Microparticles in Cirrhosis and Portal Hypertension

Liver Cirrhosis Clinical Trial

— MicroCir  

Official title:

Characterization of Microparticles in Cirrhosis and Portal Hypertension With Implications

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02859610
• Other study ID #: 2013-A01258-37
• Status: Completed
• Phase: N/A
• First received: July 28, 2016
• Last updated: August 4, 2016
• Start date: January 2014
• Est. completion date: January 2015

Study information

• Verified date: July 2016
• Source: Centre Hospitalier Universitaire de Besancon
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Committee for the Protection of PersonnesFrance: The Commission nationale de l’informatique et des libertés
• Study type: Interventional

Clinical Trial Summary

research on interactions between portal hypertension and microparticles

Description:

It has already been shown that increased certain markers of stress, such as prolonged elevation of CRP in the absence of bacterial infection, increased free cortisol and serum copeptin, are associated with an excess of mortality in cirrhosis.

MPs are membrane vesicles of variable size between 0.1 and 1 .mu.m, released into the extracellular space following activation or cellular apoptosis. MPs are also found in the circulating blood of healthy volunteers and their plasma levels rise in certain diseases to increased thrombotic risk, such as in cancer. Their membrane is composed of antigens whose organization is characteristic of the parent cell and negatively charged phospholipids, phosphatidylserines, conferring pro-coagulant properties to these MPs.

Currently, work on the MPs are increasing following the discovery of their involvement in physiological processes such as proliferation, differentiation, cell activation and immune response but it is certainly their pro-thrombogenic power that was the most studied.

Recent studies have also implicated MPs in the pathophysiology of chronic liver disease. Cirrhotic patients have elevated concentrations of MPs from leukocytes, endothelial cells and hepatocytes compared to control subjects, and concentrations of MPs increase with worsening liver function. Increasing MPs during the cirrhosis may be related on the one hand with a decreased clearance and secondly with an excess of proinflammatory cytokines by increasing the phenomenon of intestinal bacterial translocation. The assumption of the role of systemic inflammation in the training of MPs is reinforced by the existence of a significant correlation between the original MPs hepatocyte or buffy endothelial and CRP Thus, the increase in MPs observed with the increase of PH could increase the risk of thrombosis in intestinal microcirculation leading to enterocytic suffering from ischemic, reflected by an increase in serum concentrations of I-FABP ( intestinal fatty acid binding protein). This suffering enterocytes leads to increased intestinal bacterial translocation and ultimately to increased formation of MPs. These MPs could also worsen liver function by the same phenomenon of thrombosis in the hepatic microcirculation.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: January 2015
• Est. primary completion date: January 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Non infected cirrhotic patient (30 patients Child-Pugh A, 30 Child-Pugh B et 30 Child-Pugh C).

• 10 heathly volunteer (groupe contrôle).

Exclusion Criteria:

• legal incapacity or limited legal capacity

• Subject unlikely to cooperate in the study and / or low early cooperation by the investigator

• Subject without health insurance

• Pregnant woman

• About being in the disqualification of another study or under the "national register of volunteers."

• Any proven or suspected infection

• Pre-hepatic portal hypertension (door thrombosis) or post-liver (Budd-Chiari) transplant patients, HIV infection (also refusing HIV status) or patients on immunosuppressive therapies (including corticosteroids) interferon taken

• Treatment with anticoagulants or antiplatelet upper gastrointestinal bleeding in the two months prior

• Patients with TIPS

• Any cancer pathology proven and current.

• Chronic heart failure (stage III or IV of the classification of the New York Heart Association [NYHA])

• Inability to receive clear information in patients with severe encephalopathy and do not have someone you trust

Study Design

Allocation: Non-Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Fibrosis
• Hypertension
• Hypertension, Portal
• Liver Cirrhosis
• Portal Hypertension

Intervention

Other:
• research on interactions between portal hypertension and microparticles

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire de Besancon

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Level of expression of microparticles in cirrhotic patients with hepatic function of varying severity (Child- Pugh A to C) and in 10 healthy controls.		one year	No
Primary	Procoagulant activity of microparticles in cirrhotic patients with hepatic function of varying severity (Child- Pugh A to C) and in 10 healthy controls.		one year	No