Clinical trial NCT02654236: Effect of Heavy Alcohol Consumption on Farnesoid X Receptor (FXR) Signaling
Official title: Effect of Heavy Alcohol Consumption on Farnesoid X Receptor (FXR) Signaling
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Alcohol Consumption
Lead sponsor: Indiana University
Sponsor class: OTHER
Collaborators: name: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
name: Intercept Pharmaceuticals
First posted: 2016-01-13
Enrollment: 30
Sex: ALL
Minimum age (years): 21
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Change in Bile Salt Metabolism (C4 )Levels to Determine Effect of FXR
timeFrame: Baseline to 28 days
measure: Change in FGF19 Levels to Determine Effect of FXR
timeFrame: Baseline to 28 days
Secondary outcomes:
measure: Change in Fasting Serum Bile Salt Levels
timeFrame: Baseline to 28 days
measure: Change in Oxidative Stress Level by Measuring Malondialdehyde
timeFrame: Baseline to 28 days
measure: Change in CYP2E1 Activity by Measuring Chlorzoxazone Clearance
timeFrame: Baseline to 28 days
measure: Change in Gut Permeability Through Lactulose/Mannitol Test
timeFrame: Baseline to 28 days
measure: Change in Bacterial Translocation Through Measures of Plasma LPS
timeFrame: Baseline to 28 days
measure: Change in Intestinal Inflammation by Measuring Stool Calprotectin
timeFrame: Baseline to 28 days
measure: Change in Activation of Innate Immunity Through Measures of TNF-alpha
timeFrame: Baseline to 28 days
measure: Change in Bacterial Translocation Through Measures of Serum sCD14
timeFrame: Baseline to 28 days
measure: Change in Activation of Innate Immunity Through Measures of IL-6
timeFrame: Baseline to 28 days
measure: Change in Activation of Innate Immunity Through Measures of IL-8
timeFrame: Baseline to 28 days
measure: Change in Activation of Innate Immunity Through Measures of IL-1
timeFrame: Baseline to 28 days
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
Study officials:
affiliation: Indiana University
name: Suthat Liangpunsakul, MD
role: PRINCIPAL_INVESTIGATOR
References: