Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05895890
Other study ID # 200312
Secondary ID 2019-A01331-56
Status Recruiting
Phase
First received
Last updated
Start date October 1, 2022
Est. completion date February 1, 2053

Study information

Verified date July 2023
Source Assistance Publique - Hôpitaux de Paris
Contact Cosmin Voican, Dr
Phone 01 45 37 47 75
Email cosmin.voican@aphp.fr
Is FDA regulated No
Health authority
Study type Observational

Clinical Trial Summary

Excessive alcohol consumption is a major public health problem, particularly in France. It is the leading cause of cirrhosis and hepatocellular carcinoma. Among subjects with heavy alcohol consumption, the majority of patients develop fatty liver overload (steatosis), but only 10 to 35% develop acute alcoholic hepatitis (AAH) and 8 to 20% progress to cirrhosis. Steatosis is the earliest lesion, rapidly reversible after abstinence from alcohol. On the other hand, the occurrence of AAH leads to a strong progression of fibrosis. The investigators have shown on serial liver biopsies that a subgroup of heavy drinkers develop episodes of AAH and progress to cirrhosis. Therefore, factors other than the amount of alcohol consumed alone influence the development and progression of alcoholic liver disease (ALD). Among these factors, it is now accepted that the gut microbiome plays an important role in the pathogenesis of ALD. Increased intestinal permeability and activation of the innate immune system by lipolysaccharide (LPS) of digestive origin is a key factor in the initiation of AAH. The alteration of the intestinal barrier induced by alcohol abuse seems to involve dysbiosis. Furthermore, the investigatorshave shown that the sensitivity of the liver to alcohol toxicity is transmissible from humans to mice via the gut microbiome. Despite these advances, the causal relationship between mycobiome disruption and ALD in humans requires confirmation in prospective studies. The intestinal microbiome represents all the microorganisms found in the digestive tract: bacteria (bacterial microbiome), viruses (virome), fungi (mycobiome). Recent data point to the role of disturbances of the mycobiome and the virome in human pathology. The intestinal virome consists of two major types of viruses: eukaryotic RNA and DNA viruses that infect host cells and prokaryotic or bacteriophage viruses that infect the bacterial microbiome. Recent evidence suggests that the virome participates in immune system homeostasis. Infection of axenic mice with murine norovirus restores the functionality of intestinal lymphocytes. However, the involvement of the intestinal virome in ALD has never been studied. Cessation of alcohol consumption has a beneficial effect in all stages of ALD . It reduces the risk of complications of cirrhosis and, for early stages of liver damage, prevents progression to advanced stages (severe AAH and cirrhosis). Unfortunately, most patients with alcohol addiction do not achieve long-term abstinence or significant reduction in their consumption despite psychological and medical support. Depression and anxiety are also associated with gut dysbiosis in humans. The causal role, at least partial, of this dysbiosis in addictive phenomena, whether alcohol or other addictions such as cocaine, has been shown. Thus, the modification of MI influences the addictive behavior of cocaine-dependent mice (. All these data show the major role of the microbiota-central nervous system (CNS) axis in mental disorders such as alcohol addiction and its consequences (craving, depression, anxiety). This interaction is mediated by several mechanisms such as the production of active metabolites by the intestinal microbiome and the translocation of bacteria or bacterial derivatives. Primary Objective: To characterize temporal changes in the gut microbiome (bacterial, viral, and fungal) within sequential specimens (stool, saliva, serum) prior to the occurrence of acute alcoholic hepatitis episodes Secondary Objectives: - Demonstrate that specific fecal, serum, or saliva microbiome profiles (bacterial, viral, and fungal) can predict the progression of alcoholic liver disease to severe alcoholic hepatitis, fibrosis, and cirrhosis. - Characterize changes in the composition of the gut microbiome (bacterial, viral and fungal) associated with the progression of alcoholic liver disease to severe alcoholic hepatitis and cirrhosis. - Characterize the changes in the microbiome during alcohol withdrawal. - Identify microbiome profiles associated with alcohol dependence and anxiety-depressive events related to alcohol addiction. - To identify bacterial species with a protective effect in alcoholic liver disease. - To identify beneficial bacterial species against alcohol dependence. - To study the microbiome-host interaction in alcoholic liver disease and alcohol addiction. - To identify microbiome profiles with prognostic value in severe alcoholic hepatitis and alcoholic cirrhosis. Number of centers: 7 Number of subjects expected 1000 Population concerned: The study will include a population of patients with excessive alcohol consumption seen in consultation or hospitalized for alcohol addiction problems and/or exploration of alcohol-related liver damage Inclusion period: January 2020 - January 2030 Patient observation period: 5 to 20 years Study duration: 30 years


Recruitment information / eligibility

Status Recruiting
Enrollment 1000
Est. completion date February 1, 2053
Est. primary completion date February 1, 2043
Accepts healthy volunteers No
Gender All
Age group 18 Years to 75 Years
Eligibility Inclusion Criteria: - Age between 18 and 75 years - Average alcohol consumption of more than 20 g per day in women and 30 g per day in men during the previous year; - Patients seen in consultation or hospitalized for assessment of alcoholic liver disease and management of alcohol addiction; - Having given their consent to participate in this study; - Affiliated to a social security system (beneficiary or beneficiary's right). Exclusion Criteria: - Antibiotic, probiotic or prebiotic treatment within the previous 3 months ; - Digestive hemorrhage, acute pancreatitis, acute or chronic diarrhea (except diarrhea related to excessive alcohol consumption) or chronic inflammatory bowel disease; - Another cause of liver damage; - A serious associated pathology (respiratory failure, heart failure, severe psychiatric disorders, active cancer). - Patient under guardianship or curatorship

Study Design


Intervention

Genetic:
Sequential sampling (stool, saliva, serum) .
Sequential sampling (stool, saliva, serum) prior to the occurrence of AAH episodes in heavy drinking patients to identify protective or deleterious profiles.

Locations

Country Name City State
France Cosmin Voican Clamart Ile De France

Sponsors (1)

Lead Sponsor Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type Measure Description Time frame Safety issue
Primary Temporal changes in the gut microbiome Differences in gut microbiome composition between inclusion and different follow-up visits every 6 months until 240 months
Secondary Differences in gut microbiome composition as a function of the rate of progression of liver fibrosis Differences in the composition of the gut microbiome, analyzed using the metagenomic technique, the rate of progression of liver fibrosis, as measured by median elasticity (kPa/year) every 6 months until 240 months
Secondary Differences in gut microbiome composition at inclusion between patients with and without the development of severe acute alcoholic hepatitis or cirrhosis between inclusion and different follow-up visits. Differences in the composition of the gut microbiome, analyzed using the metagenomic technique every 6 months until 240 months
Secondary Differences in gut microbiome composition at baseline between failed and weaned patients and between baseline and follow-up visits. Differences in the composition of the gut microbiome, analyzed using the metagenomic technique, every 6 months until 240 months
Secondary Differences in gut microbiome composition as a function of craving intensity, depression and anxiety. Differences in the composition of the gut microbiome, analyzed using the metagenomic technique every 6 months until 240 months
Secondary The correlation between gut microbiome, host genotype and FAD severity. Differences in the composition of the gut microbiome, analyzed using the metagenomic technique every 6 months until 240 months
Secondary Effect of bacteria identified as beneficial, on mouse models of alcoholic liver disease, depression and anxiety. Differences in the composition of the gut microbiome, analyzed using the metagenomic technique every 6 months until 240 months
Secondary The association between the gut microbiome and the prognosis of patients with acute alcoholic hepatitis or cirrhosis. Differences in the composition of the gut microbiome, analyzed using the metagenomic technique every 6 months until 240 months
See also
  Status Clinical Trial Phase
Completed NCT00708617 - FIBROSCAN Validation and Interest of Fibrotest - FIBROSCAN Association for Fibrosis Diagnosis in Alcoholic Liver Disease N/A
Completed NCT00990639 - Effect of Candesartan in Alcoholic Liver Fibrosis Phase 1/Phase 2
Recruiting NCT04106518 - Study of Genetic Determinants in Alcoholic Hepatitis and Establishment of a Multicenter Prospective Cohort of Patients With Alcoholic Liver Disease
Recruiting NCT04666402 - Integrated Diagnostics for Early Diagnosis of Liver Disease
Recruiting NCT02331745 - RCT Study on Granulocyte Colony-stimulating Factor(G-CSF) Treatment of Hepatic Failure Phase 4
Completed NCT01501162 - Effect of Probiotics on Gut-Liver Axis of Alcoholic Liver Disease Phase 4
Completed NCT04557774 - Cognitive Function of Alcoholic Compensated Liver Cirrhosis
Recruiting NCT03267069 - Evaluating Alcohol Use in Alcoholic Liver Disease
Recruiting NCT03295812 - Stratification of Chronic Alcoholic Liver Diseases (SCALE Study) N/A
Recruiting NCT05855031 - The Liver Care Trial N/A
Not yet recruiting NCT03503708 - Herbal Supplements for Improvement of Liver Function in Participants With Alcoholic Liver Disease N/A
Completed NCT02796469 - Meta-Analysis of Drug Therapy in Patients With Severe Alcoholic Hepatitis N/A
Completed NCT02140294 - Long Term Effect of Aggressive Nutritional Management on Survival in Patients With Alcoholic Liver Disease N/A
Recruiting NCT03209791 - Ethanol Induces Skeletal Muscle Autophagy
Recruiting NCT04736966 - Guselkumab (Anti-IL 23 Monoclonal Antibody) for Alcohol Associated Liver Disease Phase 1
Recruiting NCT04400604 - Study of Alcohol-related Liver Disease in Europe
Completed NCT03402256 - Text Messaging to Reduce Alcohol Relapse in Liver Transplant Patients N/A
Completed NCT01711125 - Baclofen in the Treatment of Alcohol Dependence With or Without Alcoholic Liver Disease Phase 3
Active, not recruiting NCT03863730 - Profermin®: Prevention of Progression in Alcoholic Liver Disease by Modulating Dysbiotic Microbiota N/A
Not yet recruiting NCT06307964 - Intra-Hepatic Microbiota in Alcoholic Hepatitis