Effect of Endotoxin on Alcohol Consumption

Does Endotoxin Administration Increase Alcohol Consumption in Individuals With AUD?

For this protocol, the investigators plan to collect pilot data to examine the effect of endotoxin on drinking behavior in the human laboratory.

Study Overview

• Status: Completed
• Conditions: Alcohol Use Disorder
• Intervention / Treatment: Drug: Endotoxin

Detailed Description

This pilot study is a double-blind, placebo-controlled design, which will compare endotoxin (0.4ng/kg i.v.) to placebo (0.0ng/kg) in non-treatment seeking adults meeting criteria for DSM-5 alcohol use disorders (n=32 total, n=16 per group).

Eligibility screening consists of an intake session and a physical exam. Participants meeting eligibility criteria will be randomized to receive a single dose of 0.4ng/kg i.v. endotoxin or placebo during a single laboratory session to evaluate ad-libitum alcohol consumption.

During the laboratory session, endotoxin (or placebo) administration will precede a 2-hour alcohol self-administration period.

Participants will be scheduled for a follow-up appointment to evaluate drinking behavior.

Adverse events are evaluated during the laboratory session and follow-up, and will be tabulated.

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Yale School of Medicine

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age 21-65;
2. Able to read and write English;
3. Meets DSM-5 criteria for current (past 6 months) alcohol use disorder;
4. Drinking criteria: Males - Drinks > 14 drinks per week and exceeds 4 drinks per day at least twice per week; Females -Drinks > 7 drinks per week and exceeds 3 drinks per day at least twice per week.
5. Must meet drinking criteria during a consecutive 30-day period within the 90 days prior to baseline;
6. Laboratory sessions will be scheduled such that subjects will not have major responsibilities on the following day which might limit drinking during the self-administration session (e.g., job interview, exam).
7. Negative urine pregnancy test for women.

Exclusion Criteria:

1. Participants with any significant current medical conditions (neurological, cardiovascular [including hypertension or hypotension: sitting BP >160/100 or <90/60mmHg at baseline screening], endocrine, thyroid, renal, liver), seizures, delirium or hallucinations, or other unstable medical conditions including HIV;
2. Current DSM-5 substance use disorders, other than alcohol or nicotine;
3. A positive test result at intake appointment on urine drug screens conducted for illicit drugs, excluding cannabis;
4. Past 30 day use of psychoactive drugs including anxiolytics and antidepressants;
5. Women who are pregnant or nursing, or fail to use one of the following methods of birth control unless she or partner is surgically sterile or she is postmenopausal (hormone contraceptives [oral, implant, injection, patch, or ring], contraceptive sponge, double barrier [diaphragm or condom plus spermicide], or IUD);
6. Suicidal, homicidal or evidence of current (past 6-month) severe mental illness such as schizophrenia, bipolar disorder or major depression, or anxiety disorders;
7. Subjects treatment-seeking or who are currently in treatment for alcohol use;
8. Subjects with medical conditions contraindicating alcohol use (e.g., liver enzymes ≥3× normal);
9. Subjects likely to exhibit clinically significant alcohol withdrawal during the study. We will exclude subjects who a) have a history of perceptual distortions, seizures, delirium, or hallucinations upon withdrawal, or b) have a score of > 8 on the Clinical Institute Withdrawal Assessment scale at intake appointments;
10. Participation within the past 8 weeks in other studies that involve additive blood sampling and/or interventional measures that would be considered excessive in combination with the current application.
11. Subjects >38 on the Alcohol Use Disorders Identification Test (AUDIT)
12. Subjects with resting pulse >100 at challenge
13. Subjects with recent (past 2 weeks) acute illness or vaccination
14. Subjects with >Grade 2 laboratory abnormalities on screening

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Endotoxin; Endotoxin (0.4ng/kg i.v.) will be administered one time during the laboratory session.	Drug: Endotoxin; Endotoxin 0.4ng/kg i.v.; Other Names: Lipopolysaccharide
Placebo Comparator: Placebo; Administered one time during the laboratory session.	Drug: Endotoxin; Endotoxin 0.4ng/kg i.v.; Other Names: Lipopolysaccharide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Alcohol Consumption	Mean mls of alcohol consumed for endotoxin and placebo groups during 120 minute alcohol self-administration session.	120 minutes

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
• Investigators: Principal Investigator: Terril Verplaetse, PhD, Yale University

Study record dates

Study Major Dates

• Study Start (Actual): February 27, 2022
• Primary Completion (Actual): October 31, 2024
• Study Completion (Actual): October 31, 2024

Study Registration Dates

• First Submitted: August 21, 2020
• First Submitted That Met QC Criteria: August 21, 2020
• First Posted (Actual): August 26, 2020

Study Record Updates

• Last Update Posted (Estimated): November 3, 2025
• Last Update Submitted That Met QC Criteria: October 8, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Alcohol-Related Disorders; Alcoholism; Lipids; Biological Factors; Carbohydrates; Polysaccharides; Glycoconjugates; Bacterial Toxins; Toxins, Biological; Antigens; Antigens, Bacterial; Polysaccharides, Bacterial; Endotoxins; Lipopolysaccharides
• Other Study ID Numbers: 2000028772; 1R03AA028361-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No