Portal Hypertension and Systemic Endothelial Function

NCT02850692 | Unknown

• 2 other identifiers: 2015/332015-A01872-47
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

Cystic Fibrosis; Portal Hypertension

Outcome Measures

Primary Outcomes (1)

• Endothelial systemic function measured by EndoPAT®

  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.

  30 minutes

Secondary Outcomes (4)

• Serum levels of markers of endothelial dysfunction (tPA, thrombomodulin, Willebrandt factor, PAI1)

  30 minutes

• Endogline/Syndecan-4 ratio measurement

  30 minutes

• Measurement of hepatic elasticity by Fibroscan®

  30 minutes

• Hepatic abnormalities observed on injected abdominal CT.

  30 minutes

Study Arms (4)

Cystic fibrosis with portal hypertension

EXPERIMENTAL

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

Other: measure of endothelial function; Biological: Blood sample; Other: Hepatic elastography; Diagnostic Test: Injected abdominal CT

Muco without portal hypertension

EXPERIMENTAL

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

Other: measure of endothelial function; Biological: Blood sample; Other: Hepatic elastography; Diagnostic Test: Injected abdominal CT

Portal hypertension without muco

EXPERIMENTAL

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

Other: measure of endothelial function; Biological: Blood sample; Other: Hepatic elastography; Diagnostic Test: Injected abdominal CT

Healthy volunteers

EXPERIMENTAL

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

Other: measure of endothelial function; Biological: Blood sample; Other: Hepatic elastography

Interventions

measure of endothelial function 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.

Cystic fibrosis with portal hypertension; Healthy volunteers; Muco without portal hypertension; Portal hypertension without muco

Blood sample 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.

Cystic fibrosis with portal hypertension; Healthy volunteers; Muco without portal hypertension; Portal hypertension without muco

Hepatic elastography OTHER

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

Cystic fibrosis with portal hypertension; Healthy volunteers; Muco without portal hypertension; Portal hypertension without muco

Injected abdominal CT 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.

Cystic fibrosis with portal hypertension; Muco without portal hypertension; Portal hypertension without muco

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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;
• 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.

Sponsors & Collaborators

• Hopital Foch: lead

Study Sites (1)

Hopital Foch

Suresnes, 92150, France

RECRUITING

MeSH Terms

Conditions

Cystic Fibrosis; Hypertension, Portal

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Dominique Grenet, MD

  Hopitral Foch

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Dominique Grenet, MD

CONTACT

33(0)146252582; d.grenet@hopital-foch.org

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 16, 2016
• First Posted: August 1, 2016
• Study Start: April 18, 2016
• Primary Completion: December 1, 2021
• Study Completion: December 1, 2021
• Last Updated: May 26, 2020

Record last verified: 2020-05

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)