Alcoholic HepatitisRIHTANCT00388323
Adipose Tissue Involvement in Alcohol-induced Liver Inflammation in Human
A study testing blood and biopsies in people with Alcoholic Hepatitis and Alcoholic Cirrhosis, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
The histological characteristics of alcoholic liver disease (ALD) and non-alcoholic steatohepatitis (NASH) related to overweight and obesity suggest the presence of partly common physiopathological mechanisms. We reported that the ponderal overload was an independent risk factor of alcoholic cirrhosis. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Alcoholic Hepatitis, Alcoholic Cirrhosis
- What is being tested?
- blood and biopsies
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 47 participants
- Where
- 1 siteFrance
- Study dates
- Nov 2006to Jan 2011
- 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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Alcoholic patients of both sex aged from 18 to 75, hospitalized for alcoholic liver disease.
- HBs antigen negative, HIV negative, anti -VHC negative
- daily consumption exceeded 40-50 grams per day during the last year
- elevated AST level and liver biopsy during the hospitalisation Patients who signed the informed consent document
- patients affiliated to the national health insurance system
Who cannot join
- patients having another cause than alcohol for liver injury
- hepatocellular carcinoma or another developing cancer, severe associated pathology (cardiac disease, respiratory insufficiency, severe psychiatric problems), pancreatitis, infection, diabetes or a dyslipidemia
- patients treated with fibrates or other hypolipidaemic drugs, oral antidiabetics or insulin
- patients having hemostasis which does not permit the TRANSCOSTAL liver biopsy, platelet level <60 giga/l, or Quick test < 50 %, or (TCA higher than 1,5 times the time of the witness)
- patients refuse an adipose tissue biopsy
- patients treated with long-duration dose of clopidogrel (Plavix®)
- patients who significantly diminished alcohol consumption in comparison with the average consumption during the year preceding the inclusion
- patients not-affiliated to the national health insurance system
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Adipose Tissue Involvement in Alcohol-induced Liver Inflammation in Human : Study of Pro- and Anti-inflammatory Cytokines and ADIPOKINES..
The histological characteristics of alcoholic liver disease (ALD) and non-alcoholic steatohepatitis (NASH) related to overweight and obesity suggest the presence of partly common physiopathological mechanisms. We reported that the ponderal overload was an independent risk factor of alcoholic cirrhosis. The adipose tissue was considered for a long time as a simple place of storage of fat. However, it is now recognized that the adipose tissue can secrete cytokines called ADIPOKINES.
The adipose tissue can secrete others cytokines such as TNF-alpha, IL6, IL10 and IL1-Ra. Increase in the production of the leptin and TNF-alpha by the adipose tissue after alcohol administration in the rat, as well as the role of leptin in inflammation and liver fibrogenesis in the murine model of chemical hepatotoxicity strongly suggest that activation of adipocytes by alcohol can explain the strong correlation observed between the body mass index (BMI) and the severity of ethanol-induced liver injury. Conversely, it was suggested in a murine model that the reduction in adiponectin production would sensitize the liver with the toxicity of alcohol. The PPAR alpha and gamma are the receptors which play a role both in inflammation and glucide and lipid metabolism. Taking into account the inhibiting role of PPAR alpha on the proliferation of the hepatic stellate cells, responsible for the fibrosis, the PPAR could also be implied in the relation between the overweight and the hepatic fibrosis in the alcoholic.
Read the detailed description
The aim of this project is to demonstrate that ADIPOKINES, as well as the PPAR alpha and gamma are implied in the intensity of the steatosis and in the regulation of the inflammatory process and the hepatic fibrogenesis in alcoholic liver disease. In order to prove this hypothesis, we will study among patients having a ALD at various stages of histological severity: 1) the hepatic and subcutaneous abdominal adipose tissue expression of the PPAR alpha and PPAR gamma, 2) the hepatic and subcutaneous abdominal adipose tissue expression of the TNF alpha, the IL1Ra, the IL6 and the IL10, 3) the hepatic and subcutaneous abdominal adipose tissue expression of the ADIPOKINES (leptin, adiponectin, resistin), 4) the serum ADIPOKINES values, the cyanotic of the mRNA expression and of the serum ADIPOKINES values after 7 days of alcohol withdrawal 50 patients will be studied (25 having ALD without cirrhosis, with or without acute alcoholic hepatitis (AAH) and 25 having alcoholic cirrhosis with or without AAH). A part of liver biopsy will be frozen in a dry tube. The percutaneous adipose tissue will be obtained with a punction on the abdominal level at the time of inclusion of the patients having AAH and, for the second time, after 7 days of alcohol withdrawal, than will be frozen. The TNF alpha, the IL1Ra, the IL6, the IL10, the leptin, the adiponectin and the resistin expression as well as the hepatic and adipose tissue PPAR alpha and gamma will be evaluated by PCR in real time. The serum concentration of the ADIPOKINES (leptin, adiponectin, resistin) will be measured by ELISA or RIA.
If our hypothesis is true, severity of liver lesions (steatosis, AAH, fibrosis) could be positively correlated with the expression in the liver and the adipose tissue and / or the serum values of the anti-inflammatory cytokines and ADIPOKINES (TNF alpha, IL6, leptin, resistin) and negatively with the cytokines and ADIPOKINES which are potentially anti-inflammatory (IL1Ra, IL10, adiponectin). We also expect to find a negative correlation between the amount of hepatic and adipose tissue PPAR-alpha and PPAR-gamma mRNA and the severity of the liver disease.
- Conditions
- Alcoholic Hepatitis, Alcoholic Cirrhosis
- Being tested
- blood and biopsies
- Keywords
- Alcohol, Hepatitis, Cirrhosis, Inflammation, Cytokines, ADIPOKINES, Adipose tissue
- Medical subject headings
- Hepatitis, Alcoholic, Liver Cirrhosis, Alcoholic, Hepatitis, Fibrosis, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
blood and biopsiesOther
blood and biopsies
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Not described Receives: Other: blood and biopsies |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adipokines
To demonstrate that ADIPOKINES are implied in the intensity of the steatosis and in the regulation of the inflammatory process and the hepatic fibrogenesis in alcoholic liver disease.
Measured: at the inclusion and after one week
PPAR α et γ
To demonstrate that the PPAR α et γ are implied in the intensity of the steatosis and in the regulation of the inflammatory process and the hepatic fibrogenesis in alcoholic liver disease.
Measured: At the inclusion and after one week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Oct 2006 (estimated)
- Study startNov 2006
- Primary completionJan 2011
- Study completionJan 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Alcoholic HepatitisStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- 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
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 47 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Gabriel PERLEMUTER, MD, Principal investigator, Hôpital Antoine Béclère - Clamart - FRANCE
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00388323
- Sponsor's protocol ID
- P 051041
- Other IDs
- AOR 05049
- Acronym
- RIHTA
- Status last verified
- Nov 2012
- First submitted
- 13 Oct 2006
- Last updated
- 11 Dec 2012
- Results posted
- No
- Data monitoring committee
- No
Publications
Voican CS, Njike-Nakseu M, Boujedidi H, Barri-Ova N, Bouchet-Delbos L, Agostini H, Maitre S, Prevot S, Cassard-Doulcier AM, Naveau S, Perlemuter G. Alcohol withdrawal alleviates adipose tissue inflammation in patients with alcoholic liver disease. Liver Int. 2015 Mar;35(3):967-78. doi: 10.1111/liv.12575. Epub 2014 Jun 3.
PubMed 24766056
Study at a glance
From the registry record, last updated by the sponsor on 11 Dec 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Adipose Tissue Involvement in Alcohol-induced Liver Inflammation in Human : Study of Pro- and Anti-inflammatory Cytokines and ADIPOKINES..
- ClinicalTrials.gov ID
- NCT00388323
- Acronym / sponsor ID
- RIHTA / P 051041
- Conditions
- Alcoholic Hepatitis, Alcoholic Cirrhosis
- Keywords
- Alcohol, Hepatitis, Cirrhosis, Inflammation, Cytokines, ADIPOKINES, Adipose tissue
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 47 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- Nov 2006
- Primary completion
- Jan 2011 (actual)
- Study completion
- Jan 2011 (actual)
- First posted
- 16 Oct 2006 (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.
The histological characteristics of alcoholic liver disease (ALD) and non-alcoholic steatohepatitis (NASH) related to overweight and obesity suggest the presence of partly common physiopathological mechanisms. We reported that the ponderal overload was an independent risk factor of alcoholic cirrhosis. The adipose tissue was considered for a long time as a simple place of storage of fat. However, it is now recognized that the adipose tissue can secrete cytokines called ADIPOKINES.
The adipose tissue can secrete others cytokines such as TNF-alpha, IL6, IL10 and IL1-Ra. Increase in the production of the leptin and TNF-alpha by the adipose tissue after alcohol administration in the rat, as well as the role of leptin in inflammation and liver fibrogenesis in the murine model of chemical hepatotoxicity strongly suggest that activation of adipocytes by alcohol can explain the strong correlation observed between the body mass index (BMI) and the severity of ethanol-induced liver injury. Conversely, it was suggested in a murine model that the reduction in adiponectin production would sensitize the liver with the toxicity of alcohol. The PPAR alpha and gamma are the receptors which play a role both in inflammation and glucide and lipid metabolism. Taking into account the inhibiting role of PPAR alpha on the proliferation of the hepatic stellate cells, responsible for the fibrosis, the PPAR could also be implied in the relation between the overweight and the hepatic fibrosis in the alcoholic.
Detailed description
The aim of this project is to demonstrate that ADIPOKINES, as well as the PPAR alpha and gamma are implied in the intensity of the steatosis and in the regulation of the inflammatory process and the hepatic fibrogenesis in alcoholic liver disease. In order to prove this hypothesis, we will study among patients having a ALD at various stages of histological severity: 1) the hepatic and subcutaneous abdominal adipose tissue expression of the PPAR alpha and PPAR gamma, 2) the hepatic and subcutaneous abdominal adipose tissue expression of the TNF alpha, the IL1Ra, the IL6 and the IL10, 3) the hepatic and subcutaneous abdominal adipose tissue expression of the ADIPOKINES (leptin, adiponectin, resistin), 4) the serum ADIPOKINES values, the cyanotic of the mRNA expression and of the serum ADIPOKINES values after 7 days of alcohol withdrawal 50 patients will be studied (25 having ALD without cirrhosis, with or without acute alcoholic hepatitis (AAH) and 25 having alcoholic cirrhosis with or without AAH). A part of liver biopsy will be frozen in a dry tube. The percutaneous adipose tissue will be obtained with a punction on the abdominal level at the time of inclusion of the patients having AAH and, for the second time, after 7 days of alcohol withdrawal, than will be frozen. The TNF alpha, the IL1Ra, the IL6, the IL10, the leptin, the adiponectin and the resistin expression as well as the hepatic and adipose tissue PPAR alpha and gamma will be evaluated by PCR in real time. The serum concentration of the ADIPOKINES (leptin, adiponectin, resistin) will be measured by ELISA or RIA.
If our hypothesis is true, severity of liver lesions (steatosis, AAH, fibrosis) could be positively correlated with the expression in the liver and the adipose tissue and / or the serum values of the anti-inflammatory cytokines and ADIPOKINES (TNF alpha, IL6, leptin, resistin) and negatively with the cytokines and ADIPOKINES which are potentially anti-inflammatory (IL1Ra, IL10, adiponectin). We also expect to find a negative correlation between the amount of hepatic and adipose tissue PPAR-alpha and PPAR-gamma mRNA and the severity of the liver disease.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Other: blood and biopsies |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Alcoholic patients of both sex aged from 18 to 75, hospitalized for alcoholic liver disease.
- HBs antigen negative, HIV negative, anti -VHC negative
- daily consumption exceeded 40-50 grams per day during the last year
- elevated AST level and liver biopsy during the hospitalisation Patients who signed the informed consent document
- patients affiliated to the national health insurance system
Key exclusion criteria (8 listed)
- patients having another cause than alcohol for liver injury
- hepatocellular carcinoma or another developing cancer, severe associated pathology (cardiac disease, respiratory insufficiency, severe psychiatric problems), pancreatitis, infection, diabetes or a dyslipidemia
- patients treated with fibrates or other hypolipidaemic drugs, oral antidiabetics or insulin
- patients having hemostasis which does not permit the TRANSCOSTAL liver biopsy, platelet level <60 giga/l, or Quick test < 50 %, or (TCA higher than 1,5 times the time of the witness)
- patients refuse an adipose tissue biopsy
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 |
|---|---|---|
| blood and biopsiesblood and biopsies | Other | 1 |
Primary outcome
Adipokines
Time frame: at the inclusion and after one week
To demonstrate that ADIPOKINES are implied in the intensity of the steatosis and in the regulation of the inflammatory process and the hepatic fibrogenesis in alcoholic liver disease.
PPAR α et γ
Time frame: At the inclusion and after one week
To demonstrate that the PPAR α et γ are implied in the intensity of the steatosis and in the regulation of the inflammatory process and the hepatic fibrogenesis in alcoholic liver disease.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Dec 2012.
- Derived from this study: PubMed 24766056Voican CS, Njike-Nakseu M, Boujedidi H, Barri-Ova N, Bouchet-Delbos L, Agostini H, Maitre S, Prevot S, Cassard-Doulcier AM, Naveau S, Perlemuter G. Alcohol withdrawal alleviates adipose tissue inflammation in patients with alcoholic liver disease. Liver Int. 2015 Mar;35(3):967-78. doi: 10.1111/liv.12575. Epub 2014 Jun 3.
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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.
Gabriel PERLEMUTER, MD principal investigator
Hôpital Antoine Béclère - Clamart - FRANCE
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing blood and biopsies in people with Alcoholic Hepatitis and Alcoholic Cirrhosis, run by Assistance Publique - Hôpitaux de Paris 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 5 inclusion and 8 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: finished, as of the sponsor's last update on 11 Dec 2012. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Adipokines (time frame: at the inclusion and after one week). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00388323, which also lists 1 linked publication.
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 11 Dec 2012.