pLatelEts And MigRaine iN patEnt foRamen Ovale - Clinical Trial for Platelet Aggregation, Spontaneous | NCT03521193

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Primary Purpose

Status

Completed

Phase

Not Applicable

Locations

Italy

Study Type

Interventional

Intervention

patent foramen ovale closure

About this trial

This is an interventional treatment trial for Platelet Aggregation, Spontaneous focused on measuring Migraine;, PFO, platelet reactivity, aura

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Centro Cardiologico Monzino, IRCCS

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Migraine evaluation in PFO patients

healthy subjects on aspirin treatment

Arm Description

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

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

Outcomes

Primary Outcome Measures

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

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

Secondary Outcome Measures

Platelet Activation

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

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 (Aspirin Reactivity Unit (ARU): Cut off: 550

Clinical Outcomes

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

Full Information

NCT ID

NCT03521193

First Posted

April 16, 2018

Last Updated

July 18, 2022

Sponsor

Centro Cardiologico Monzino

1. Study Identification

Unique Protocol Identification Number

NCT03521193

Brief Title

pLatelEts And MigRaine iN patEnt foRamen Ovale

Acronym

LEARNER

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2022

Overall Recruitment Status

Completed

Study Start Date

February 15, 2018 (Actual)

Primary Completion Date

October 31, 2020 (Actual)

Study Completion Date

October 31, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Centro Cardiologico Monzino

4. Oversight

Studies a U.S. FDA-regulated Drug Product

No

Studies a U.S. FDA-regulated Device Product

No

Data Monitoring Committee

No

5. Study Description

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?

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

Keywords

Migraine;, PFO, platelet reactivity, aura

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Model Description

Group 1: patients treated with PFO closure Group 2: Healthy subjects on Aspirin therapy

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

90 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Migraine evaluation in PFO patients

Arm Type

Experimental

Arm Description

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

Arm Title

healthy subjects on aspirin treatment

Arm Type

No Intervention

Arm Description

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

Intervention Type

Device

Intervention Name(s)

patent foramen ovale closure

Other Intervention Name(s)

Occlutech Figulla Flex II PFO device; aspirin

Intervention Description

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

Primary Outcome Measure Information:

Title

Change in Migraine Characteristics

Description

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

Time Frame

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

Title

Migraine Assessment by Anzola's Score

Description

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

Time Frame

Baseline, 6 months and 12-months after PFO closure

Secondary Outcome Measure Information:

Title

Platelet Activation

Description

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)

Time Frame

baseline and 6 months

Title

Platelet Reactivity Tests

Description

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 (Aspirin Reactivity Unit (ARU): Cut off: 550

Time Frame

baseline and 6 months

Title

Clinical Outcomes

Description

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

Time Frame

In hospital, six and 12 months follow-up

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

No

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Daniela Trabattoni, MD

Organizational Affiliation

Centro Cardiologico Monzino, IRCCS

Official's Role

Principal Investigator

Facility Information:

Facility Name

Centro Cardiologico Monzino, IRCCS

City

Milan

State/Province

MI

ZIP/Postal Code

20138

Country

Italy

12. IPD Sharing Statement

Plan to Share IPD

No

Citations:

PubMed Identifier

35818509

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.

Results Reference

derived

pLatelEts And MigRaine iN patEnt foRamen Ovale (LEARNER)

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

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial