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Migraine Relief After Patent Foramen Ovale Closure: a Single Center Analysis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03521193
Recruitment Status : Recruiting
First Posted : May 11, 2018
Last Update Posted : May 11, 2018
Information provided by (Responsible Party):
Daniela Trabattoni, Centro Cardiologico Monzino

Tracking Information
First Submitted Date  ICMJE April 16, 2018
First Posted Date  ICMJE May 11, 2018
Last Update Posted Date May 11, 2018
Actual Study Start Date  ICMJE February 15, 2018
Estimated Primary Completion Date December 30, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 9, 2018)
Migraine and aura [ Time Frame: Baseline and 6 months ]
The change in migraine severity, incidence and duration with or without aura as measured by the Anzola's score 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
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: May 9, 2018)
  • Platelet activation [ Time Frame: baseline and 6 months ]
    Platelet poor plasma levels of P selectin and serum concentration of B2-thromboxane (TXB2). (Plasma levels of P-selectin: ng/ml; Serum TXB2: ng/ml)
  • Platelet reactivity tests [ Time Frame: baseline and 6 months ]
    Verify-now Platelet Reactivity Unit (PRU): measures the P2Y12 platelet receptor blockade and platelet response to aspirin by an arachidonic acid initiated reaction. Verify-Now P2Y12 (PRU): Cut off: 208; -Verify-Now Aspirin (Apirin Reactivity Unit (ARU): Cut off: 550
  • 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Migraine Relief After Patent Foramen Ovale Closure: a Single Center Analysis
Official Title  ICMJE Migraine Characteristics in Patients Undergoing PFO (Patent Foramen Ovale) Closure: Evaluation of a Specific Risk Profile
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?

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Platelet Aggregation, Spontaneous
  • Migraine With Aura
  • Patent Foramen Ovale
Intervention  ICMJE Device: patent foramen ovale closure
Pts will receive 2-months of DAPT and 6 months of aspirin after patent foramen ovale (PFO) closure
Other Name: Occlutech Figulla Flex II PFO device; aspirin
Study Arms  ICMJE Experimental: 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
Intervention: Device: patent foramen ovale closure
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 9, 2018)
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 30, 2020
Estimated Primary Completion Date December 30, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patients older than 18 years with more than 2 criteria:
  • Previous Stroke or TIA
  • 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

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Alessandra Terragni +390258002675
Listed Location Countries  ICMJE Italy
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT03521193
Other Study ID Numbers  ICMJE CCM769
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Daniela Trabattoni, Centro Cardiologico Monzino
Study Sponsor  ICMJE Centro Cardiologico Monzino
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Daniela Trabattoni, MD Centro Cardiologico Monzino, IRCCS
PRS Account Centro Cardiologico Monzino
Verification Date May 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP