Portal Hypertension and Systemic Endothelial Function: Investigation of Systemic Endothelial Dysfunction in Case of Portal Hypertension Associated With Cystic Fibrosis.
试验速览
- 阶段
- 不适用
- 发起方
- Hopital Foch
- 入组人数
- 60
- 试验地点
- 2
- 主要终点
- Endothelial systemic function measured by EndoPAT®
研究概览
简要总结
Cystic fibrosis can affect organs other than the lungs. Liver disease affects about 30% of patients: its main manifestation is the development of portal hypertension (PHT). The pathophysiology of this comorbidity is still poorly understood. It was previously considered secondary to the formation of biliary cirrhosis but another hypothesis would be that of a primitive pathology of venous vessels may cause the gradual emergence of portal hypertension without cirrhosis. Evidence indiscutly suggest that cystic fibrosis is associated with a specific endothelial dysfunction, especially as the CFTR (Cystic Fibrosis Transmembrane conductance Regulator) protein is expressed on the surface of endothelial cells. The investigators hypothesize that liver disease related to PHT-associated cystic fibrosis is associated with systemic endothelial dysfunction.
The aim is:
To demonstrate a systemic endothelial dysfunction in patients with cystic fibrosis when associated with PHT.
To study the correlations between measures of systemic endothelial function and serum markers of endothelial dysfunction and between measures of liver stiffness and systemic endothelial function.
详细描述
Prospective , monocentric study, with four groups of patients:
- Patients with cystic fibrosis and PHT
- Cystic fibrosis patients without PHT
- Patients free from cystic fibrosis with PHT from other causes
- Healthy controls. One study visit, no follow-up.
During the visit the following examinations will be performed:
- Collection of a blood sample of 21 mL.
- Liver eElastography achieved through hardware FibroScan® -
- Measurement of endothelial function with Endopat®
- Contrast-enhanced tomography. Abdominal CT scan will not be performed in healthy volunteers.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Patients over 18 years.
- •Patients affiliated to a social security scheme
- •Patients who have given their written consent
- •Four study groups:
- •Group A: Patients with cystic fibrosis (CF) with liver damage and diagnosis of CF is based on sweat test and genetic analysis). PHT diagnosis is based on tomographic criteria portal vein width superior to> 15 mm, portosystemic shunt and / or splenomegaly
- •Group B: cystic fibrosis patients without PHT diagnosis is based on sweat test and genetic analysis). Absence of PHTP is predicated on tomographic of Scanner.
- •Group C: Patients free of CF with PHT related to another cause. Patients followed for viral liver disease (hepatitis B or C) or idiopathic portal venous system disorder, with or without cirrhosis. The diagnosis of PHT is based on tomographic criteria portal vein width superior to> 15 mm, highlighting porto-systemic shunt, splenomegaly) and / or indirect signs namely ascitis or esophageal varices.
- •Group D: Healthy controls.
排除标准
- •Patients suffering from uncontrolled hypertension despite treatment (systolic BP> 160 mmHg);
- •Patient with uncontrolled diabetes (glycated Hb measurement done during the last 3 months > 7%);
- •Patients with uncorrected dyslipidemia;
- •Patient suffering from a sleep apnea syndrome;
- •Patients with severe coagulation disorders: PR< 50%, platelets < 30,000 / microL, current anticoagulant treatment;
- •Patient with contra-indication to the injection of iodinated contrast material, including history of hypersensitivity to iodinated contrast media or renal clearance failure <50 ml / min Modification of Diet in Renal Disease (MDRD) formula
- •Patients allergic to latex which contra-indicates endothelial function measurement;
- •Acute pathology unresolved at the time of inclusion: respiratory exacerbation, ongoing infection, recent thrombosis;
- •Smoking history> 10 pack-years;
- •Vasoactive therapy that may interfere with the measurement of endothelial function and cannot be stopped 24 hours before the measurement: nitrates, beta-blockers, angiotensin converting enzyme inhibitors, calcium channel blockers, inhibitors of endothelin receptors, similar prostacyclin analog, inhibitors of phosphodiesterases;
- •Pregnant and lactating women (all patients with childbearing potential will only be included if their β-human chorionic gonadotropin (β-HCG) urine test is negative;
- •Patient unable to provide written consent. Patient under guardianship.
结局指标
主要结局
Endothelial systemic function measured by EndoPAT®
时间窗: 30 minutes
To compare the systemic endothelial function between the four study groups, the arterial tone index is measured by EndoPAT®. The EndoPAT® is the leading medical device for noninvasive endothelial function assessment. It quantifies the endothelium-mediated changes in vascular tone, elicited by a 5-minute occlusion of the brachial artery (using a standard blood pressure cuff). When the cuff is released, the surge of blood flow causes an endothelium-dependent. Flow Mediated Dilatation (FMD). The dilatation, manifested as Reactive Hyperemia, is captured by EndoPAT® as an increase in the PAT Signal amplitude. A post-occlusion to pre-occlusion ratio is calculated by the EndoPAT® software, providing the arterial tone index.
次要结局
- Hepatic abnormalities observed on injected abdominal CT.(30 minutes)
- Serum levels of markers of endothelial dysfunction (tPA, thrombomodulin, Willebrandt factor, PAI1)(30 minutes)
- Measurement of hepatic elasticity by Fibroscan®(30 minutes)
- Endogline/Syndecan-4 ratio measurement(30 minutes)