benefit on migraine symptoms after PFO Closure was performed

  2. Migraine Assessment by Anzola's Score

    Time frame: Baseline, 6 months and 12-months after PFO closure

    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

Secondary outcomes

  1. Platelet Activation (I)

    Time frame: baseline and 6 months after PFO closure

    Platelet Thrombin generation potential in migraineurs and healthy subjects

  2. Platelet Activation (II)

    Time frame: Baseline and 6 months after PFO closure

    Platelet Thrombin generation Potential in Migraneurs and Healthy subjects

  3. Platelet Activation (III)

    Time frame: baseline and six months after PFO closure

    Platelets' endogenous thrombin generation potential in Migraneurs and Healthy subjects

  4. Platelet Activation (IV)

    Time frame: Baseline and six-months after PFO closure

    Platelets' functional activity measured as the amount of thrombin generation

  5. Platelet Aggregation (I)

    Time frame: baseline and 6 months after PFO Closure

    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.

  6. Clinical Outcomes

    Time frame: In hospital, six and 12 months follow-up

    Absence of TIA and stroke recurrences after PFO closure and during the follow-up

Sponsors and collaborators

Lead sponsor

Centro Cardiologico Monzino

Other

Registry information

Official study title

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

Acronym: LEARNER

Important dates

Study start
2018
Primary completion
2020
Study completion
2020
First posted
May 11, 2018
Registry last updated
Apr 19, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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