Heart hole closure may rewire migraine brains, study hints

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: * Age ≥18 years and \<60 years at Screening/Baseline. * Diagnosis of migraine with aura established by a neurologist according to the International Classification of Headache Disorders, 3rd edition (ICHD-3) criteria. * Migraine history ≥1 year AND, during the 3-month screening/run-in period, an average of ≥4 migraine days per month; participant is willing and able to complete a headache diary, which will be reviewed by the investigator prior to enrollment. * Patent foramen ovale (PFO) identified by transthoracic echocardiography (TTE) and confirmed by contrast transesophageal echocardiography (cTEE), with at least moderate atrial-level right-to-left shunt (RLS) during Valsalva maneuver. * RLS grading by microbubbles in the left-sided cardiac chambers per frame on single-frame images: * No RLS: 0 microbubbles * Grade I (small): 1-10 microbubbles/frame * Grade II (moderate): 11-30 microbubbles/frame * Grade III (large): \>30 microbubbles/frame or near-complete opacification of the left chambers ("hazy" appearance) * Prior use of at least three different classes of migraine preventive therapies with either \<50% improvement in migraine frequency during treatment OR intolerable adverse effects. * At least two therapies must be from different categories among (a-f); the third may be one of (g-j): 1. Beta-blockers 2. Tricyclic antidepressants 3. Verapamil or flunarizine 4. Sodium valproate (or divalproex sodium) 5. Topiramate 6. Other anticonvulsants 7. Any therapy supported as effective by at least one positive randomized controlled trial 8. Nonsteroidal anti-inflammatory drugs (NSAIDs) 9. Metabolic agents (e.g., vitamin B2 or coenzyme Q10) 10. Traditional Chinese medicine * Participant has been on a stable daily dose regimen of preventive headache medication for ≥3 consecutive months prior to enrollment (to be verified during screening). * Written informed consent provided and willingness to comply with study procedures and follow-up schedule. Exclusion Criteria: * Expected life expectancy ≤1 year at Screening/Baseline. * Secondary migraine attributable to other causes. * History of transient ischemic attack (TIA), stroke, or intracranial hemorrhage. * Investigator-determined anatomical findings on TEE that are unfavorable for successful PFO occluder deployment or any contraindication to device implantation, including (but not limited to): * Inability to undergo/complete TEE * Vascular access unable to accommodate the delivery system * Requirement for transseptal puncture * Requirement for implantation of more than one occluder * Defect size estimated too large for successful closure * Potential interference between the occluder and other intracardiac structures * Anatomy preventing adequate apposition of the occluder discs to the atrial septum * Allergy to any component/material of the AMPLATZER™ PFO Occluder (e.g., nickel allergy). * Current or past diagnosis of severe psychiatric disorder (e.g., schizophrenia, bipolar disorder, major depressive disorder), or unstable psychiatric illness defined as psychiatric hospitalization, medication dose adjustment, or marked symptom fluctuation within the past 6 months. * Neurological and/or neurodegenerative disease (e.g., Alzheimer's disease, Parkinson's disease, multiple sclerosis), uncontrolled epilepsy/seizures within the past 1 year, central nervous system tumor, or history of traumatic brain injury. * History of myocardial infarction. * History of pacemaker implantation, atrial septal defect (ASD) closure, or left atrial appendage (LAA) closure. * Intracardiac right-to-left shunt due to causes other than PFO. * Contraindications to aspirin and/or clopidogrel, including significant thrombocytopenia, major trauma, acute clinically significant bleeding, or allergy to study medications. * Hepatic impairment defined as PT and/or APTT \>2× the upper limit of normal (ULN) OR total bilirubin ≥3 mg/dL. * Poorly controlled diabetes mellitus at Screening/Baseline (as judged by the investigator). * Poorly controlled atrial fibrillation at Screening/Baseline (as judged by the investigator). * Poorly controlled hypertension at Screening/Baseline, defined as blood pressure \>160/90 mmHg despite appropriate pharmacologic treatment. * Active autoimmune disease at Screening/Baseline (e.g., systemic lupus erythematosus, rheumatoid arthritis, polyarteritis nodosa, central nervous system granulomatous vasculitis). * Active infection at Screening/Baseline that cannot be fully resolved prior to enrollment. * Alcohol abuse or drug dependence at Screening/Baseline. * Ongoing anticoagulation therapy that cannot be discontinued. * Unable to accurately describe headache status and/or unable to complete/maintain a headache diary. * Currently participating in another device or drug clinical trial in which the primary endpoint has not been reached, or that may clinically confound this study's endpoints, or that prohibits co-enrollment. * Pregnant or planning pregnancy during the study period. * Planned elective surgery during the study period. * Any medical condition or circumstance that, in the investigator's opinion, poses a significant risk to participant safety, confounds study results, or interferes with study participation. * Any other medical or non-medical reason that, in the investigator's opinion, makes the participant unsuitable (e.g., inability to comply with study procedures/visits, plans to relocate during the study period).