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

Alcohol Consumption Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02654236
• Other study ID #: TREAT 005
• Status: Completed
• Phase: N/A
• Start date: April 2016
• Est. completion date: September 2019

Study information

• Verified date: April 2023
• Source: Indiana University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: September 2019
• Est. primary completion date: September 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 21 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Alcohol Consumption
• Alcohol Drinking

Intervention

Drug:
• Placebo
1 tablet of placebo, taken orally daily with water, approximately 30 minutes prior to breakfast for 4 weeks.
• 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.

Locations

Country	Name	City	State
United States	Indiana University	Indianapolis	Indiana

Sponsors (3)

Lead Sponsor	Collaborator
Suthat Liangpunsakul	Intercept Pharmaceuticals, National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Bile Salt Metabolism (C4 )Levels to Determine Effect of FXR		Baseline to 28 days
Primary	Change in FGF19 Levels to Determine Effect of FXR		Baseline to 28 days
Secondary	Change in Fasting Serum Bile Salt Levels		Baseline to 28 days
Secondary	Change in Oxidative Stress Level by Measuring Malondialdehyde		Baseline to 28 days
Secondary	Change in CYP2E1 Activity by Measuring Chlorzoxazone Clearance		Baseline to 28 days
Secondary	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
Secondary	Change in Bacterial Translocation Through Measures of Plasma LPS		Baseline to 28 days
Secondary	Change in Intestinal Inflammation by Measuring Stool Calprotectin		Baseline to 28 days
Secondary	Change in Activation of Innate Immunity Through Measures of TNF-alpha		Baseline to 28 days
Secondary	Change in Bacterial Translocation Through Measures of Serum sCD14		Baseline to 28 days
Secondary	Change in Activation of Innate Immunity Through Measures of IL-6		Baseline to 28 days
Secondary	Change in Activation of Innate Immunity Through Measures of IL-8		Baseline to 28 days
Secondary	Change in Activation of Innate Immunity Through Measures of IL-1		Baseline to 28 days