Back to resultsPortal Hypertension and Systemic Endothelial Function (ENDOTH-MUCO)
Primary Purpose
Cystic Fibrosis, Portal Hypertension
Status
Unknown status
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
measure of endothelial function
Blood sample
Hepatic elastography
Injected abdominal CT
Sponsored by
About this trial
This is an interventional prevention trial for Cystic Fibrosis
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.
Sites / Locations
- Hopital FochRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
Cystic fibrosis with portal hypertension
Muco without portal hypertension
Portal hypertension without muco
Healthy volunteers
Arm Description
Mucoviscidosis with portal hypertension. Blood sample (21ml). Hepatic elastography (Fibroscan®). Measure of endothelial function (Endopat®). Injected abdominal CT scan.
Mucoviscidosis without portal hypertension. Blood sample (21ml). Hepatic elastography (Fibroscan®). Measure of endothelial function (Endopat®). Injected abdominal CT scan.
Portal hypertension without Mucoviscidosis. Blood sample (21ml) . Hepatic elastography (Fibroscan®). Measure of endothelial function (Endopat®). Injected abdominal CT scan.
Healthy volunteers. Blood sample (21ml) . Hepatic elastography (Fibroscan®). Measure of endothelial function (Endopat®).
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Serum levels of markers of endothelial dysfunction (tPA, thrombomodulin, Willebrandt factor, PAI1)
Blood sample (21 ml) is collected from each patients to dose the markers of endothelial dysfunction (tPA, thrombomodulin, Willebrandt factor, PAI1).
The objective is to compare for the 4 groups the relations between:
the serum levels of markers of endothelial dysfunction and peripheral endothelial function;
And the serum levels of markers of endothelial dysfunction and the presence of portal hypertension (HTP).
Endogline/Syndecan-4 ratio measurement
Blood sample (21 ml) is collected from each patients to measure the blood levels of endoglin and syndecan.
Endoglin and syndecan-4 are transmembrane glycoproteins present on endothelial cells.
The objective is to compare for the 4 group the relation between :
endoglin/syndecan-4 ratio and peripheral endothelial function;
and, endoglin/syndecan-4 ratio and presence of HTP.
Measurement of hepatic elasticity by Fibroscan®
The objective is to compare for the 4 groups the relations between hepatic elasticity and endothelial systemic function.
The Fibroscan measures the velocity of the sound wave passing through the liver from the device and then converts that measurement into a liver elasticity measurement. The result reveals the health of the liver: more the liver is hard, more his state is pathologic.
Hepatic abnormalities observed on injected abdominal CT.
All hepatic abnormalities observed on injected abdominal CT for groups A, B and C are analyzed.
The objective is to compare the hepatic radiologic abnormalities associated with HTP in cystic fibrosis with hepatic radiologic abnormalities associated with HTP from other causes.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02850692
Brief Title
Portal Hypertension and Systemic Endothelial Function
Acronym
ENDOTH-MUCO
Official Title
Portal Hypertension and Systemic Endothelial Function: Investigation of Systemic Endothelial Dysfunction in Case of Portal Hypertension Associated With Cystic Fibrosis.
Study Type
Interventional
2. Study Status
Record Verification Date
May 2020
Overall Recruitment Status
Unknown status
Study Start Date
April 18, 2016 (Actual)
Primary Completion Date
December 2021 (Anticipated)
Study Completion Date
December 2021 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hopital Foch
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cystic Fibrosis, Portal Hypertension
7. Study Design
Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
60 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Cystic fibrosis with portal hypertension
Arm Type
Experimental
Arm Description
Mucoviscidosis with portal hypertension. Blood sample (21ml). Hepatic elastography (Fibroscan®). Measure of endothelial function (Endopat®). Injected abdominal CT scan.
Arm Title
Muco without portal hypertension
Arm Type
Experimental
Arm Description
Mucoviscidosis without portal hypertension. Blood sample (21ml). Hepatic elastography (Fibroscan®). Measure of endothelial function (Endopat®). Injected abdominal CT scan.
Arm Title
Portal hypertension without muco
Arm Type
Experimental
Arm Description
Portal hypertension without Mucoviscidosis. Blood sample (21ml) . Hepatic elastography (Fibroscan®). Measure of endothelial function (Endopat®). Injected abdominal CT scan.
Arm Title
Healthy volunteers
Arm Type
Experimental
Arm Description
Healthy volunteers. Blood sample (21ml) . Hepatic elastography (Fibroscan®). Measure of endothelial function (Endopat®).
Intervention Type
Other
Intervention Name(s)
measure of endothelial function
Intervention Description
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
Biological
Intervention Name(s)
Blood sample
Intervention Description
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
Other
Intervention Name(s)
Hepatic elastography
Intervention Description
Hepatic elastography by Fibrocan®. Patient should neither eat nor drink at least 2 hours before exam. 10 successive measurements are made.
Intervention Type
Diagnostic Test
Intervention Name(s)
Injected abdominal CT
Intervention Description
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.
Primary Outcome Measure Information:
Title
Endothelial systemic function measured by EndoPAT®
Description
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.
Time Frame
30 minutes
Secondary Outcome Measure Information:
Title
Serum levels of markers of endothelial dysfunction (tPA, thrombomodulin, Willebrandt factor, PAI1)
Description
Blood sample (21 ml) is collected from each patients to dose the markers of endothelial dysfunction (tPA, thrombomodulin, Willebrandt factor, PAI1).
The objective is to compare for the 4 groups the relations between:
the serum levels of markers of endothelial dysfunction and peripheral endothelial function;
And the serum levels of markers of endothelial dysfunction and the presence of portal hypertension (HTP).
Time Frame
30 minutes
Title
Endogline/Syndecan-4 ratio measurement
Description
Blood sample (21 ml) is collected from each patients to measure the blood levels of endoglin and syndecan.
Endoglin and syndecan-4 are transmembrane glycoproteins present on endothelial cells.
The objective is to compare for the 4 group the relation between :
endoglin/syndecan-4 ratio and peripheral endothelial function;
and, endoglin/syndecan-4 ratio and presence of HTP.
Time Frame
30 minutes
Title
Measurement of hepatic elasticity by Fibroscan®
Description
The objective is to compare for the 4 groups the relations between hepatic elasticity and endothelial systemic function.
The Fibroscan measures the velocity of the sound wave passing through the liver from the device and then converts that measurement into a liver elasticity measurement. The result reveals the health of the liver: more the liver is hard, more his state is pathologic.
Time Frame
30 minutes
Title
Hepatic abnormalities observed on injected abdominal CT.
Description
All hepatic abnormalities observed on injected abdominal CT for groups A, B and C are analyzed.
The objective is to compare the hepatic radiologic abnormalities associated with HTP in cystic fibrosis with hepatic radiologic abnormalities associated with HTP from other causes.
Time Frame
30 minutes
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Dominique Grenet, MD
Phone
33(0)146252582
Email
d.grenet@hopital-foch.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dominique Grenet, MD
Organizational Affiliation
Hopitral Foch
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hopital Foch
City
Suresnes
ZIP/Postal Code
92150
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dominique Grenet, MD
Phone
33(0)146252582
Email
d.grenet@hopital-foch.org
12. IPD Sharing Statement
Plan to Share IPD
No
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Portal Hypertension and Systemic Endothelial Function
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