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Characterization of Immune Semaphorin in Non Alcoholic Fatty Liver Disease and NASH

Primary Purpose

Non Alcoholic Fatty Liver Disease

Status
Completed
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
Evaluation of the staging of fibrosis liver
Determine the expression level of semaphorin
Determination of the composition of immunity cells
Sponsored by
Centre Hospitalier Universitaire de Nice
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Non Alcoholic Fatty Liver Disease

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Morbid obese patients

Inclusion Criteria:

  • Male and female aged 18-65 years
  • Patients with body mass index justifying a surgery for obesity (BMI ≥ 40 kg / m2 or BMI ≥ 35 kg / m2 with comorbidities)
  • Consumption of alcohol <20 g / d
  • Patients affiliated to a social security insurance
  • Patients who signed the informed consent

Exclusion Criteria:

  • Hemochromatosis
  • Toxic hepatitis
  • Deficiency of alpha-1-antitrypsin
  • Wilson's disease
  • Liver Autoimmune disease (primary biliary cirrhosis, autoimmune hepatitis)
  • Hepatitis B, C
  • Drug-induced hepatitis
  • Presence of HIV status
  • Corticosteroids, amiodarone, valproic acid, tamoxifen, anti-inflammatory drugs, lipid lowering agents, testosterone agonists or beta-adrenergic antagonists, orlistat.
  • Pregnant or breastfeeding women
  • Incarcerated patients or patient under guardianship

Sites / Locations

  • Service d'Hépato-Gastroentérologie - Hôpital de l'Archet

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Other

Other

Other

Arm Label

Morbid obese patients

Control patients

Patients with overweight, steatosis and steatohepatitis

Arm Description

Outcomes

Primary Outcome Measures

Evaluation of the staging of liver fibrosis
The investigators determine the stage of liver fibrosis by histological study of biopsies
Determination of the expression of level of semaphorin
The investigators determine by technic of Reverse Transcription Polymerase Chain Reaction (RT-PCR) the expression of level of semaphorin
Determination of the composition of immunity cells
The investigators determine the composition of immunity cells by Immunohistochemical and biochemical analyses (Western Blotting)

Secondary Outcome Measures

Full Information

First Posted
June 20, 2016
Last Updated
October 3, 2017
Sponsor
Centre Hospitalier Universitaire de Nice
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1. Study Identification

Unique Protocol Identification Number
NCT02820285
Brief Title
Characterization of Immune Semaphorin in Non Alcoholic Fatty Liver Disease and NASH
Official Title
Characterization of Immune Semaphorin in Non Alcoholic Fatty Liver Disease and NASH
Study Type
Interventional

2. Study Status

Record Verification Date
June 2016
Overall Recruitment Status
Completed
Study Start Date
March 2013 (undefined)
Primary Completion Date
September 2016 (Actual)
Study Completion Date
September 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Centre Hospitalier Universitaire de Nice

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
Recent epidemiological studies in France showed a high prevalence of obesity (14.5%) and its strong increase in the last 20 years. Among the many complications associated with obesity, liver complications (steatosis and steatohepatitis [NASH]) are among the most common. Semaphorins were described in the early 1990. More than 20 types of these proteins have been reported to date. These proteins were used for neural development. Since many functions have also been described. The semaphorins are involved in numerous physiological or physiopathological processes (cardiac morphogenesis, vascular growth, tumor progression), the regulation of immune cells and liver fibrosis. Preliminary studies have allowed to show that dendritic cells infiltrate adipose tissue and initiate the activation of T cells and inflammation. Immune semaphorin are new players in the regulation of inflammation and immune reactions. The role of immune semaphorin in regulating inflammation in the two compartments (liver and adipose tissue) could be a crucial step that could lead to more severe liver damage. Its dysregulation could explain NASH injuries. The goal is to identify a new mode of regulation of cellular homeostasis in the fatty liver disease. These factors may serve as diagnostic markers or future therapeutic targets.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non Alcoholic Fatty Liver Disease

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
148 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Morbid obese patients
Arm Type
Other
Arm Title
Control patients
Arm Type
Other
Arm Title
Patients with overweight, steatosis and steatohepatitis
Arm Type
Other
Intervention Type
Other
Intervention Name(s)
Evaluation of the staging of fibrosis liver
Intervention Description
The investigators will determine the severity of steatosis, inflammation and fibrosis by histological study of liver biopsies
Intervention Type
Other
Intervention Name(s)
Determine the expression level of semaphorin
Intervention Description
The investigators will determine the expression level (gene and protein) of immune semaphorin and their (s) receptor (s) in the liver and subcutaneous and visceral adipose tissue by RT-PCR,
Intervention Type
Other
Intervention Name(s)
Determination of the composition of immunity cells
Intervention Description
The investigators determine the composition of immunity cells by immunohistochemical and biochemical analyses (Western Blotting )
Primary Outcome Measure Information:
Title
Evaluation of the staging of liver fibrosis
Description
The investigators determine the stage of liver fibrosis by histological study of biopsies
Time Frame
Day 0
Title
Determination of the expression of level of semaphorin
Description
The investigators determine by technic of Reverse Transcription Polymerase Chain Reaction (RT-PCR) the expression of level of semaphorin
Time Frame
Day 0
Title
Determination of the composition of immunity cells
Description
The investigators determine the composition of immunity cells by Immunohistochemical and biochemical analyses (Western Blotting)
Time Frame
Day 0

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Morbid obese patients Inclusion Criteria: Male and female aged 18-65 years Patients with body mass index justifying a surgery for obesity (BMI ≥ 40 kg / m2 or BMI ≥ 35 kg / m2 with comorbidities) Consumption of alcohol <20 g / d Patients affiliated to a social security insurance Patients who signed the informed consent Exclusion Criteria: Hemochromatosis Toxic hepatitis Deficiency of alpha-1-antitrypsin Wilson's disease Liver Autoimmune disease (primary biliary cirrhosis, autoimmune hepatitis) Hepatitis B, C Drug-induced hepatitis Presence of HIV status Corticosteroids, amiodarone, valproic acid, tamoxifen, anti-inflammatory drugs, lipid lowering agents, testosterone agonists or beta-adrenergic antagonists, orlistat. Pregnant or breastfeeding women Incarcerated patients or patient under guardianship
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Albert TRAN, MDPhD
Organizational Affiliation
Centre Hospitalier Universitaire de Nice
Official's Role
Principal Investigator
Facility Information:
Facility Name
Service d'Hépato-Gastroentérologie - Hôpital de l'Archet
City
Nice
ZIP/Postal Code
06003
Country
France

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
28550439
Citation
Sans A, Bailly L, Anty R, Sielezenef I, Gugenheim J, Tran A, Gual P, Iannelli A. Baseline Anthropometric and Metabolic Parameters Correlate with Weight Loss in Women 1-Year After Laparoscopic Roux-En-Y Gastric Bypass. Obes Surg. 2017 Nov;27(11):2940-2949. doi: 10.1007/s11695-017-2720-8. Erratum In: Obes Surg. 2017 Jul 5;:
Results Reference
derived

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Characterization of Immune Semaphorin in Non Alcoholic Fatty Liver Disease and NASH

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