Migraine With Aura and Patent Foramen Ovale: Identification of Biomarkers to Select Patients In Whom Intervention Would Be Beneficial (MANET)

NCT06046508 | Unknown

• 1 other identifier: CCM 1934
• Study Type: observational
• Target: 120
• Locations: 1 country
• Sites: 3

Brief Summary

This is a multicenter prospective observational study aimed to asses whether a specific prothrombotic platelet phenotype can discern migraine patients with PFO (patent forame ovale) - related symptoms from patients with incidental PFO. The study will also explore additional distinguishing features of causal and incidental PFO using a metabolomics approach. It involves the enrollment of well-characterized patient cohorts and an ex vivo approach using comparative cell biology models that reproduce the most critical aspects of the clinical scenario.

Conditions

Migraine Headache; PFO - Patent Foramen Ovale

Keywords

platelets; prothrombotic platelets phenotype; metabolomics

Outcome Measures

Primary Outcomes (4)

• Number of migraineurs patients with Platelet activation

  Fresh whole blood will be stained for tissue factor (TF) expression, platelet activation markers \[P-selectin and activated glycoprotein IIbIIIa\] and annexinV binding to phosphatidylserine (PS). Flow cytometry analysis will be performed on fixed samples. Platelet procoagulant potential will be assessed by thrombin generation assay. The CAT assay (Chloramphenico Acetyltransferase) lwill be performed in the presence of a neutralizing anti-Tisse Factor (aTF) antibody (Ab) to assess the contribution of TF, and by adding an excess of exogenous phospholipids.

  through study completion, an average of 2 years

• Number of migraineurs patients with high Thrombin generation levels

  Flow cytometry MV characterization will be performed on stored patients' plasma samples. On the same plasma samples, MV procoagulant potential will be assessed by thrombin generation assay.

  through study completion, an average of 2 years

• levels of the oxidative status in PFO patients

  RBC (red blood cells) deformability and aggregability, generation of oxygen radicals in RBC and platelets of the overall enrolled population will be analyzed at T0 and at T1. Systemic redox status will be quantified by evaluating concentrations of both reduced glutathione (GSH) and its oxidized form GSSG (oxidized glutathione) on stored samples.

  through study completion, an average of 2 years

• Number of migraineurs patients with Untargeted metabolomics

  The metabolomic patterns of plasma, urine and platelets/ECFC (endothelial-colony forming cells) of the enrolled population will be investigated by a combined use of spectroscopy and multivariate and univariate statistical tools in order to identify the molecular fingerprint that could build a score able to identify patients with incidental PFO.

  through study completion, an average of 2 years

Secondary Outcomes (2)

• Elucidate whether mechanical stress related to the right-to-left shunt may influence Erythrocyte behavior affecting in turn oxidative stress status

  through study completion, an average of 2 years

• Assess whether a unique endothelial dysfunction profile identifies migraineurs with incidental PFO

  through study completition, an average of 2 years

Study Arms (1)

Sigle arm study

Patients with migraine headache with aura (MHA), patent foramen ovale (PFO) and previous neurological event (transient ischemic attack -TIA- or stroke) with clinical indication for percutaneous correction of the defect according to guidelines will be enrolled

Other: blood samples collection

Interventions

blood samples collection OTHER

patients, who meet all the inclusion criteria and none of the exclusion criteria, will be enrolled and they will perform a blood withdrawal before PFO correction and 180 days after the intervention

Sigle arm study

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with MHA, PFO and previous neurological event (TIA or stroke) with clinical indication for percutaneous correction of the defect according to guidelines. As a control group, 30 subjects without known disease with age \> 18 years will be enrolled.

You may qualify if:

• presence of PFO with right-left shunt at baseline \> 10 MES and during Valsalva \> 20 MES
• previous Stroke or TIA
• positive MRI for ischemic outcomes
• SIA aneurysm or residual Chiari/Eustachian valve network
• thrombophilic screening positivity (MTHFR/prot C/prot S)
• cability to sign informed consent for study participation and adherence to planned clinical follow-ups

You may not qualify if:

• paroxysmal/refractory atrial fibrillation
• TSA vasculopathy
• left ventricular ejection fraction \<30%
• moderate/severe mitral valve regurgitation
• need for long-term anticoagulant therapy
• allergy or intolerance to antiplatelet therapy
• nickel allergy
• severe chronic kidney disease (GFR \< 30 mL/min)

Sponsors & Collaborators

• Centro Cardiologico Monzino: lead
• IRCCS Policlinico S. Donato: collaborator
• Università di Cagliari: collaborator
• Federico II University: collaborator

Study Sites (3)

IRCCS Policlinico San Donato

San Donato Milanese, Milan, 20097, Italy

RECRUITING

Università di Cagliari

Cagliari, 09124, Italy

ACTIVE NOT RECRUITING

Azienda Ospedaliera Universitaria "Federico II"

Napoli, 80131, Italy

NOT YET RECRUITING

Biospecimen

Retention: SAMPLES WITHOUT DNA

blood samples will be used for platelet and erythrocyte function analysis and assessment of endothelial function

MeSH Terms

Conditions

Migraine Disorders; Foramen Ovale, Patent

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

Study Officials

• Daniela Trabattoni, MD

  IRCCS Centro Cardiologico Monzino

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Daniela Trabattoni, MD

CONTACT

0285800; daniela.trabattoni@cardiologicomonzino.it

Marina Camera, PhD

CONTACT

025800; marina.camera@cardiologicomonzino.it

Study Design

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

Study Record Dates

• First Submitted: August 21, 2023
• First Posted: September 21, 2023
• Study Start: May 18, 2023
• Primary Completion: April 1, 2025
• Study Completion: April 1, 2025
• Last Updated: February 8, 2024

Record last verified: 2023-09

Locations

IT (3)