Endotoxin Exposure to Examine the Role of Inflammation in Alcohol Use

NCT07452146 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 25-17382K24AA025704-06
• Study Type: interventional
• Target: 64
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Alcohol Use Disorder; Inflammatory Response; Craving

Keywords

Endotoxin

Outcome Measures

Primary Outcomes (5)

• Acute Phase: To determine the effect of acute inflammation on mood in AUD versus controls.

  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.

  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.

  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.

  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.

  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.

Study Arms (2)

Endotoxin

EXPERIMENTAL

Individuals with alcohol use disorder vs. control who receive a bolus dose of endotoxin (0.8 ng/kg of body weight).

Drug: Endotoxin

Placebo

PLACEBO COMPARATOR

Individuals with alcohol use disorder vs. control matched to endotoxin at same volume of 0.9% saline solution.

Other: Placebo saline

Interventions

Endotoxin DRUG

Bolus dose of 0.8 ng/kg

Also known as: Lipopolysaccharide

Endotoxin

Placebo saline OTHER

Matched to endotoxin

Placebo

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Have a current (last 12 months) DSM-5 diagnosis of substance use disorder for any psychoactive substances other than alcohol and nicotine
• Have a lifetime DSM-5 diagnosis of schizophrenia, bipolar disorder, or any psychotic disorder
• Have current moderate to severe depression as indicated by a score of ≥ 21 on the Beck Depression Inventory - II (BDI-II)
• Have current suicidal ideation or lifetime history of suicide attempt as reported on the Columbia-Suicide Severity Rating Scale (C-SSRS)
• Have a positive urine screen for drugs other than cannabis;
• Have clinically significant alcohol withdrawal symptoms as indicated by a score ≥ 10 on the Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-R)
• Have an intense fear of needles or have had any adverse reactions to needle puncture
• Be pregnant, nursing, or planning to become pregnant while taking part in the study
• Have a body mass index (BMI) greater than 30
• 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)
• Have clinically significant abnormal EKG
• 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"
• Have any other circumstances that, in the opinion of the investigators, compromises participant safety
• To participate in the inflammatory challenge, participants must not show any of the following upon arrival to the inflammatory challenge study visit:
• BrAC \> 0.000 g/dl

Sponsors & Collaborators

• University of California, Los Angeles: lead
• National Institute on Alcohol Abuse and Alcoholism (NIAAA): collaborator

MeSH Terms

Conditions

Alcoholism

Interventions

Endotoxins; Lipopolysaccharides

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Bacterial Toxins; Toxins, Biological; Biological Factors; Glycoconjugates; Carbohydrates; Polysaccharides, Bacterial; Polysaccharides; Lipids; Antigens, Bacterial; Antigens

Study Officials

• Lara Ray, PhD

  University of California, Los Angeles

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lara Ray, PhD

CONTACT

(310) 794-5383; lararay@psych.ucla.edu

Jessica Jenkins, MS

CONTACT

310-206-6756; jenkinsj@ucla.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: The study investigator, medical personnel, and participants will be blind to drug condition.
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Randomized, triple-blind, placebo-controlled, parallel-group study of low dose endotoxin (0.8 ng/kg)

Study Record Dates

• First Submitted: February 27, 2026
• First Posted: March 5, 2026
• Study Start: June 1, 2026
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): July 1, 2028
• Last Updated: May 4, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share