Alcoholic Hepatitis Network Observational Study

The purpose of this research study is to create a clinical database and bio-repository. To do this, we will obtain blood, urine, saliva, and stool samples (e.g., biological samples) and personal health information from you to use in future research studies related to alcoholic hepatitis or other diseases. Part of your blood sample will be used to extract your DNA. DNA is the genetic material that gives us unique characteristics. We are doing this research study because we are trying to find out more about how and why illnesses related to alcoholic hepatitis or other diseases occur in people. To do this, we will study the biological samples and personal health information from healthy and sick people.

A "biological sample" is usually blood, but can be any body fluid. "Personal Health Information" includes such items as your name, age, gender, race, and/or your medical information. It can also include data from measurements and tests that you had while participating in another research study or that were done during the course of your regular medical care or doctor visits.

Study Overview

• Status: Recruiting
• Conditions: Alcoholic Hepatitis

Detailed Description

What should I know about this research?

• Someone will explain this research to you.
• Taking part in this research is voluntary. Whether you take part is up to you.
• If you don't take part, it won't be held against you.
• You can take part now and later drop out, and it won't be held against you
• If you don't understand, ask questions.
• Ask all the questions you want before you decide.

How long will I be in this research? We expect that your taking part in this research will last up to 6 months, after the 6 months we will look in your medical records every 180 days for up to five years.

Why is this research being done? The purpose of this research is to create a clinical database and bio-repository to study alcoholic hepatitis.

What happens to me if I agree to take part in this research? If you decide to take part in this research study, the general procedures include: 1) allowing the investigators to review your medical records, 2) answering questions about you and your health, 3) completing questionnaires about alcohol use, 4) having a physical exam and blood drawn, and 5) providing urine and stool samples.

Could being in this research hurt me? The most important risks or discomforts that you may expect from taking part in this research include mild pain from blood draws and a small chance for a loss of confidentiality (e.g., unauthorized users gain access to sensitive and protected data about you).

Will being in this research benefit me? It is not expected that you will personally benefit from this research. Possible benefits to others may include understanding specific health conditions in patients with alcoholic hepatitis or other diseases.

• Study Type: Observational
• Enrollment (Estimated): 1260

Contacts and Locations

• Study Contact: Name: Savannah Yarnelle; Phone Number: 317-278-6424; Email: samussel@iu.edu

Study Locations

• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46202-2879
      • Recruiting
      • IU School of Medicine
      • Contact: Lauren Nephew, MD; Phone Number: 317-278-0414; Email: lnephew@iu.edu
      • Principal Investigator: Lauren Nephew, MD
  • Kentucky
    • Louisville, Kentucky, United States, 40292
      • Recruiting
      • University of Louisville
      • Sub-Investigator: Steve Mahanes
      • Principal Investigator: Craig McClain
      • Contact: Suman Jha; Email: sumankumar.jha@louisville.edu
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Beth Israel Deaconess Medical Center
      • Contact: Hannah Siegenberg; Email: hsiegenb@bidmc.harvard.edu
      • Principal Investigator: Gyongyi Szabo, MD
    • Worcester, Massachusetts, United States, 01655
      • Terminated
      • University of Massachusetts
  • Minnesota
    • Rochester, Minnesota, United States, 55901
      • Recruiting
      • Mayo Clinic
      • Contact: Amy Olofson, BSN; Phone Number: 507-284-4531; Email: olofson.amy@mayo.edu
      • Principal Investigator: Vijay Shah, MD
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Recruiting
      • Cleveland Clinic
      • Contact: Sugapradha Saravanan; Phone Number: 216-445-0688; Email: SARAVAS2@ccf.org
      • Principal Investigator: Srinivasan Dasarathy, MD
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15260
      • Terminated
      • University of Pittsburgh
  • Texas
    • Dallas, Texas, United States, 75390
      • Recruiting
      • University of Texas Southwestern Medical School
      • Contact: Leticia Rodriguez; Phone Number: 214-648-3352; Email: Leticia.Rodriguez@utsouthwestern.edu
      • Principal Investigator: Mack Mitchell, MD
  • Virginia
    • Richmond, Virginia, United States, 23284
      • Recruiting
      • Virginia Commonwealth University
      • Principal Investigator: Arun Sanyal, MD
      • Contact: Arun Sanyal; Phone Number: 804-828-4030; Email: arun.sanyal@vcuhealth.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

Any subject with Alcoholic hepatitis, Heavy healthy drinkers, and Healthy controls

Description

CASES: Heavy drinkers with alcoholic hepatitis

Inclusion criteria

1. A clinical diagnosis of alcoholic hepatitis as defined by the NIAAA pan-consortia for AH:

   1. Onset of jaundice (defined as serum total bilirubin >3 mg/dL) within the prior 8 weeks to screening visit
   2. Regular consumption of alcohol with an intake of > 40 gm daily or >280gm weekly on average for women and > 60 gm daily or >420gm weekly on average for men for 6 months or more, with less than 8 weeks of abstinence before onset of jaundice
   3. AST > 50 IU/l
   4. AST:ALT > 1.5 and both values < 400 IU/l
   5. and/or histological evidence of AH*
2. Serum total bilirubin >3 mg/dL
3. Subject or guardian ability to understand and willingness to provide written consent
4. Age greater or equal to 21 years
5. Re-enrolment of an alcoholic hepatitis donor is permissible up to 4 times if the donor presents with a new episode of alcoholic hepatitis 24 weeks or longer after the most recent enrolment in the study

Exclusion criteria

1. Liver disease significantly caused by hemochromatosis, autoimmune liver disease, Wilson disease, and acute viral hepatitis (NOTE: The presence of chronic hepatitis C, hepatitis B, HIV, or stage 1 (one lesion <2 cm) HCC is not exclusion to participation)
2. Pregnant or breast feeding
3. Received liver transplant
4. Based on the judgment of the investigator, subject is not capable of understanding or complying with the study requirements

CONTROLS: Heavy drinkers without significant liver disease Inclusion criteria

1. History of chronic alcohol consumption sufficient to cause liver damage. Generally, this is considered to be >40 g/day or >280g/week on average for women and >60 g/day or >420 g/week on average for men, for 6 months or more. Judgement about chronic alcohol consumption will be made by the site investigator.
2. Subject or guardian ability to understand and willingness to provide written consent
3. Age greater or equal to 21 years

Exclusion criteria

1. Past evidence of alcoholic liver disease, defined as a bilirubin > 2.0 mg/dL, an AST > 1.5 ULN, and any hospital admission for liver disease, or the presence of esophageal varices or ascites (at any time in the past)

2. Liver disease significantly caused by hemochromatosis, autoimmune liver disease, Wilson disease, NAFLD, and acute viral hepatitis (NOTE: The presence of chronic hepatitis C, hepatitis B, or HIV is not exclusion to participation.)

   *Individuals with a diagnosis of Gilbert's can have total bilirubin up to 3.0 mg/dL and still be eligible for participation.

3. Alcohol intake at less than 40 g/day or 280g/week on average for women and 60 g/day or 420 g/week on average for men for longer than the past 28 days
4. If liver stiffness has been assessed within the prior 90 days, then stiffness suggesting fibrosis of F1 or greater is excluded. For Fibroscan, this is a fibrosis score >7.0 kPa.
5. Received liver transplant
6. Pregnant or breast feeding

7. Any of the following laboratory abnormalities within 90 days prior to signing the consent.

   1. Total bilirubin: >ULN*
   2. INR: > 1.4

Healthy Controls

Inclusion criteria

1. AUDIT-C scores of <4 for men and <3 for women (signifying no alcohol misuse)
2. Abstinent (consumption of less than one standard drink/week) during the 6 months prior to enrolment
3. Ability to understand and willingness to provide written consent.
4. Age greater or equal to 21 years

Exclusion criteria

1. Clinical history or laboratory evidence of liver disease including alcoholic liver disease, NAFLD, hemochromatosis, alcoholic hepatitis, autoimmune liver disease, Wilson disease, hepatitis C, or hepatitis B.
2. Presence of diabetes (requiring treatment with oral agents or insulin).
3. Significant heart disease (prior history of heart disease, other than hypertension)
4. Chronic lung disease (requiring chronic treatment)
5. Immune related conditions (such as Crohn's disease, rheumatoid arthritis, ulcerative colitis, systemic lupus erythematosus, severe psoriasis, etc.)
6. Known infection with HIV
7. Presumed infection, or use of antibiotics or other medications (e.g., corticosteroids) that would affect immune function, within the past 14 days
8. BMI>35
9. Current or known history of cancer (except in situ carcinoma of the cervix or adequately treated basal or squamous cell carcinoma of the skin) within 5 years prior to enrollment
10. Received liver transplant
11. Pregnant or breast feeding

12. Any of the following laboratory abnormalities within 90 days prior to signing the consent.

    1. Hemoglobin: <10 g/dL
    2. Conjugated bilirubin: > ULN
    3. INR: > 1.4
    4. AST: >40 IU/mL
    5. ALT: >40 IU/mL
13. Based on the judgment of the investigator, subject is not capable of complying with the study requirements

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Cases; Heavy drinkers with alcoholic hepatitis
Controls; Heavy drinkers without significant liver disease
Donor; Healthy non-drinkers

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To collect and store clinical data to facilitate investigations of the epidemiology, diagnosis, pathophysiology, natural history, and treatment of alcoholic hepatitis.	5 years

Secondary Outcome Measures

Outcome Measure	Time Frame
To develop a bio-specimen bank comprised of plasma, serum, PBMC, saliva, DNA, urine, stool, liver biopsy and other biological specimens obtained from patients with alcoholic hepatitis, heavy drinkers without clinical liver disease, and healthy subjects.	5 years

Collaborators and Investigators

• Sponsor: Indiana University
• Collaborators: National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Study record dates

Study Major Dates

• Study Start (Actual): April 17, 2019
• Primary Completion (Estimated): August 1, 2024
• Study Completion (Estimated): August 1, 2024

Study Registration Dates

• First Submitted: February 20, 2019
• First Submitted That Met QC Criteria: February 20, 2019
• First Posted (Actual): February 22, 2019

Study Record Updates

• Last Update Posted (Actual): February 20, 2024
• Last Update Submitted That Met QC Criteria: February 16, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Digestive System Diseases; Alcohol-Related Disorders; Substance-Related Disorders; RNA Virus Infections; Virus Diseases; Infections; Liver Diseases; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Liver Diseases, Alcoholic; Alcohol-Induced Disorders; Hepatitis; Hepatitis A; Hepatitis, Alcoholic
• Other Study ID Numbers: AlcHepNet-01

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