Clinical trial NCT02039219: Trial of Obeticholic Acid in Patients With Moderately Severe Alcoholic Hepatitis (AH)
Official title: A Double-Blind, Placebo-Controlled Trial of Obeticholic Acid in Patients With Moderately Severe Alcoholic Hepatitis (AH)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Alcoholic Hepatitis
Lead sponsor: Indiana University
Sponsor class: OTHER
Collaborators: name: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
name: Intercept Pharmaceuticals
First posted: 2014-01-17
Enrollment: 19
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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 \< 20
* 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

Primary outcomes:
measure: MELD Score Mean(SD)
timeFrame: Baseline to 6 weeks (Day 42)
measure: Incidence of Serious Adverse Events (SAEs) During the Treatment Phase
timeFrame: Baseline to 6 weeks (Day 42)
measure: MELD Score Change From Baseline Mean(SD)
timeFrame: Baseline to 6 weeks (Day 42)
Secondary outcomes:
measure: Any SAEs During the Follow-up Phase
timeFrame: Days 42 to 180
measure: SAEs Attributable to the Study Medicine During the Treatment and Follow-up Phases
timeFrame: Baseline to 180 days
measure: Adverse Events (AEs) During the Treatment and Follow-up Phases
timeFrame: Baseline to 180 days
measure: Change in MELD Score at 90 and 180 Days
timeFrame: Days 90 and 180
measure: Change in Child-Pugh Score at Day 42, 90 and 180 Days
timeFrame: Days 42, 90 and 180
measure: Percentage of Participants Deceased at Day 42, 90 and 180
timeFrame: Days 42, 90 and 180
measure: Rates of Hospitalization
timeFrame: Baseline to 180 days
measure: Changes in Intestinal Inflammation
timeFrame: Baseline to Day 180
measure: Changes in Serum Oxidative Stress.
timeFrame: Baseline to 180 days
measure: Length of Hospital Stays
timeFrame: Baseline to 180 days
measure: Changes in Bacterial Translocation
timeFrame: Baseline to 180 days
measure: Changes in Cytokines
timeFrame: Baseline to 180 days
measure: Changes in Activation of Innate Immunity
timeFrame: Baseline to 180 days
measure: Discontinuation Rate During the Treatment and Follow-up Phases
timeFrame: Baseline to 180 days
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Philadelphia
country: United States
facility: Einstein Healthcare Network
state: Pennsylvania
city: Richmond
country: United States
facility: Virgina Commonwealth University
state: Virginia
Study officials:
affiliation: Indiana University
name: Naga Chalasani, MD
role: PRINCIPAL_INVESTIGATOR
References: