Portal Hypertension and Systemic Endothelial Function

NCT ID: NCT02850692

Last Updated: 2020-05-26

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-04-18
• Study Completion Date: 2021-12-31

Brief Summary

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.

Detailed Description

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.

Conditions

Cystic Fibrosis; Portal Hypertension

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Cystic fibrosis with portal hypertension

Mucoviscidosis with portal hypertension. Blood sample (21ml). Hepatic elastography (Fibroscan®). Measure of endothelial function (Endopat®). Injected abdominal CT scan.

Group Type: EXPERIMENTAL

measure of endothelial function

Intervention Type: OTHER

Arterial tone index measured by EndoPAT®. Patient should neither eat nor drink at least 4 hours before exam and should neither smoke 3 hours before the exam.

Blood sample

Intervention Type: BIOLOGICAL

21 ml of blood to measure : hepatic workup, complete blood count (CBC), platelets, prothrombin time (PT), activated partial thromboplastin time (aPTT), C-reactive protein (CRP), lipid test, ionograms, creatinine, tissue plasminogen activator factor (tPA), plasminogen activator inhibitor-1 (PAI-1), tissue factor pathway inhibitor (TFPI), Willebrand factor, soluble thrombomodulin, blood levels of endoglin and syndecan. And level beta human chorionic gonadotropin (beta-HCG) for woman only.

Hepatic elastography

Intervention Type: OTHER

Hepatic elastography by Fibrocan®. Patient should neither eat nor drink at least 2 hours before exam. 10 successive measurements are made.

Injected abdominal CT

Intervention Type: DIAGNOSTIC_TEST

Patient should neither eat nor drink at least 4 hours before exam.

The examination is not realized if an abdominal scan or an MRI was performed in the five years prior to the day of the visit.

Muco without portal hypertension

Mucoviscidosis without portal hypertension. Blood sample (21ml). Hepatic elastography (Fibroscan®). Measure of endothelial function (Endopat®). Injected abdominal CT scan.

Group Type: EXPERIMENTAL

measure of endothelial function

Intervention Type: OTHER

Arterial tone index measured by EndoPAT®. Patient should neither eat nor drink at least 4 hours before exam and should neither smoke 3 hours before the exam.

Blood sample

Intervention Type: BIOLOGICAL

21 ml of blood to measure : hepatic workup, complete blood count (CBC), platelets, prothrombin time (PT), activated partial thromboplastin time (aPTT), C-reactive protein (CRP), lipid test, ionograms, creatinine, tissue plasminogen activator factor (tPA), plasminogen activator inhibitor-1 (PAI-1), tissue factor pathway inhibitor (TFPI), Willebrand factor, soluble thrombomodulin, blood levels of endoglin and syndecan. And level beta human chorionic gonadotropin (beta-HCG) for woman only.

Hepatic elastography

Intervention Type: OTHER

Hepatic elastography by Fibrocan®. Patient should neither eat nor drink at least 2 hours before exam. 10 successive measurements are made.

Injected abdominal CT

Intervention Type: DIAGNOSTIC_TEST

Patient should neither eat nor drink at least 4 hours before exam.

The examination is not realized if an abdominal scan or an MRI was performed in the five years prior to the day of the visit.

Portal hypertension without muco

Portal hypertension without Mucoviscidosis. Blood sample (21ml) . Hepatic elastography (Fibroscan®). Measure of endothelial function (Endopat®). Injected abdominal CT scan.

Group Type: EXPERIMENTAL

measure of endothelial function

Intervention Type: OTHER

Arterial tone index measured by EndoPAT®. Patient should neither eat nor drink at least 4 hours before exam and should neither smoke 3 hours before the exam.

Blood sample

Intervention Type: BIOLOGICAL

21 ml of blood to measure : hepatic workup, complete blood count (CBC), platelets, prothrombin time (PT), activated partial thromboplastin time (aPTT), C-reactive protein (CRP), lipid test, ionograms, creatinine, tissue plasminogen activator factor (tPA), plasminogen activator inhibitor-1 (PAI-1), tissue factor pathway inhibitor (TFPI), Willebrand factor, soluble thrombomodulin, blood levels of endoglin and syndecan. And level beta human chorionic gonadotropin (beta-HCG) for woman only.

Hepatic elastography

Intervention Type: OTHER

Hepatic elastography by Fibrocan®. Patient should neither eat nor drink at least 2 hours before exam. 10 successive measurements are made.

Injected abdominal CT

Intervention Type: DIAGNOSTIC_TEST

Patient should neither eat nor drink at least 4 hours before exam.

The examination is not realized if an abdominal scan or an MRI was performed in the five years prior to the day of the visit.

Healthy volunteers

Healthy volunteers. Blood sample (21ml) . Hepatic elastography (Fibroscan®). Measure of endothelial function (Endopat®).

Group Type: EXPERIMENTAL

measure of endothelial function

Intervention Type: OTHER

Arterial tone index measured by EndoPAT®. Patient should neither eat nor drink at least 4 hours before exam and should neither smoke 3 hours before the exam.

Blood sample

Intervention Type: BIOLOGICAL

21 ml of blood to measure : hepatic workup, complete blood count (CBC), platelets, prothrombin time (PT), activated partial thromboplastin time (aPTT), C-reactive protein (CRP), lipid test, ionograms, creatinine, tissue plasminogen activator factor (tPA), plasminogen activator inhibitor-1 (PAI-1), tissue factor pathway inhibitor (TFPI), Willebrand factor, soluble thrombomodulin, blood levels of endoglin and syndecan. And level beta human chorionic gonadotropin (beta-HCG) for woman only.

Hepatic elastography

Intervention Type: OTHER

Hepatic elastography by Fibrocan®. Patient should neither eat nor drink at least 2 hours before exam. 10 successive measurements are made.

Interventions

measure of endothelial function

Arterial tone index measured by EndoPAT®. Patient should neither eat nor drink at least 4 hours before exam and should neither smoke 3 hours before the exam.

Intervention Type: OTHER

Blood sample

21 ml of blood to measure : hepatic workup, complete blood count (CBC), platelets, prothrombin time (PT), activated partial thromboplastin time (aPTT), C-reactive protein (CRP), lipid test, ionograms, creatinine, tissue plasminogen activator factor (tPA), plasminogen activator inhibitor-1 (PAI-1), tissue factor pathway inhibitor (TFPI), Willebrand factor, soluble thrombomodulin, blood levels of endoglin and syndecan. And level beta human chorionic gonadotropin (beta-HCG) for woman only.

Intervention Type: BIOLOGICAL

Hepatic elastography

Hepatic elastography by Fibrocan®. Patient should neither eat nor drink at least 2 hours before exam. 10 successive measurements are made.

Intervention Type: OTHER

Injected abdominal CT

Patient should neither eat nor drink at least 4 hours before exam.

The examination is not realized if an abdominal scan or an MRI was performed in the five years prior to the day of the visit.

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Hopital Foch

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dominique Grenet, MD

Role: PRINCIPAL_INVESTIGATOR

Hopitral Foch

Locations

Hopital Foch

Suresnes, , France

Site Status: RECRUITING

Countries

France

Central Contacts

Dominique Grenet, MD

Role: CONTACT

d.grenet@hopital-foch.org

33(0)146252582

Facility Contacts

Dominique Grenet, MD

Role: primary

d.grenet@hopital-foch.org

33(0)146252582

Other Identifiers

2015-A01872-47

Identifier Type: OTHER

Identifier Source: secondary_id

2015/33

Identifier Type: -

Identifier Source: org_study_id