Migraine HeadacheMANETNCT06046508
Migraine With Aura and Patent Foramen Ovale: Identification of Biomarkers to Select Patients In Whom Intervention Would Be Beneficial (MANET)
An observational study of Migraine Headache and PFO - Patent Foramen Ovale, run by Centro Cardiologico Monzino at 3 sites in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Migraine Headache, PFO - Patent Foramen Ovale
- What is being tested?
- blood samples collection
- How many people
- 120 participants
- Where
- 3 sitesItaly
- Study dates
- 18 May 2023to Apr 2025
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
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.
Who may be able to join
- 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
Who cannot join
- 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)
Trial locations and contacts
3 sites in 1 country.
Italy3 sites, 2 recruiting
- Active, not recruiting
Università di Cagliari
Cagliari, 09124
- Not yet recruiting
Azienda Ospedaliera Universitaria "Federico II"
Naples, 80131
Giuseppe Gargiulo, MD, PhD, giuseppe.gargiulo1@unina.it
- Recruiting
IRCCS Policlinico San Donato
San Donato Milanese, Milan, 20097
Massimo Chessa, MD, PhD, 0252774846, Massimo.chessa@grupposandonato.it
About this study
Official title: Migraine With Aura and Causal or Incidental Patent Foramen Ovale (PFO): Identification of Biomarker(s) to Select Patients Who Would Most Benefit From PFO Closure. The MANET Study
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.
Read the detailed description
Patients with PFO, who meet all the inclusion and none of the exclusion criteria, will be enrolled in the study. Patients will undergo percutaneous correction of PFO and the following evaluations as clinical practice:
- thrombophilic screening (factor V and II and MTHFR gene mutation); sampling for homocysteine, Protein C (Prot C), Protein S (Prot S) and antithrombin III assay;
- anatomic evaluation of the SIA (Saccular intracranial aneurysm) by color-doppler TT echocardiogram and intracardiac ultrasound for definition of the anatomy of the fossa ovalis: tunneled appearance; absence of SIA aneurysm; bulging of the SIA; convex right/left SIA aneurysm;
- quantification of right-left intracardiac shunt by CT doppler;
- classification of migraine according to Anzola scale at baseline visit, post PFO correction, at follow-up at 6 and 12 months.
For the purpose of the study, blood sampling will be performed for evaluation of platelet reactivity; oxidative stress, aggregability, and deformability of red blood cells; and isolation of Endothelial Colony Forming Cells (ECFCs) for analysis of endothelial function. The latter in particular will be evaluated in comparison with the endothelial function of 30 subjects without known disease with age > 18 years, enrolled as a control group.
All analyses will be performed before PFO correction and 180 days after surgery.
- Conditions
- Migraine Headache, PFO - Patent Foramen Ovale
- Being tested
- blood samples collection
- Keywords
- platelets, prothrombotic platelets phenotype, metabolomics
- Medical subject headings
- Migraine Disorders, Foramen Ovale, Patent
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
blood samples collectionOther
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
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Other: blood samples collection |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
This will be accomplished ex vivo by using a microfluidic platform that recapitulates the specific shear stress profiles to which blood is exposed as it flows through the PFO
Measured: through study completion, an average of 2 years
Assess whether a unique endothelial dysfunction profile identifies migraineurs with incidental PFO
Functional profiling will be carried out, by measuring proliferation, migration and in vitro angiogenesis. The pro-inflammatory and pro-thrombotic phenotype of the cells will be assessed using a panel of molecular markers. Platelet adhesion will be determined on resting and activated ECFC under flow conditions; thrombin generation will be measured using a cell-based assay.
Measured: through study completition, an average of 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Sep 2023
- Study start18 May 2023
- Primary completionApr 2025 (estimated)
- Study completionApr 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Migraine HeadacheStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Centro Cardiologico Monzino
- Sponsor type
- University, hospital or other
- Collaborators
- IRCCS Policlinico S. Donato, Università di Cagliari, Federico II University
- Responsible party
- Sponsor
- Investigators
- Daniela Trabattoni, MD, Principal investigator, IRCCS Centro Cardiologico Monzino
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06046508
- Sponsor's protocol ID
- CCM 1934
- Acronym
- MANET
- Status last verified
- Sep 2023
- First submitted
- 21 Aug 2023
- Last updated
- 8 Feb 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Migraine With Aura and Causal or Incidental Patent Foramen Ovale (PFO): Identification of Biomarker(s) to Select Patients Who Would Most Benefit From PFO Closure. The MANET Study
- ClinicalTrials.gov ID
- NCT06046508
- Acronym / sponsor ID
- MANET / CCM 1934
- Conditions
- Migraine Headache, PFO - Patent Foramen Ovale
- Keywords
- platelets, prothrombotic platelets phenotype, metabolomics
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Centro Cardiologico MonzinoUniversity, hospital or other
- Collaborators
- IRCCS Policlinico S. Donato, Università di Cagliari, Federico II University
- Study start
- 18 May 2023 (actual)
- Primary completion
- Apr 2025 (estimated)
- Study completion
- Apr 2025 (estimated)
- First posted
- 21 Sep 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Patients with PFO, who meet all the inclusion and none of the exclusion criteria, will be enrolled in the study. Patients will undergo percutaneous correction of PFO and the following evaluations as clinical practice:
- thrombophilic screening (factor V and II and MTHFR gene mutation); sampling for homocysteine, Protein C (Prot C), Protein S (Prot S) and antithrombin III assay;
- anatomic evaluation of the SIA (Saccular intracranial aneurysm) by color-doppler TT echocardiogram and intracardiac ultrasound for definition of the anatomy of the fossa ovalis: tunneled appearance; absence of SIA aneurysm; bulging of the SIA; convex right/left SIA aneurysm;
- quantification of right-left intracardiac shunt by CT doppler;
- classification of migraine according to Anzola scale at baseline visit, post PFO correction, at follow-up at 6 and 12 months.
For the purpose of the study, blood sampling will be performed for evaluation of platelet reactivity; oxidative stress, aggregability, and deformability of red blood cells; and isolation of Endothelial Colony Forming Cells (ECFCs) for analysis of endothelial function. The latter in particular will be evaluated in comparison with the endothelial function of 30 subjects without known disease with age > 18 years, enrolled as a control group.
All analyses will be performed before PFO correction and 180 days after surgery.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Sigle arm study | – | Other: blood samples collectionPatients 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 |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (6 listed)
- 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)
Key exclusion criteria (8 listed)
- paroxysmal/refractory atrial fibrillation
- TSA vasculopathy
- left ventricular ejection fraction <30%
- moderate/severe mitral valve regurgitation
- need for long-term anticoagulant therapy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| blood samples collectionpatients, 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 | Other | Sigle arm study |
Primary outcome
Number of migraineurs patients with Platelet activation
Time frame: through study completion, an average of 2 years
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.
Number of migraineurs patients with high Thrombin generation levels
Time frame: through study completion, an average of 2 years
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.
levels of the oxidative status in PFO patients
Time frame: through study completion, an average of 2 years
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.
Number of migraineurs patients with Untargeted metabolomics
Time frame: through study completion, an average of 2 years
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.
2 secondary outcomes
Elucidate whether mechanical stress related to the right-to-left shunt may influence Erythrocyte behavior affecting in turn oxidative stress status
Time frame: through study completion, an average of 2 years
Assess whether a unique endothelial dysfunction profile identifies migraineurs with incidental PFO
Time frame: through study completition, an average of 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Feb 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Daniela Trabattoni, MD principal investigator
IRCCS Centro Cardiologico Monzino
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Migraine Headache and PFO - Patent Foramen Ovale, run by Centro Cardiologico Monzino at 3 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 8 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Daniela Trabattoni, MD (0285800 ext. 2780, daniela.trabattoni@cardiologicomonzino.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of migraineurs patients with Platelet activation (time frame: through study completion, an average of 2 years). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Feb 2024.