Trial of Obeticholic Acid in Patients With Moderately Severe Alcoholic Hepatitis (AH) (TREAT)

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified June 2014 by Indiana University
Sponsor:
Collaborators:
Intercept Pharmaceuticals
Information provided by (Responsible Party):
Indiana University
ClinicalTrials.gov Identifier:
NCT02039219
First received: January 15, 2014
Last updated: June 4, 2014
Last verified: June 2014
  Purpose

The main purpose of this study is to test the effectiveness of Obeticholic Acid when used in patients with moderately severe alcoholic hepatitis. The researchers suspect that individuals with alcoholic hepatitis have certain abnormalities in how their body handles bile acids (a product made by the liver on a daily basis) produced by the liver. Obeticholic acid has been shown to affect bile acid abnormalities and thus it is possible that obeticholic acid may improve liver condition in individuals with alcoholic hepatitis.


Condition Intervention Phase
Alcoholic Hepatitis
Drug: Placebo
Drug: 10 mg Obeticholic Acid (OCA)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Double-Blind, Placebo-Controlled Trial of Obeticholic Acid in Patients With Moderately Severe Alcoholic Hepatitis (AH)

Resource links provided by NLM:


Further study details as provided by Indiana University:

Primary Outcome Measures:
  • Change in MELD score at 6 weeks [ Time Frame: baseline to 6 weeks ] [ Designated as safety issue: No ]
  • Incidence of serious adverse events (SAEs) during the treatment phase [ Time Frame: baseline to 6 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Any SAEs during the follow-up phase [ Time Frame: Days 42 to 180 ] [ Designated as safety issue: Yes ]
  • SAEs attributable to the study medicine during the treatment and follow-up phases [ Time Frame: Days 42 to 180 ] [ Designated as safety issue: Yes ]
  • Adverse events (AEs) and discontinuation rates during the treatment and follow-up phases [ Time Frame: days 42 to 180 ] [ Designated as safety issue: Yes ]
  • Change in MELD score at 90 and 180 days [ Time Frame: day 90 and 180 ] [ Designated as safety issue: No ]
  • Change in Child-Pugh score at 6 weeks and at 90 and 180 days [ Time Frame: Day 90 and 180 ] [ Designated as safety issue: No ]
  • Mortality rate at Week 6 and at 90 and 180 days [ Time Frame: Week 6 and Days 90 and 180 ] [ Designated as safety issue: No ]
  • Rates of hospitalization [ Time Frame: baseline to day 180 ] [ Designated as safety issue: No ]
  • Changes in intestinal permeability [ Time Frame: baseline to day 180 ] [ Designated as safety issue: No ]
  • Changes in intestinal inflammation [ Time Frame: baseline to day 180 ] [ Designated as safety issue: No ]
  • Changes in hepatic CYP2E1 activity [ Time Frame: baseline to day 180 ] [ Designated as safety issue: No ]
  • Changes in serum oxidative stress. [ Time Frame: baseline to day 180 ] [ Designated as safety issue: No ]
  • Length of hospital stays [ Time Frame: Baseline to 180 days ] [ Designated as safety issue: No ]
  • Changes in bacterial translocation [ Time Frame: baseline to 180 days ] [ Designated as safety issue: No ]
  • Changes in cytokines [ Time Frame: baseline to 180 days ] [ Designated as safety issue: No ]
  • Changes in activation of innate immunity [ Time Frame: baseline to 180 days ] [ Designated as safety issue: No ]

Estimated Enrollment: 60
Study Start Date: June 2014
Estimated Study Completion Date: December 2018
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Placebo
Drug: Placebo
1 tablet of placebo, taken orally daily with water, approximately 30 minutes prior to breakfast for 6 weeks.
Experimental: 10 mg Obeticholic Acid (OCA)
10 mg Obeticholic Acid (OCA) Study medication will be administered orally, once daily for 6 weeks.
Drug: 10 mg Obeticholic Acid (OCA)
10 mg Obeticholic Acid (OCA) Study medication will be administered orally, once daily, approximately 30 minutes prior to breakfast for 6 weeks.
Other Name: INT-747

  Eligibility

Ages Eligible for Study:   21 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Individuals ≥ 21 years with a diagnosis of acute AH. The diagnosis of acute alcoholic hepatitis will be based on clinical features and testing including hepatomegaly, jaundice, fever, leukocytosis, compatible liver biochemistries in the context of heavy alcohol consumption. A liver biopsy is not mandatory, but will be required to confirm the diagnosis if a firm diagnosis of AH cannot be made on clinical and laboratory criteria
  • Moderate severity defined as MELD score > 11 and < 19
  • Heavy alcohol consumption (defined as > 40 grams per day on average in women and > 60 grams per day on average in men for a minimum of 6 months and within the 6 weeks prior to study enrollment)
  • Written informed consent
  • Negative urine pregnancy test where appropriate
  • Women of child bearing potential should be willing to practice contraception throughout the treatment period

Exclusion Criteria:

  • Significant active infection (e.g., sepsis, or spontaneous bacterial peritonitis; SBP). Subjects can be reconsidered after the infection is under control.
  • Serum creatinine > 2.5 mg/dL
  • Must not be receiving systemic steroids > 1 week at the time of Screening or any experimental medicines for AH
  • Presence of any other disease or condition that is interfering with the absorption, distribution, metabolism, or excretion of drugs including bile salt metabolism in the intestine. Patients who have undergone gastric bypass procedures will be excluded (gastric lap band is acceptable).
  • Participation in another investigational drug, biologic, or medical device trial within 30 days prior to screening
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02039219

Contacts
Contact: Angela Howell, RN 3172789296 anmhowel@iu.edu
Contact: Megan Comerford, BS 3172789226 mcomerfo@iu.edu

Locations
United States, Indiana
Indiana University Not yet recruiting
Indianapolis, Indiana, United States, 46202
Contact: Angela Howell, RN    317-278-9296    anmhowel@iu.edu   
Contact: Megan Comerford, BS    3172789226    mcomerfo@iu.edu   
Principal Investigator: Naga Chalasani, MD         
Sub-Investigator: Suthat Liangpunsakul, MD         
Sub-Investigator: David Crabb, MD         
United States, Minnesota
Mayo Clinic Not yet recruiting
Rochester, Minnesota, United States, 55905
Contact: Sarah Wilder, RN, BSN    507-284-2698    wilder.sarah@mayo.edu   
Principal Investigator: Vijay Shah, MD         
United States, Virginia
Virgina Commonwealth University Not yet recruiting
Richmond, Virginia, United States, 23298
Contact: Susan Walker, RN, MSN    804-628-4395    walkersa@vcu.edu   
Principal Investigator: Arun J Sanyal, MD         
Sponsors and Collaborators
Indiana University
Intercept Pharmaceuticals
Investigators
Principal Investigator: Naga Chalasani, MD Indiana University
  More Information

Additional Information:
No publications provided

Responsible Party: Indiana University
ClinicalTrials.gov Identifier: NCT02039219     History of Changes
Other Study ID Numbers: TREAT 002, 1U01AA021840-01, U01AA021883, U01AA021891, U01AA021788
Study First Received: January 15, 2014
Last Updated: June 4, 2014
Health Authority: United States: Food and Drug Administration
United States: Data and Safety Monitoring Board
United States: Institutional Review Board

Additional relevant MeSH terms:
Hepatitis, Alcoholic
Hepatitis
Hepatitis A
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Liver Diseases, Alcoholic
Alcohol-Induced Disorders
Alcohol-Related Disorders
Substance-Related Disorders
Chemically-Induced Disorders

ClinicalTrials.gov processed this record on September 18, 2014