Cystic FibrosisENDOTH-MUCONCT02850692
Portal Hypertension and Systemic Endothelial Function
A study testing measure of endothelial function, Blood sample and Hepatic elastography in people with Cystic Fibrosis and Portal Hypertension, run by Hopital Foch at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Cystic Fibrosis, Portal Hypertension
- What is being tested?
- measure of endothelial function, Blood sample and Hepatic elastography
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteFrance
- Study dates
- 18 Apr 2016to Dec 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
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- 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.
Trial locations and contacts
1 site in 1 country.
France1 site, 1 recruiting
- Recruiting
Hopital Foch
Suresnes, 92150
Dominique Grenet, MD, 33(0)146252582, d.grenet@hopital-foch.org
About this study
Official 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:
Read more
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.
Read the 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
- Being tested
- measure of endothelial function, Blood sample, Hepatic elastography, Injected abdominal CT
- Medical subject headings
- Cystic Fibrosis, Hypertension, Portal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
measure of endothelial functionOther
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 sampleBiological
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 elastographyOther
Hepatic elastography by Fibrocan®. Patient should neither eat nor drink at least 2 hours before exam. 10 successive measurements are made.
Injected abdominal CTDiagnostic 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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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®). Receives: Other: measure of endothelial function; Biological: Blood sample; Other: Hepatic elastography |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 30 minutes
Secondary outcomes (4)
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).
Measured: 30 minutes
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.
Measured: 30 minutes
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.
Measured: 30 minutes
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.
Measured: 30 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Aug 2016 (estimated)
- Study start18 Apr 2016
- Primary completionDec 2021 (estimated)
- Study completionDec 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cystic FibrosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hopital Foch
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Dominique Grenet, MD, Principal investigator, Hopitral Foch
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02850692
- Sponsor's protocol ID
- 2015/33
- Other IDs
- 2015-A01872-47
- Acronym
- ENDOTH-MUCO
- Status last verified
- May 2020
- First submitted
- 16 Jun 2016
- Last updated
- 26 May 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Portal Hypertension and Systemic Endothelial Function: Investigation of Systemic Endothelial Dysfunction in Case of Portal Hypertension Associated With Cystic Fibrosis.
- ClinicalTrials.gov ID
- NCT02850692
- Acronym / sponsor ID
- ENDOTH-MUCO / 2015/33
- Conditions
- Cystic Fibrosis, Portal Hypertension
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Hopital FochUniversity, hospital or other
- Study start
- 18 Apr 2016 (actual)
- Primary completion
- Dec 2021 (estimated)
- Study completion
- Dec 2021 (estimated)
- First posted
- 1 Aug 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Cystic fibrosis with portal hypertension | Experimental | Other: measure of endothelial function, Biological: Blood sample, Other: Hepatic elastography, Diagnostic Test: Injected abdominal CTMucoviscidosis with portal hypertension. Blood sample (21ml). Hepatic elastography (Fibroscan®). Measure of endothelial function (Endopat®). Injected abdominal CT scan. |
| Muco without portal hypertension | Experimental | Other: measure of endothelial function, Biological: Blood sample, Other: Hepatic elastography, Diagnostic Test: Injected abdominal CTMucoviscidosis without portal hypertension. Blood sample (21ml). Hepatic elastography (Fibroscan®). Measure of endothelial function (Endopat®). Injected abdominal CT scan. |
| Portal hypertension without muco | Experimental | Other: measure of endothelial function, Biological: Blood sample, Other: Hepatic elastography, Diagnostic Test: Injected abdominal CTPortal hypertension without Mucoviscidosis. Blood sample (21ml) . Hepatic elastography (Fibroscan®). Measure of endothelial function (Endopat®). Injected abdominal CT scan. |
| Healthy volunteers | Experimental | Other: measure of endothelial function, Biological: Blood sample, Other: Hepatic elastographyHealthy volunteers. Blood sample (21ml) . Hepatic elastography (Fibroscan®). Measure of endothelial function (Endopat®). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (12 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| measure of endothelial functionArterial 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. | Other | Cystic fibrosis with portal hypertension, Healthy volunteers, Muco without portal hypertension, Portal hypertension without muco |
| Blood sample21 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. | Biological | Cystic fibrosis with portal hypertension, Healthy volunteers, Muco without portal hypertension, Portal hypertension without muco |
| Hepatic elastographyHepatic elastography by Fibrocan®. Patient should neither eat nor drink at least 2 hours before exam. 10 successive measurements are made. | Other | Cystic fibrosis with portal hypertension, Healthy volunteers, Muco without portal hypertension, Portal hypertension without muco |
| Injected abdominal CTPatient 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. | Diagnostic test | Cystic fibrosis with portal hypertension, Muco without portal hypertension, Portal hypertension without muco |
Primary outcome
Endothelial systemic function measured by EndoPAT®
Time frame: 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.
4 secondary outcomes
Serum levels of markers of endothelial dysfunction (tPA, thrombomodulin, Willebrandt factor, PAI1)
Time frame: 30 minutes
Endogline/Syndecan-4 ratio measurement
Time frame: 30 minutes
Measurement of hepatic elasticity by Fibroscan®
Time frame: 30 minutes
Hepatic abnormalities observed on injected abdominal CT.
Time frame: 30 minutes
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 May 2020.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dominique Grenet, MD principal investigator
Hopitral Foch
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing measure of endothelial function, Blood sample and Hepatic elastography in people with Cystic Fibrosis and Portal Hypertension, run by Hopital Foch at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 26 May 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Dominique Grenet, MD (33(0)146252582, d.grenet@hopital-foch.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Endothelial systemic function measured by EndoPAT® (time frame: 30 minutes). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 May 2020.