Ignite Creation Date:
2025-12-25 @ 1:08 AM
Ignite Modification Date:
2026-01-02 @ 8:23 PM
Study NCT ID:
NCT03521193
Status:
COMPLETED
Last Update Posted:
2024-04-19
First Post:
2018-04-16
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
pLatelEts And MigRaine iN patEnt foRamen Ovale
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'C566800', 'term': 'Platelet Aggregation, Spontaneous'}, {'id': 'D020325', 'term': 'Migraine with Aura'}, {'id': 'D054092', 'term': 'Foramen Ovale, Patent'}, {'id': 'D008881', 'term': 'Migraine Disorders'}, {'id': 'D004827', 'term': 'Epilepsy'}], 'ancestors': [{'id': 'D051270', 'term': 'Headache Disorders, Primary'}, {'id': 'D020773', 'term': 'Headache Disorders'}, {'id': 'D001927', 'term': 'Brain Diseases'}, {'id': 'D002493', 'term': 'Central Nervous System Diseases'}, {'id': 'D009422', 'term': 'Nervous System Diseases'}, {'id': 'D006344', 'term': 'Heart Septal Defects, Atrial'}, {'id': 'D006343', 'term': 'Heart Septal Defects'}, {'id': 'D006330', 'term': 'Heart Defects, Congenital'}, {'id': 'D018376', 'term': 'Cardiovascular Abnormalities'}, {'id': 'D002318', 'term': 'Cardiovascular Diseases'}, {'id': 'D006331', 'term': 'Heart Diseases'}, {'id': 'D000013', 'term': 'Congenital Abnormalities'}, {'id': 'D009358', 'term': 'Congenital, Hereditary, and Neonatal Diseases and Abnormalities'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'alessandra.terragni@ccfm.it', 'phone': '+390258002', 'title': "Clinical Trials' Office Chief", 'phoneExt': '675', 'organization': 'Centro Cardiologico Monzino, IRCCS'}, 'certainAgreement': {'piSponsorEmployee': True}, 'limitationsAndCaveats': {'description': 'MHA may have a multifactorial etiology. The role of oxidative stress appears consistent and corroborated by the in vitro data. The effect of serotonin and oxidative stress was tested on platelets from healthy subjects and not from pts because the Sars-Cov-2 pandemic imposed restrictions on pts enrolment. Finally, the thrombin generation capacity of platelets and MVs were included after the study started to support the pro-coagulant phenotype evidenced by ad interim flow cytometry data analysis'}}, 'adverseEventsModule': {'timeFrame': 'in -hospital, 6 months and 1 year', 'description': 'Adverse event definitions were the same adopted by clinicaltrials.gov ; EVENTS WERE COLLECTED during clinical visit in-hospital and at follow-up', 'eventGroups': [{'id': 'EG000', 'title': 'Migraine Evaluation in PFO Patients', '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. Clinical evaluation performed during in-hospital stay, at 6- and 12-months follow-up', 'otherNumAtRisk': 62, 'deathsNumAtRisk': 62, 'otherNumAffected': 0, 'seriousNumAtRisk': 62, 'deathsNumAffected': 0, 'seriousNumAffected': 0}, {'id': 'EG001', 'title': 'Healthy Subjects', 'description': 'control Healthy subjects group', 'otherNumAtRisk': 12, 'deathsNumAtRisk': 12, 'otherNumAffected': 0, 'seriousNumAtRisk': 12, 'deathsNumAffected': 0, 'seriousNumAffected': 0}], 'frequencyThreshold': '0'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Change in Migraine Characteristics', 'denoms': [{'units': 'Participants', 'counts': [{'value': '62', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Migraine Assessment After PFO Closure', 'description': 'Migraine symptoms evaluation after PFO closure'}], 'classes': [{'title': 'Migraine : Complete Migraine Resolution', 'categories': [{'measurements': [{'value': '43', 'groupId': 'OG000'}]}]}, {'title': 'Migraine : Non-responders', 'categories': [{'measurements': [{'value': '2', 'groupId': 'OG000'}]}]}, {'title': 'Migraine Symptoms improvement', 'categories': [{'measurements': [{'value': '17', 'groupId': 'OG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'The outcome data were evaluated at 6-months and 12-months after PFO closure and compared to baseline', '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', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': 'Analysis performed only in PFO Group patients as not applicable to the control Healthy subjects group'}, {'type': 'PRIMARY', 'title': "Migraine Assessment by Anzola's Score", 'denoms': [{'units': 'Participants', 'counts': [{'value': '62', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'PFO Patients Enrolled', 'description': 'We enrolled consecutive patients who met the inclusion criteria, symptomatic for migraine alone and Migraine with aura (MHA) patients. Eight patients refused to continue the study and eight were non-compliant to antiplatelet therapy during the follow-up. .\n\nThe leading indication to PFO closure was a previous TIA or stroke in 37 patients while an off-label indication was offered to 25 patients. These pts underwent PFO closure with the Occlutech Figulla device and treated with dual antiplatelet therapy (Aspirin 100 mg/day + Clopidogrel 75 mg/day), followed by aspirin 100 mg/day alone.'}], 'classes': [{'title': "Anzola's score @Baseline", 'categories': [{'measurements': [{'value': '7.2', 'spread': '1.68', 'groupId': 'OG000'}]}]}, {'title': "Anzola's score@6-mos post PFO Closure", 'categories': [{'measurements': [{'value': '1.09', 'spread': '1.47', 'groupId': 'OG000'}]}]}, {'title': "Anzola's score @12-mos post PFO closure", 'categories': [{'measurements': [{'value': '1.1', 'spread': '1.57', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Baseline, 6 months and 12-months after PFO closure', '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.\n\nAnzola'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\n\n1=Aura in ≥1 attack", 'unitOfMeasure': 'score on a scale', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'Analysis performed only in PFO Group patients as not applicable to the control Healthy subjects group'}, {'type': 'SECONDARY', 'title': 'Platelet Activation (I)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '62', 'groupId': 'OG000'}, {'value': '15', 'groupId': 'OG001'}, {'value': '62', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'PFO Patients', 'description': 'Evaluation of Platelet thrombin generation potential in PFO patients at T0'}, {'id': 'OG001', 'title': 'Healthy Subjects', 'description': 'Evaluation of Platelet thrombin generation potential in HS'}, {'id': 'OG002', 'title': 'PFO Patients at T1 (6 Mos)', 'description': 'Evaluation of Platelet thrombin generation potential in PFO patients at T1 (6 mos)'}], 'classes': [{'title': 'Lag Time', 'categories': [{'measurements': [{'value': '26.9', 'spread': '8.9', 'groupId': 'OG000'}, {'value': '30.6', 'spread': '7.2', 'groupId': 'OG001'}, {'value': '32.2', 'spread': '12.4', 'groupId': 'OG002'}]}]}, {'title': 'Time to peak', 'categories': [{'measurements': [{'value': '32.1', 'spread': '9.5', 'groupId': 'OG000'}, {'value': '37.6', 'spread': '10.2', 'groupId': 'OG001'}, {'value': '37.8', 'spread': '13', 'groupId': 'OG002'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'baseline and 6 months after PFO closure', 'description': 'Platelet Thrombin generation potential in migraineurs and healthy subjects', 'unitOfMeasure': 'min', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Platelet Activation (II)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '62', 'groupId': 'OG000'}, {'value': '12', 'groupId': 'OG001'}, {'value': '62', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'PFO Patients', 'description': 'Platelets kinetic rate (velocity index) at baseline, before PFO closure'}, {'id': 'OG001', 'title': 'Healthy Subjects', 'description': 'Platelets kinetic rate (velocity index) in healthy subjects'}, {'id': 'OG002', 'title': 'PFO Patients at T1 (6 Mos)', 'description': 'Platelets kinetic rate (velocity index) at T1, six months after PFO closure'}], 'classes': [{'categories': [{'measurements': [{'value': '29.1', 'spread': '29', 'groupId': 'OG000'}, {'value': '12.3', 'spread': '10.9', 'groupId': 'OG001'}, {'value': '17.9', 'spread': '19.9', 'groupId': 'OG002'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Baseline and 6 months after PFO closure', 'description': 'Platelet Thrombin generation Potential in Migraneurs and Healthy subjects', 'unitOfMeasure': 'nMol/L/min', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': "Analysis of platelets' intrinsic characteristics including thrombin-formation capacity, the amount of thrombin and the kinetic rate (peak velocity)"}, {'type': 'SECONDARY', 'title': 'Platelet Activation (III)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '62', 'groupId': 'OG000'}, {'value': '12', 'groupId': 'OG001'}, {'value': '62', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'PFO Patients at Baseline T0', 'description': "Evaluation of Platelets' ETP (Endogenous Thrombin Potential) capacity before PFO closure"}, {'id': 'OG001', 'title': 'Healthy Subjects', 'description': "Evaluation of Platelets' ETP (Endogenous Thrombin Potential) capacity in HS on aspirin treatment"}, {'id': 'OG002', 'title': 'PFO Patients at T1 (6 Mos)', 'description': "Evaluation of Platelets' ETP (Endogenous Thrombin Potential) capacity six months after PFO closure"}], 'classes': [{'categories': [{'measurements': [{'value': '1038', 'spread': '352', 'groupId': 'OG000'}, {'value': '781', 'spread': '319', 'groupId': 'OG001'}, {'value': '797', 'spread': '373', 'groupId': 'OG002'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'baseline and six months after PFO closure', 'description': "Platelets' endogenous thrombin generation potential in Migraneurs and Healthy subjects", 'unitOfMeasure': 'nmol/L x min', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Platelet Activation (IV)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '62', 'groupId': 'OG000'}, {'value': '12', 'groupId': 'OG001'}, {'value': '62', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'PFO Patients at Baseline T0', 'description': "Platelets' functional activity expressed as the amount of thrombin generated in PFO patients"}, {'id': 'OG001', 'title': 'Healthy Subjects', 'description': "Platelets' functional activity expressed as the amount of thrombin generated in HS on aspirin therapy"}, {'id': 'OG002', 'title': 'PFO Patients at T1 (6 Mos)', 'description': "Platelets' functional activity expressed as the amount of thrombin generated six months after PFO closure"}], 'classes': [{'categories': [{'measurements': [{'value': '115.2', 'spread': '81.2', 'groupId': 'OG000'}, {'value': '63.4', 'spread': '41.8', 'groupId': 'OG001'}, {'value': '77.2', 'spread': '59.2', 'groupId': 'OG002'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Baseline and six-months after PFO closure', 'description': "Platelets' functional activity measured as the amount of thrombin generation", 'unitOfMeasure': 'nmol/L', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Platelet Aggregation (I)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '62', 'groupId': 'OG000'}, {'value': '62', 'groupId': 'OG001'}, {'value': '12', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'PFO Patients at T0', 'description': 'Median value of platelet aggregation in PFO patients at T0 (baseline)'}, {'id': 'OG001', 'title': 'PFO Patients at T1', 'description': 'Median value of platelet aggregation in PFO patients at T1 (six months)'}, {'id': 'OG002', 'title': 'Healthy Subjects', 'description': 'Median value of platelet aggregation in PFO patients in HS patients'}], 'classes': [{'title': 'ADP (5µM)', 'categories': [{'measurements': [{'value': '153', 'groupId': 'OG000', 'lowerLimit': '92.5', 'upperLimit': '210'}, {'value': '157', 'groupId': 'OG001', 'lowerLimit': '92', 'upperLimit': '216'}, {'value': '187', 'groupId': 'OG002', 'lowerLimit': '116', 'upperLimit': '253'}]}]}, {'title': 'TRAP-6 (5µM)', 'categories': [{'measurements': [{'value': '8.5', 'groupId': 'OG000', 'lowerLimit': '5', 'upperLimit': '14'}, {'value': '8', 'groupId': 'OG001', 'lowerLimit': '4', 'upperLimit': '13'}, {'value': '11', 'groupId': 'OG002', 'lowerLimit': '9', 'upperLimit': '27'}]}]}, {'title': 'Collagen (2µg/ml)', 'categories': [{'measurements': [{'value': '62', 'groupId': 'OG000', 'lowerLimit': '23.7', 'upperLimit': '121.2'}, {'value': '76.5', 'groupId': 'OG001', 'lowerLimit': '30.2', 'upperLimit': '139.5'}, {'value': '104', 'groupId': 'OG002', 'lowerLimit': '73', 'upperLimit': '184'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': 'baseline and 6 months after PFO Closure', 'description': '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.', 'unitOfMeasure': 'AUC (AU x min)', 'dispersionType': 'Inter-Quartile Range', 'reportingStatus': 'POSTED', 'populationDescription': 'Patients were analysed at baseline before PFO closure, six months after procedure and compared to healthy subjects'}, {'type': 'SECONDARY', 'title': 'Clinical Outcomes', 'denoms': [{'units': 'Participants', 'counts': [{'value': '62', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'PFO Patients Enrolled', 'description': 'We enrolled 62 consecutive PFO patients suffering from migraine, addressed to PFO closure. The leading indication to PFO closure was a previous TIA or stroke in 37 patients while an off-label indication was offered to 25 patients.'}], 'classes': [{'title': 'In -hospital vascular complications', 'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000'}]}]}, {'title': 'device malpositioning/embolization', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}]}]}, {'title': 'Transient atrial fibrillation', 'categories': [{'measurements': [{'value': '5', 'groupId': 'OG000'}]}]}, {'title': 'TIA/stroke post PFO Closure', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}]}]}, {'title': 'Recurrent TIAs /stroke @6 months FU', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}]}]}, {'title': 'Recurrent TIAs /stroke @12 months FU', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'In hospital, six and 12 months follow-up', 'description': 'Absence of TIA and stroke recurrences after PFO closure and during the follow-up', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': 'Clinical evaluation of neurologic recurrences or death was performed during in-hospital stay and subsequent follow-up; Analysis performed only in PFO Group patients as not applicable to the control Healthy subjects group'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'PFO and Migraine Pts', 'description': '93 consecutive patients addressed to PFO closure and suffering from migraine with aura were prospectively screened. 78 patients were enrolled in the study (T0)'}, {'id': 'FG001', 'title': 'Healthy Subjects on Aspirin', 'description': '12 healthy subjects on ASA treatment were the control group for phase 2 study'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'comment': 'enrolled on the PFO closure hospitalization', 'groupId': 'FG000', 'numSubjects': '78'}, {'groupId': 'FG001', 'numSubjects': '12'}]}, {'type': 'COMPLETED', 'achievements': [{'comment': '8 pts refused to continue the study; 8 patients were non compliant to ASA treatment', 'groupId': 'FG000', 'numSubjects': '62'}, {'groupId': 'FG001', 'numSubjects': '12'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '16'}, {'groupId': 'FG001', 'numSubjects': '0'}]}], 'dropWithdraws': [{'type': 'Withdrawal by Subject', 'reasons': [{'groupId': 'FG000', 'numSubjects': '8'}, {'groupId': 'FG001', 'numSubjects': '0'}]}, {'type': 'non compliant to ASA treatment', 'reasons': [{'groupId': 'FG000', 'numSubjects': '8'}, {'groupId': 'FG001', 'numSubjects': '0'}]}]}], 'recruitmentDetails': 'Patients were enrolled at Centro Cardiologico Monzino, Milan, Italy between February 2018 and April 2020', 'preAssignmentDetails': 'After screening of 93 consecutive PFO patients suffering from migraine 15 were excluded due to unwillingness to sign the informed consent, absence of patent PFO at the invasive evaluation, intolerance to antiplatelet therapy. Finally, 78 pts were enrolled in the study and assigned to the PFO Arm; another arm included 12healthy subjects on Aspirin treatment'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '78', 'groupId': 'BG000'}, {'value': '12', 'groupId': 'BG001'}, {'value': '90', 'groupId': 'BG002'}]}], 'groups': [{'id': 'BG000', 'title': 'PFO Patients Enrolled', 'description': 'We enrolled consecutive patients who met the inclusion criteria, symptomatic for migraine alone and Migraine with aura (MHA) patients.\n\nThe leading indication to PFO closure was a previous TIA or stroke in 37 patients while an off-label indication was offered to 25 patients. These pts underwent PFO closure with the Occlutech Figulla device and treated with dual antiplatelet therapy (Aspirin 100 mg/day + Clopidogrel 75 mg/day), followed by aspirin 100 mg/day alone.'}, {'id': 'BG001', 'title': 'Healthy Subjects', 'description': 'Healthy subjects on aspirin treatment by at least 15 days were the comparative group for platelet aggregation markers and activation markers, platelet procoagulant, circulating serotonin and cell-associated procoagulant potential'}, {'id': 'BG002', 'title': 'Total', 'description': 'Total of all reporting groups'}], 'measures': [{'title': 'Age, Continuous', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '78', 'groupId': 'BG000'}, {'value': '12', 'groupId': 'BG001'}, {'value': '90', 'groupId': 'BG002'}]}], 'categories': [{'measurements': [{'value': '40.6', 'spread': '12', 'groupId': 'BG000'}, {'value': '41', 'spread': '10', 'groupId': 'BG001'}, {'value': '40.8', 'spread': '10', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '78', 'groupId': 'BG000'}, {'value': '12', 'groupId': 'BG001'}, {'value': '90', 'groupId': 'BG002'}]}], 'categories': [{'title': 'Female', 'measurements': [{'value': '63', 'groupId': 'BG000'}, {'value': '8', 'groupId': 'BG001'}, {'value': '71', 'groupId': 'BG002'}]}, {'title': 'Male', 'measurements': [{'value': '15', 'groupId': 'BG000'}, {'value': '4', 'groupId': 'BG001'}, {'value': '19', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'calculatePct': False, 'unitOfMeasure': 'Participants'}, {'title': 'Race (NIH/OMB)', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '78', 'groupId': 'BG000'}, {'value': '12', 'groupId': 'BG001'}, {'value': '90', 'groupId': 'BG002'}]}], 'categories': [{'title': 'American Indian or Alaska Native', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Asian', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Native Hawaiian or Other Pacific Islander', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Black or African American', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'White', 'measurements': [{'value': '78', 'groupId': 'BG000'}, {'value': '12', 'groupId': 'BG001'}, {'value': '90', 'groupId': 'BG002'}]}, {'title': 'More than one race', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Region of Enrollment', 'classes': [{'title': 'Italy', 'denoms': [{'units': 'Participants', 'counts': [{'value': '78', 'groupId': 'BG000'}, {'value': '12', 'groupId': 'BG001'}, {'value': '90', 'groupId': 'BG002'}]}], 'categories': [{'measurements': [{'value': '78', 'groupId': 'BG000'}, {'value': '12', 'groupId': 'BG001'}, {'value': '90', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Migraine', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '78', 'groupId': 'BG000'}, {'value': '12', 'groupId': 'BG001'}, {'value': '90', 'groupId': 'BG002'}]}], 'categories': [{'measurements': [{'value': '60', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '60', 'groupId': 'BG002'}]}]}], 'paramType': 'NUMBER', 'description': 'number of participants sffering from Migraine alone (MA)', 'unitOfMeasure': 'Migraine'}, {'title': 'Migraine with aura (MHA)', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '78', 'groupId': 'BG000'}, {'value': '12', 'groupId': 'BG001'}, {'value': '90', 'groupId': 'BG002'}]}], 'categories': [{'measurements': [{'value': '18', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '18', 'groupId': 'BG002'}]}]}], 'paramType': 'NUMBER', 'description': 'Number of patients suffering from Migraine with aura (MHA)', 'unitOfMeasure': 'Migraine with aura'}, {'title': 'Patients finally evaluated', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '62', 'groupId': 'BG000'}, {'value': '12', 'groupId': 'BG001'}, {'value': '74', 'groupId': 'BG002'}]}], 'categories': [{'measurements': [{'value': '62', 'groupId': 'BG000'}, {'value': '12', 'groupId': 'BG001'}, {'value': '74', 'groupId': 'BG002'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'participants', 'populationDescription': '8 patients refused to continue the study ; 8 patients were not compliant to aspirin treatment, therefore final analysis was performed on 62 patients'}], 'populationDescription': 'Final evaluation was performed on 62 patients. This group was compared to a control group (12 healthy subjects) on aspirin. Comparison was performed before PFO closure (T0) and during follow-up (T1) in terms of serotonin, platelet aggregation and activation markers and cell-associated procoagulant effect'}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2018-05-09', 'size': 937805, 'label': 'Study Protocol and Statistical Analysis Plan', 'hasIcf': False, 'hasSap': True, 'filename': 'Prot_SAP_000.pdf', 'typeAbbrev': 'Prot_SAP', 'uploadDate': '2021-07-27T06:53', 'hasProtocol': True}]}}, 'protocolSection': {'designModule': {'phases': ['NA'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NON_RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'Group 1: patients treated with PFO closure Group 2: Healthy subjects on Aspirin therapy'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 90}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2018-02-15', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2023-12', 'completionDateStruct': {'date': '2020-10-31', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2023-12-15', 'studyFirstSubmitDate': '2018-04-16', 'resultsFirstSubmitDate': '2021-07-27', 'studyFirstSubmitQcDate': '2018-05-09', 'lastUpdatePostDateStruct': {'date': '2024-04-19', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2021-09-21', 'studyFirstPostDateStruct': {'date': '2018-05-11', 'type': 'ACTUAL'}, 'resultsFirstPostDateStruct': {'date': '2021-10-19', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2020-10-31', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Change in Migraine Characteristics', 'timeFrame': 'The outcome data were evaluated at 6-months and 12-months after PFO closure and compared to baseline', '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'}, {'measure': "Migraine Assessment by Anzola's Score", 'timeFrame': 'Baseline, 6 months and 12-months after PFO closure', '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.\n\nAnzola'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\n\n1=Aura in ≥1 attack"}], 'secondaryOutcomes': [{'measure': 'Platelet Activation (I)', 'timeFrame': 'baseline and 6 months after PFO closure', 'description': 'Platelet Thrombin generation potential in migraineurs and healthy subjects'}, {'measure': 'Platelet Activation (II)', 'timeFrame': 'Baseline and 6 months after PFO closure', 'description': 'Platelet Thrombin generation Potential in Migraneurs and Healthy subjects'}, {'measure': 'Platelet Activation (III)', 'timeFrame': 'baseline and six months after PFO closure', 'description': "Platelets' endogenous thrombin generation potential in Migraneurs and Healthy subjects"}, {'measure': 'Platelet Activation (IV)', 'timeFrame': 'Baseline and six-months after PFO closure', 'description': "Platelets' functional activity measured as the amount of thrombin generation"}, {'measure': 'Platelet Aggregation (I)', 'timeFrame': 'baseline and 6 months after PFO Closure', 'description': '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.'}, {'measure': 'Clinical Outcomes', 'timeFrame': 'In hospital, six and 12 months follow-up', 'description': 'Absence of TIA and stroke recurrences after PFO closure and during the follow-up'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Migraine;', 'PFO', 'platelet reactivity', 'aura'], 'conditions': ['Platelet Aggregation, Spontaneous', 'Migraine With Aura', 'Patent Foramen Ovale']}, 'referencesModule': {'references': [{'pmid': '35818509', 'type': 'DERIVED', '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.'}]}, 'descriptionModule': {'briefSummary': '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.', 'detailedDescription': '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.\n\nThe research questions are as follows:\n\nDoes the presence of a large PFO have any impact on migraine with aura?\n\nDo 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?\n\nWhat is the effect of PFO severity on monthly migraine frequency and aura frequency?\n\nWhat 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?'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '70 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Patients older than 18 years with more than 2 criteria:\n* Previous Stroke or TIA (transient ischemic attack)\n* positive MRI for ischemic events -\n* PFO with a baseline R-L shunt \\> 10 microembolic signals (MES) and \\> 20 MES during/after Valsalva Manoeuver\n* Atrial septal aneurysm (ASA) or residual Chiari network or Eustachian Valve\n* positive Thrombophilic screening (MTHFR/prot C/Prot S)\n* Ability to sign the informed consent for the study participation\n\nExclusion Criteria:\n\n* Patients older than 70 years\n* Paroxysmal Atrial fibrillation\n* Carotid, vertebral or basilar artery stenosis\\> 50% on duplex imaging\n* Inadequate temporal bone windows (signals) for transcranial Doppler insonation\n* medication overuse headache\n* history of cognitive dysfunction, epilepsy, brain injury\n* use of continuous positive airway pressure (CPAP) within 6 months of study enrollment\n* Left Ventricular Ejection Fraction (LVEF) \\< 30%\n* Moderate/severe mitral valve regurgitation\n* Known Allergy to aspirin\n* Known allergy to nickel\n* Severe chronic kidney disease (GFR \\< 30 ml/min)\n* Beck depression inventory score \\> or= 29\n* State-trait anxiety inventory score exceeding cut-off for are and sex\n\nKeywords: PFO, migraine, migraine with aura, aura, platelets'}, 'identificationModule': {'nctId': 'NCT03521193', 'acronym': 'LEARNER', 'briefTitle': 'pLatelEts And MigRaine iN patEnt foRamen Ovale', 'organization': {'class': 'OTHER', 'fullName': 'Centro Cardiologico Monzino'}, 'officialTitle': 'Migraine in Patients Undergoing PFO (Patent Foramen Ovale) Closure: Evaluation of a Platelet-associated Pathophysiologic Linking Mechanism', 'orgStudyIdInfo': {'id': 'CCM769'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Migraine evaluation in PFO patients', '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', 'interventionNames': ['Device: patent foramen ovale closure']}, {'type': 'NO_INTERVENTION', 'label': 'healthy subjects on aspirin treatment', 'description': '12 healthy subjects on 100 mg aspirin daily will be compared to PFO patients in terms of platelet reactivity, serotonin and cytokines'}], 'interventions': [{'name': 'patent foramen ovale closure', 'type': 'DEVICE', 'otherNames': ['Occlutech Figulla Flex II PFO device; aspirin'], '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', 'armGroupLabels': ['Migraine evaluation in PFO patients']}]}, 'contactsLocationsModule': {'locations': [{'zip': '20138', 'city': 'Milan', 'state': 'MI', 'country': 'Italy', 'facility': 'Centro Cardiologico Monzino, IRCCS', 'geoPoint': {'lat': 45.46427, 'lon': 9.18951}}], 'overallOfficials': [{'name': 'Daniela Trabattoni, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Centro Cardiologico Monzino, IRCCS'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Centro Cardiologico Monzino', 'class': 'OTHER'}, 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'MD, FACC', 'investigatorFullName': 'Daniela Trabattoni', 'investigatorAffiliation': 'Centro Cardiologico Monzino'}}}}