Endotoxin Exposure to Examine the Role of Inflammation in Alcohol Use

April 28, 2026 updated by: Lara Ray, PhD, University of California, Los Angeles

Understanding the Role of Inflammation in Alcohol Use Disorder: An Inflammatory Challenge Using Lipopolysaccharide

The study design consists of a randomized, double-blind, placebo-controlled study of low dose endotoxin. Individuals with current AUD (n=32) and matched controls without AUD (n=32) will be randomly assigned to receive a single intravenous (I.V.) infusion of either low dose endotoxin (0.8 ng/kg of body weight) or placebo (same volume of 0.9% saline solution) to determine the acute and protracted role of inflammation in alcohol use.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Participants will be recruited from the community through campaigns in radio, buses, social media, and print publications. After a telephone interview, eligible individuals will complete in-person screening to assess for presence of DSM-5 alcohol use disorder and additional inclusion/exclusion criteria. Eligible participants will complete a physical exam to assess medical safety, including EKG and laboratory tests. Participants who pass the physical exam will then be randomized to an experimental condition (i.e., endotoxin vs. placebo). Randomization will be stratified by sex (male versus female) and AUD (moderate versus severe). Participants will complete an alcohol cue-exposure paradigm in the lab 2 hours post infusion, the time of peak cytokine response. Plasma levels of inflammatory cytokines (i.e., interleukin-6 (IL-6) and tumor necrosis factor-α (TNF- α)), mood, and alcohol craving, will be assessed at baseline and then hourly for six hours post infusion. Following the infusion, all participants will complete a 7-day follow-up phase consisting of daily diary surveys of mood, alcohol craving, and alcohol consumption. The adverse events will be managed by study nurse practitioners during the endotoxin challenge.

Study Type

Interventional

Enrollment (Estimated)

64

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria (AUD Group):

  1. Be between the ages of 21 and 65
  2. Meet current (i.e., past month) DSM-5 diagnostic criteria for moderate to severe AUD
  3. Be non-treatment seeking for AUD
  4. Report drinking at least 28 drinks per week if male (21 drinks per week if female) in the 28 days prior to consent.

  5. Must agree to one of the following methods of birth control (if female), unless she or partner are surgically sterile:

    • Oral contraceptives
    • Contraceptive sponge
    • Patch
    • Double barrier
    • Intrauterine contraceptive device
    • Etonogestrel implant
    • Medroxyprogesterone acetate contraceptive injection
    • Complete abstinence from sexual intercourse
    • Hormonal vaginal contraceptive ring

Inclusion Criteria (Control Group):

(1) The control group will be age-, sex-, smoking status-, and BMI-matched healthy individuals who drink at or below moderate drinking levels (≤1 drink/day for females, ≤2 drinks/day for males) and have no lifetime history of AUD.

Exclusion Criteria (All Groups):

  1. Have a current (last 12 months) DSM-5 diagnosis of substance use disorder for any psychoactive substances other than alcohol and nicotine
  2. Have a lifetime DSM-5 diagnosis of schizophrenia, bipolar disorder, or any psychotic disorder
  3. Have current moderate to severe depression as indicated by a score of ≥ 21 on the Beck Depression Inventory - II (BDI-II)
  4. Have current suicidal ideation or lifetime history of suicide attempt as reported on the Columbia-Suicide Severity Rating Scale (C-SSRS)
  5. Have a positive urine screen for drugs other than cannabis;
  6. Have clinically significant alcohol withdrawal symptoms as indicated by a score ≥ 10 on the Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-R)
  7. Have an intense fear of needles or have had any adverse reactions to needle puncture
  8. Be pregnant, nursing, or planning to become pregnant while taking part in the study
  9. Have a body mass index (BMI) greater than 30
  10. Have a medical condition that may interfere with safe study participation (e.g., unstable cardiac, renal, or liver disease, uncontrolled hypertension or diabetes, autoimmune or inflammatory disease)
  11. Have clinically significant abnormal EKG
  12. Have > Grade 2 laboratory abnormalities, based on FDA Guidance Document "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials"
  13. Have any other circumstances that, in the opinion of the investigators, compromises participant safety

  14. To participate in the inflammatory challenge, participants must not show any of the following upon arrival to the inflammatory challenge study visit:

    1. BrAC > 0.000 g/dl
    2. clinical withdrawal (CIWA-R) score ≥ 10
    3. blood pressure ≤ 90/60 or ≥ 160/120
    4. resting pulse ≤ 50 beats/minute or > 100 beats/minute
    5. temperature ≥ 99.5°F
    6. recent (past 2 weeks) acute illness or vaccination
    7. score of 10+ on Physical Sickness Symptoms Assessment

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Endotoxin
Individuals with alcohol use disorder vs. control who receive a bolus dose of endotoxin (0.8 ng/kg of body weight).
Drug: Endotoxin
Bolus dose of 0.8 ng/kg
Other Names:
  • Lipopolysaccharide
Placebo Comparator: Placebo
Individuals with alcohol use disorder vs. control matched to endotoxin at same volume of 0.9% saline solution.
Other: Placebo saline
Matched to endotoxin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Acute Phase: To determine the effect of acute inflammation on mood in AUD versus controls.
Time Frame: Mood will be collected at baseline (prior to infusion) and hourly for 6 hours post-infusion.
The Profile of Mood States (POMS) is a self-report questionnaire that measures dimensions of mood. Four items from the POMS were summed to calculate the negative mood subscale. The items included "discouraged," downhearted," "uneasy," and "anxious." Participants rated the extent that they felt items "right now" on a scale from 0-4, with higher scores indicating more endorsement of the items. Items were summed to calculate negative mood subscale with the score ranging from 0-16, with higher scores indicating higher negative mood. The investigators were interested in whether low dose endotoxin would increase negative mood as compared to placebo in AUD vs control.
Mood will be collected at baseline (prior to infusion) and hourly for 6 hours post-infusion.
Acute Phase: To determine the effect of acute inflammation on cue-reactivity in AUD versus controls.
Time Frame: The cue-reactivity paradigm is conducted at baseline and at 2 hours post-infusion during the experimental visit.
Alcohol Urge Questionnaire (AUQ) score is the primary outcome for the cue-reactivity paradigm. The AUQ is comprised of eight items rated on a 7-point Likert scale with items related to the subjective experience of alcohol craving. The minimum value is 8 and the maximum value is 56 with a higher score indicating greater subjective alcohol craving. Phasic craving for alcohol following alcohol cue exposure was assessed using the first and last items from the AUQ during an alcohol cue reactivity paradigm at baseline and at time of expected peak cytokine response (T2). This subscale of 2 items about desire to drink rated on a 7-point Likert scale provided a minimum possible value of 2 and a maximum value of 14, with higher values indicating a higher craving to drink alcohol. The investigators are primarily interested in whether low dose endotoxin increases cue-induced craving for alcohol relative to placebo in AUD vs control.
The cue-reactivity paradigm is conducted at baseline and at 2 hours post-infusion during the experimental visit.
Acute Phase: To determine the effect of acute inflammation on biomarkers in AUD versus controls.
Time Frame: Blood samples will be collected at baseline (prior to infusion) and hourly for 6 hours post-infusion.
Plasma levels of inflammatory cytokines Interleukin-6 (IL-6), IL-8, and tumor necrosis factor-α (TNF- α) will be collected at baseline and hourly timepoints post-infusion for 6 hours. The investigators are primarily interested in whether low dose endotoxin increases peripheral cytokines relative to placebo in AUD vs control.
Blood samples will be collected at baseline (prior to infusion) and hourly for 6 hours post-infusion.
Follow-up Phase: To determine the protracted effects of acute inflammation on self-reported craving and alcohol use in AUD versus controls.
Time Frame: 7-day follow-up phase after acute infusion visit.
Individuals will complete a 7-day follow-up after the infusion visit consisting of daily diary online questionnaires to assess protracted endotoxin-induced effects on alcohol craving (Alcohol Urge Questionnaire (AUQ)) and alcohol consumption.
7-day follow-up phase after acute infusion visit.
Follow-up Phase: To determine the protracted effects of acute inflammation on mood in AUD versus controls.
Time Frame: 7-day follow-up phase after acute infusion visit.
Individuals will complete a 7-day follow-up after the infusion visit consisting of daily diary online questionnaires to assess protracted endotoxin-induced effects on mood symptoms (Profile of Mood States).
7-day follow-up phase after acute infusion visit.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of California, Los Angeles

Collaborators

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Investigators

  • Principal Investigator: Lara Ray, PhD, University of California, Los Angeles

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

June 1, 2026

Primary Completion (Estimated)

June 1, 2028

Study Completion (Estimated)

July 1, 2028

Study Registration Dates

First Submitted

February 27, 2026

First Submitted That Met QC Criteria

February 27, 2026

First Posted (Actual)

March 5, 2026

Study Record Updates

Last Update Posted (Actual)

May 4, 2026

Last Update Submitted That Met QC Criteria

April 28, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 25-1738
  • 2K24AA025704-06 (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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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