Identification of Biomarkers Related to Liver Fibrosis as New Therapeutic Targets

Fibrosis Clinical Trial

— FIBROTHER  

Official title:

Identification of Biomarkers Related to Liver Fibrosis as New Therapeutic Targets

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03979417
• Other study ID #: 2018-069
• Status: Completed
• Start date: September 30, 2019
• Est. completion date: October 26, 2022

Study information

• Verified date: March 2022
• Source: Institut Pasteur
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Fibrosis is a dynamic process resulting from the balance of fibrogenesis and fibrolysis, mainly secondary to chronic necro-inflammation related to regular alcohol consumption, metabolic syndrome (NASH) or viral hepatitis. The liver has the property of allowing the reversion of fibrosis / cirrhosis when the necrotic-inflammatory activity is controlled. The balance between fibrosis / fibrolysis and its inhibition depends on many pathways and the hypothesis of the efficacy of a single treatment remains uncertain. Molecular factors in the progression of liver fibrosis should be determined. It is necessary to control the liver fibrosis and thus reduce the risk of carcinoma in this population. The anti-fibrotic drugs are being developed, but so far only alpha-tocopherol and obeticholic acid have been shown to have a significant anti-fibrotic effect in humans. Several new drugs are currently being evaluated in ongoing Phase 2 and 3 randomized clinical trials, but most of them have intrinsic limitations: (i) they take a long time for evaluation (> 3 years), ( ii) they generally require an histopathological evaluation by serial liver biopsies that are invasive and unpopular with patients who are aware of noninvasive tests for fibrosis assessment and (iii) treatment is often a single treatment versus a placebo group with the uncertainty that at 1 or 3 years, serial liver biopsies results are convincing.

Description:

The study will be performed in 30 patients. Patients will be enrolled in two investigators sites (Cochin Hospital, Pitie-Salpetriere Hospital, France) where the patient selection will be conducted during a Multidisciplinary Collaborative Meeting. The patients will be enrolled after collecting their informed consent. As soon as the patient is included, arrangements will be made for the organization of the liver resection according to the usual procedure of the hospital department. The biological samples for the research (blood and liver) will be taken at the time of the surgery and sent to the Research Unit (Institut Pasteur) where immunological analyses will be carried out.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: October 26, 2022
• Est. primary completion date: September 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients > 18 years
• Patients with primary liver disease or liver metastases
• Patients undergoing liver resection

Exclusion Criteria:

• Presence of Human Immunodeficiency Virus (HIV) infection
• Presence of Human T Leukemia Virus (HTLV) infection
• Taking immunosuppressive drugs in the 6 months prior to surgery
• A person deprived of liberty by judicial or administrative decision

Related Conditions & MeSH terms

• Fibrosis
• Hepatopathy
• Liver Cirrhosis

Intervention

Other:
• Blood draw and liver resection
The samples are transferred to the research unit for immunological studies.

Locations

Country	Name	City	State
France	Cochin Hospital	Paris
France	Pitie-Salpetriere Hospital	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Institut Pasteur

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Identification of biomarkers of liver fibrosis	Frequency of cell receptors (CD4, CD8, NK, MAIT, etc.) in whole blood and liver (measured by FACS). A comparison will be made in each of the 3 groups (F0-F1, F2-F3, F4) and between the three groups.	Baseline
Secondary	Transcription factors	Frequency of transcription factors (Stat1, Stat3, Foxp3, etc.) in whole blood and liver (measured by FACS). A comparison will be made in each of the 3 groups (F0-F1, F2-F3, F4) and between the three groups.	Baseline
Secondary	Evaluation of anti-fibrotic properties of biomarkers	Monitoring the properties by different techniques (ELISA, Nanostring, Immunoblotting). A comparison will be made in each of the 3 groups (F0-F1, F2-F3, F4) and between the three groups.	Baseline