Cystic Fibrosis Clinical Trial
— ENDOTH-MUCOOfficial title:
Portal Hypertension and Systemic Endothelial Function: Investigation of Systemic Endothelial Dysfunction in Case of Portal Hypertension Associated With Cystic Fibrosis.
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.
Status | Recruiting |
Enrollment | 60 |
Est. completion date | December 2021 |
Est. primary completion date | December 2021 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | All |
Age group | 18 Years and older |
Eligibility |
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 ß-human chorionic gonadotropin (ß-HCG) urine test is negative; - Patient unable to provide written consent. Patient under guardianship. |
Country | Name | City | State |
---|---|---|---|
France | Hopital Foch | Suresnes |
Lead Sponsor | Collaborator |
---|---|
Hopital Foch |
France,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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 | 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). |
30 minutes | |
Secondary | 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. |
30 minutes | |
Secondary | 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. |
30 minutes | |
Secondary | 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. |
30 minutes |
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