Intestinal Microbiota Profiling in Severe Acute Alcoholic Hepatitis Patients (HepatAlc-IM)

December 5, 2023 updated by: Centre Hospitalier Universitaire, Amiens

Intestinal Microbiota Profiling in HAA Patients

In humans, alcohol-related dysbiosis exists with a decrease in bacteroides. This dysbiosis is responsible for the breakdown of the intestinal barrier by a decrease in the synthesis of protective mucus, and some proteins involved in tight junctions or a decrease in defensin (Reg3b, Reg3g) which promotes bacterial growth and ultimately bacterial translocation. The microbiota of a patient with alcoholic hepatitis is different from that of a patient without alcoholic hepatitis. Acute alcoholic hepatitis has a severe prognosis and corticosteroids are the only first line therapy option, with better survival at 28 days versus placebo. However, mortality remains high at 30% at 3 months, which highlights the importance of seeking intestinal microbiota profile on treatment response.

The determination of one or more intestinal microbiota signatures associated with the treatment response Corticosteroids plus FMT or Corticosteroids plus placebo will allow the clinician to have a simple and rapid test obtained in 16S RNA analysis to predict the therapeutic response and potentially the best treatment to adopt and to address medical and medico-economic stakes.

The investigators will first characterize the alcohol-induced dysbiosis by a whole microbiota sequencing in the different groups. Specific bacterial species identify by DNA sequencing should be confirmed by qPCR of 16S rDNA to determine a fingerprint of sAH microbiota. Metabolic properties of intestinal microbiota, such as production of short chain fatty acids, will be analyzed by using HPLC. In the sAH group, evolution of intestinal microbiota will be observed by shotgun DNA sequencing between the day 0 and the day 7 of corticosteroids treatment.

The analysis of sAH patients' microbiota (day 0) will allow us to obtain a non-responder profile to corticosteroids that can be used as a prognostic marker to use in the clinic. The deliverable is the bacterial fingerprint of the treatment response and its valuation is its use as a predictive tool of the response.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

200

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Patients aged from 18 to 75 years, having :
  • Heavy drinker with Maddrey Score ≥ 32 : PT(second)-PT(control)x4.6+Bilirubine (mg/dl)
  • Histological confirmed Alcoholic hepatitis
  • Personal consent signed to the trial
  • No exclusion criteria

Exclusion Criteria:

  • Age < 18 years and/or > 75 years,
  • Pregnancy or lactating females,
  • No personal consent
  • Other causes of liver disease: chronic hepatitis B (antigen HBs positive), hepatitis C (HCV RNA positive), acetaminophen hepatotoxicity, biliary obstruction, autoimmune hepatitis, primary biliary cholangitis, primary sclerosis cholangitis, alpha 1 antitrypsine deficiency, and Wilson disease.
  • Uncontrolled liver complications:
  • Upper gastrointestinal bleed by portal hypertension (4 days required for stable condition)
  • Active sepsis (4 days required for stable condition)
  • Patient currently treated by antibiotic
  • Concomitant Liver cancer (HCC) or extrahepatic malignancy
  • Type 1 hepatorenal syndrome (HRS) or renal failure defined as a serum creatinine >221 μmol/L (>2.5 mg/dL) or the requirement for renal replacement therapy
  • Grade 4 Hepatic Encephalopathy (HE) by West Haven criteria
  • Individuals dependent on inotropic (eg, epinephrine or norepinephrine) or ventilatory support (ie, endotracheal intubation or positive-pressure ventilation)
  • Disseminated intravascular coagulation
  • Intestinal paralysis
  • History of liver transplantation

Other general diseases or severe conditions:

  • HIV disease
  • Intestinal paralysis
  • Intestinal inflammatory disease (Crohn or Ulcerative colitis)
  • Clostridium difficilae infection
  • Clinical suspicion of pneumonia
  • Uncontrolled sepsis
  • Acute Alcoholic pancreatitis
  • Noncontrolled alcohol withdrawal syndrome
  • Cardiac or respiratory bad conditions

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: sAH patients
the recruitment of patients with sAH will be carried out from the Hepatogastroenterology Service of the University Hospital of Amiens.
Other: stool withdrawal
stool withdrawal at day 0 and day 7
Experimental: Alcohol controls without liver complications
the recruitment of alcohol controls will concern patients followed for alcohol addiction without sAH in the antecedents or evolutionary. It will be carried out by the Hospital of Roye-Montdidier. The total number of controls will be equivalent to the number of sAH patients, matched for age and sex.
Other: stool withdrawal
stool withdrawal at day 0 and day 7
Active Comparator: Healthy non-alcoholic witnesses
the general population will be called with a matching on age
Other: stool withdrawal
stool withdrawal at day 0 and day 7

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
variation of sample bacterial composition between the three groups
Time Frame: day 7
day 7

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Centre Hospitalier Universitaire, Amiens

Collaborators

CH Montdidier

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 15, 2023

Primary Completion (Estimated)

November 1, 2028

Study Completion (Estimated)

November 1, 2028

Study Registration Dates

First Submitted

November 21, 2023

First Submitted That Met QC Criteria

December 5, 2023

First Posted (Actual)

December 6, 2023

Study Record Updates

Last Update Posted (Actual)

December 6, 2023

Last Update Submitted That Met QC Criteria

December 5, 2023

Last Verified

December 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PI2023_843_0123

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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