Multimodal Brain Function in Migraine Patients With Patent Foramen Ovale

NCT07343154 | Not Yet Recruiting

• 1 other identifier: LYEC2025-0277
• Study Type: observational
• Target: 45
• Locations: 0 countries
• Sites: N/A

Brief Summary

This investigator-initiated, single-center prospective study is designed to clarify how patent foramen ovale (PFO) relates to brain function abnormalities in patients with drug-refractory migraine with aura (MA), and whether percutaneous PFO closure is associated with measurable, longitudinal improvements in neurophysiological and neuroimaging markers as well as clinical symptoms. The study addresses two core questions: (1) Do MA patients with clinically significant right-to-left shunt due to PFO demonstrate distinct resting-state brain function patterns-captured by high-density EEG (hdEEG), resting-state functional MRI (rs-fMRI), and standardized cognitive testing-compared with MA patients without PFO? (2) In MA patients with PFO who undergo clinically indicated percutaneous PFO closure, do these multimodal brain function measures change over time after closure (pre-procedure vs 1, 6, and 12 months), and are such changes accompanied by improvement in migraine burden, quality of life, and mood/anxiety symptoms? The protocol includes two phases. In Phase 1 (cross-sectional comparison), two groups are evaluated at baseline: MA with PFO (PFO+/MA+) and MA without PFO (PFO-/MA+). Participants complete hdEEG and rs-fMRI to characterize whole-brain power spectral density and connectivity, and undergo MATRICS Consensus Cognitive Battery (MCCB) testing and validated symptom/psychological assessments (e.g., MIDAS, MSQ v2.1, PHQ-9, GAD-7, RoPE). In Phase 2 (prospective self-controlled cohort), eligible PFO+/MA+ participants who proceed to percutaneous PFO closure as part of routine clinical care are followed longitudinally with repeated multimodal assessments at pre-closure baseline and post-closure 1, 6, and 12 months. This phase evaluates within-person trajectories of resting-state brain function (hdEEG, rs-fMRI) and cognition/emotion measures, together with migraine diary-based outcomes and patient-reported quality of life/disability and mood/anxiety scales. Key eligibility focuses on adults aged 18-65 years with ICHD-3-defined migraine with aura and a history of frequent migraine (≥4 migraine days/month during screening) despite prior preventive therapy trials; the PFO group requires echocardiographic confirmation of PFO with at least moderate right-to-left shunt (e.g., during Valsalva on contrast TEE), consistent with the study's focus on clinically meaningful shunt physiology. The primary endpoints are multimodal brain function and cognition measures. In Phase 1, the main outcomes include between-group differences in MCCB composite score, rs-fMRI whole-brain functional connectivity strength, and hdEEG spectral power across frequency bands (delta/theta/alpha/beta/gamma) and theta-band connectivity quantified by whole-brain phase-lag index (PLI). In Phase 2, the primary outcome is the 12-month post-closure change in these multimodal resting-state brain function measures, reflecting dynamic neural recovery or reorganization after PFO closure. Secondary outcomes include changes in migraine clinical metrics (monthly migraine days, attack frequency and duration, and complete remission rate), migraine-specific quality of life (MSQ v2.1), disability (MIDAS), and depression/anxiety symptom scores (PHQ-9 and GAD-7) over follow-up. Safety outcomes include adverse events potentially related to the closure procedure and routine post-procedural anti-thrombotic therapy, captured throughout follow-up.

Conditions

PFO; Cognitive Functions; Migraine; Cognitive

Outcome Measures

Primary Outcomes (1)

• Change in whole-brain network connectivity strength (FCN and MCN) from baseline to 12 months

  Connectivity matrices will be constructed using a predefined brain parcellation; whole-brain connectivity strength will be summarized as a prespecified global network strength metric (and/or network-level strength within canonical systems).

  from enrollment to the end of postoperative followup at 3 years

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Participants will be recruited from the neurology headache clinic and structural heart/cardiology services at Xiangya 2nd hospital, a tertiary care teaching hospital in Changsha, China. Potential participants will be identified during routine clinical care among adults evaluated for migraine with aura and referred for echocardiographic assessment of suspected or known patent foramen ovale. Recruitment will occur in outpatient clinics and, when applicable, during inpatient admissions, with screening based on clinical diagnosis and standard-of-care imaging performed as part of usual practice.

You may qualify if:

• 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):
• Beta-blockers
• Tricyclic antidepressants
• Verapamil or flunarizine
• Sodium valproate (or divalproex sodium)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Second Xiangya Hospital of Central South University: lead

MeSH Terms

Conditions

Migraine Disorders

Condition Hierarchy (Ancestors)

Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 3 Years
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 6, 2026
• First Posted: January 15, 2026
• Study Start: February 1, 2026
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): June 30, 2029
• Last Updated: January 15, 2026

Record last verified: 2026-01