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
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 120
- 试验地点
- 3
- 主要终点
- Number of migraineurs patients with Platelet activation
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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)
结局指标
主要结局
Number of migraineurs patients with Platelet activation
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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.
次要结局
- 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)