pLatelEts And MigRaine iN patEnt foRamen Ovale

NCT03521193 | Completed Results

• 1 other identifier: CCM769
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

Migraine;; PFO; platelet reactivity; aura

Outcome Measures

Primary Outcomes (2)

• 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

  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

  Baseline, 6 months and 12-months after PFO closure

Secondary Outcomes (6)

• Platelet Activation (I)

  baseline and 6 months after PFO closure

• Platelet Activation (II)

  Baseline and 6 months after PFO closure

• Platelet Activation (III)

  baseline and six months after PFO closure

• Platelet Activation (IV)

  Baseline and six-months after PFO closure

• Platelet Aggregation (I)

  baseline and 6 months after PFO Closure

Study Arms (2)

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

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

Interventions

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

Also known as: Occlutech Figulla Flex II PFO device; aspirin

Migraine evaluation in PFO patients

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Centro Cardiologico Monzino: lead

Study Sites (1)

Centro Cardiologico Monzino, IRCCS

Milan, MI, 20138, Italy

Location

Related Publications (1)

• 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.

  PMID: 35818509 DERIVED

MeSH Terms

Conditions

Platelet Aggregation, Spontaneous; Migraine with Aura; Foramen Ovale, Patent; Migraine Disorders; Epilepsy

Condition Hierarchy (Ancestors)

Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Heart Septal Defects, Atrial; Heart Septal Defects; Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Limitations and Caveats

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

Results Point of Contact

• Title: Clinical Trials' Office Chief
• Organization: Centro Cardiologico Monzino, IRCCS

alessandra.terragni@ccfm.it

+390258002

Study Officials

• Daniela Trabattoni, MD

  Centro Cardiologico Monzino, IRCCS

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, FACC

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

Study Record Dates

• First Submitted: April 16, 2018
• First Posted: May 11, 2018
• Study Start: February 15, 2018
• Primary Completion: October 31, 2020
• Study Completion: October 31, 2020
• Last Updated: April 19, 2024
• Results First Posted: October 19, 2021

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)