Effect of Heavy Alcohol Consumption on Farnesoid X Receptor (FXR) Signaling

The main purpose of this study is to see whether heavy drinking will interfere with a specific pathway, called FXR signaling in the liver. The abnormality of this pathway may lead to liver injury in some patients who drink heavily.

Study Overview

• Status: Completed
• Conditions: Alcohol Consumption
• Intervention / Treatment: Drug: Placebo; Drug: 10 mg Obeticholic Acid (OCA)

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Not Applicable

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
      • Indiana University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Individuals ≥ 21 to 65 years old
• Able to provide informed consent & negative urine pregnancy test where appropriate
• Healthy controls must have not consumed any alcohol within 3 months prior to the screening visit
• Heavy alcohol drinking is 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
• Women of child bearing potential should be willing to practice contraception throughout the treatment period

Exclusion Criteria:

• Active infection as evidenced by positive urine culture, blood culture, or pneumonia
• Serum creatinine > 1.5 mg/dL
• Known co-existing infection with hepatitis C, hepatitis B, or HIV
• Significant systemic or major illness including COPD, CHF and renal failure that in the opinion of the Investigator would preclude the patient from participating in and completing the study.
• Participation in another investigational drug, biologic, or medical device trial within 30 days prior to Screening
• Previous history of jaundice or signs of liver diseases such as spider angiomata, ascites, or history of esophageal varices or hepatic encephalopathy
• Total bilirubin > 2 mg/dl and INR > 1.5 Page 20 of 37
• Women who are pregnant or nursing
• 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).
• Subjects who are taking warfarin

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Non-drinking Controls; Non-drinking healthy controls
Placebo Comparator: Placebo; Heavy Drinkers on placebo	Drug: Placebo; 1 tablet of placebo, taken orally daily with water, approximately 30 minutes prior to breakfast for 4 weeks.
Experimental: 10 mg Obeticholic Acid (OCA); 10 mg Obeticholic Acid (OCA) Study medication will be administered orally, once daily for 4 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 4 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in Bile Salt Metabolism (C4 )Levels to Determine Effect of FXR	Baseline to 28 days
Change in FGF19 Levels to Determine Effect of FXR	Baseline to 28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Fasting Serum Bile Salt Levels		Baseline to 28 days
Change in Oxidative Stress Level by Measuring Malondialdehyde		Baseline to 28 days
Change in CYP2E1 Activity by Measuring Chlorzoxazone Clearance		Baseline to 28 days
Change in Gut Permeability Through Lactulose/Mannitol Test	This is the measurement to quantify two non-metabolized sugar molecules-lactulose and mannitol-to determine the gut permeability	Baseline to 28 days
Change in Bacterial Translocation Through Measures of Plasma LPS		Baseline to 28 days
Change in Intestinal Inflammation by Measuring Stool Calprotectin		Baseline to 28 days
Change in Activation of Innate Immunity Through Measures of TNF-alpha		Baseline to 28 days
Change in Bacterial Translocation Through Measures of Serum sCD14		Baseline to 28 days
Change in Activation of Innate Immunity Through Measures of IL-6		Baseline to 28 days
Change in Activation of Innate Immunity Through Measures of IL-8		Baseline to 28 days
Change in Activation of Innate Immunity Through Measures of IL-1		Baseline to 28 days

Collaborators and Investigators

• Sponsor: Suthat Liangpunsakul
• Collaborators: National Institute on Alcohol Abuse and Alcoholism (NIAAA); Intercept Pharmaceuticals
• Investigators: Principal Investigator: Suthat Liangpunsakul, MD, Indiana University

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2016
• Primary Completion (Actual): September 1, 2019
• Study Completion (Actual): September 1, 2019

Study Registration Dates

• First Submitted: January 6, 2016
• First Submitted That Met QC Criteria: January 11, 2016
• First Posted (Estimate): January 13, 2016

Study Record Updates

• Last Update Posted (Actual): April 25, 2023
• Last Update Submitted That Met QC Criteria: April 3, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Drinking Behavior; Alcohol Drinking
• Other Study ID Numbers: TREAT 005