Platelet Aggregation, SpontaneousLEARNERNCT03521193
pLatelEts And MigRaine iN patEnt foRamen Ovale
A study testing patent foramen ovale closure in people with Platelet Aggregation, Spontaneous and Migraine With Aura, run by Centro Cardiologico Monzino at 1 site in Italy.
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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Platelet Aggregation, Spontaneous, Migraine With Aura, Patent Foramen Ovale
- What is being tested?
- patent foramen ovale closure
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 1 siteItaly
- Study dates
- 15 Feb 2018to 31 Oct 2020
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 15Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Migraine in Patients Undergoing PFO (Patent Foramen Ovale) Closure: Evaluation of a Platelet-associated Pathophysiologic Linking Mechanism
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.
Read the 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?
- Being tested
- patent foramen ovale closure
- Keywords
- Migraine;, PFO, platelet reactivity, aura
- Medical subject headings
- Platelet Aggregation, Spontaneous, Migraine with Aura, Foramen Ovale, Patent, Migraine Disorders, Epilepsy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
patent foramen ovale closureDevice
Also called Occlutech Figulla Flex II PFO device; aspirin
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
| Study group | Role | What they receive |
|---|---|---|
| Migraine evaluation in PFO patients | Experimental | 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 Receives: Device: patent foramen ovale closure |
| healthy subjects on aspirin treatment | No intervention | 12 healthy subjects on 100 mg aspirin daily will be compared to PFO patients in terms of platelet reactivity, serotonin and cytokines |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: The outcome data were evaluated at 6-months and 12-months after PFO closure and compared to baseline
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
Measured: Baseline, 6 months and 12-months after PFO closure
Secondary outcomes (6)
Platelet Activation (I)
Platelet Thrombin generation potential in migraineurs and healthy subjects
Measured: baseline and 6 months after PFO closure
Platelet Activation (II)
Platelet Thrombin generation Potential in Migraneurs and Healthy subjects
Measured: Baseline and 6 months after PFO closure
Platelet Activation (III)
Platelets' endogenous thrombin generation potential in Migraneurs and Healthy subjects
Measured: baseline and six months after PFO closure
Platelet Activation (IV)
Platelets' functional activity measured as the amount of thrombin generation
Measured: Baseline and six-months after PFO closure
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.
Measured: baseline and 6 months after PFO Closure
Clinical Outcomes
Absence of TIA and stroke recurrences after PFO closure and during the follow-up
Measured: In hospital, six and 12 months follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 May 2018
- Study start15 Feb 2018
- Primary completion31 Oct 2020
- Study completion31 Oct 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Platelet Aggregation, SpontaneousStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Group 1: patients treated with PFO closure Group 2: Healthy subjects on Aspirin therapy
- Masking
- None (open label)
- Enrolment
- 90 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centro Cardiologico Monzino
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Daniela Trabattoni, Centro Cardiologico Monzino
- Investigators
- Daniela Trabattoni, MD, Principal investigator, Centro Cardiologico Monzino, IRCCS
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03521193
- Sponsor's protocol ID
- CCM769
- Acronym
- LEARNER
- Status last verified
- Dec 2023
- First submitted
- 16 Apr 2018
- Last updated
- 19 Apr 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 35818509
Study at a glance
From the registry record, last updated by the sponsor on 19 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Migraine in Patients Undergoing PFO (Patent Foramen Ovale) Closure: Evaluation of a Platelet-associated Pathophysiologic Linking Mechanism
- ClinicalTrials.gov ID
- NCT03521193
- Acronym / sponsor ID
- LEARNER / CCM769
- Keywords
- Migraine;, PFO, platelet reactivity, aura
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 90 participants (actual)
- Lead sponsor
- Centro Cardiologico MonzinoUniversity, hospital or other
- Study start
- 15 Feb 2018 (actual)
- Primary completion
- 31 Oct 2020 (actual)
- Study completion
- 31 Oct 2020 (actual)
- First posted
- 11 May 2018 (actual)
- Results
- Posted 19 Oct 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Group 1: patients treated with PFO closure Group 2: Healthy subjects on Aspirin therapy
| Arm | Type | Receives |
|---|---|---|
| Migraine evaluation in PFO patients | Experimental | Device: patent foramen ovale closurePatients 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 |
| healthy subjects on aspirin treatment | No intervention | –12 healthy subjects on 100 mg aspirin daily will be compared to PFO patients in terms of platelet reactivity, serotonin and cytokines |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| patent foramen ovale closureAlso: Occlutech Figulla Flex II PFO device; aspirinPts 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 | Device | Migraine evaluation in PFO patients |
Primary outcome
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
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
6 secondary outcomes
Platelet Activation (I)
Time frame: baseline and 6 months after PFO closure
Platelet Activation (II)
Time frame: Baseline and 6 months after PFO closure
Platelet Activation (III)
Time frame: baseline and six months after PFO closure
Platelet Activation (IV)
Time frame: Baseline and six-months after PFO closure
Platelet Aggregation (I)
Time frame: baseline and 6 months after PFO Closure
Clinical Outcomes
Time frame: In hospital, six and 12 months follow-up
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Apr 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35818509Trabattoni 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Daniela Trabattoni, MD principal investigator
Centro Cardiologico Monzino, IRCCS
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing patent foramen ovale closure in people with Platelet Aggregation, Spontaneous and Migraine With Aura, run by Centro Cardiologico Monzino at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Oct 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03521193, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Apr 2024.