Phase 2
N=20
An Inflammatory Challenge Using Endotoxin
Alcohol Use Disorder · Inflammatory Response · Craving · Depressed Mood
Bottom Line
View on ClinicalTrials.gov: NCT04310423 ↗Enrolled (actual)
20
Serious AEs
0.0%
Results posted
May 2025
Primary outcome: Primary: Cue-induced Craving — 4.5004; 7.9081; 4.5004; 5.6178 score on a scale — p=0.036
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Placebo (Drug); Endotoxin (Biological)
- Age
- Adult · 21+ yrs
- Sex
- All
- Sponsor
- University of California, Los Angeles
- Primary completion
- Nov 2023
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Cue-induced Craving |
4.5004; 7.9081; 4.5004; 5.6178 | 0.036 sig |
| PRIMARY Change in Negative Mood |
0.60; 0.80; 0.50; 0.90; 0.50; 0.90 | >0.05 |
| SECONDARY Change in Reward Responsiveness |
1.46; 1.29; 1.98; 1.27; -0.07; 0.16 | >0.05 |
| SECONDARY Change in Reward Responsiveness |
1.46; 1.29; 1.98; 1.27; -0.07; 0.16 | >0.05 |
| SECONDARY Effect on Neural Alcohol Cue-reactivity |
3190; 1942; 931; 920; 518 | <0.001 sig |
Summary
The study design consists of a randomized, double-blind, placebo-controlled trial of low dose endotoxin. The low dose endotoxin challenge induces a transient systemic inflammatory response with normalization of cytokine levels within hours. This "phasic" inflammation is distinct from chronic ("tonic") levels of inflammation that may be present with AUD. A total of 38 non-treatment seeking heavy drinking men and women and 38 light drinking healthy controls will participate in the study. Recruitment will be monitored to ensure the two groups are matched by gender. Eligible participants will be randomly assigned, stratified by gender and BDI-II severity, to receive a single I.V. infusion of either low dose endotoxin (0.8 ng/kg of body weight) or placebo (same volume of 0.9% saline solution) at the UCLA Outpatient Clinical and Translational Research Center (CTRC). All participants will complete an alcohol cue-exposure paradigm and reward responsiveness assessment 2 hours post infusion, which is the time of expected peak cytokine response. All participants will also complete an fMRI alcohol cue-reactivity paradigm at 3 hours post infusion. Plasma levels of proinflammatory 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 four hours post infusion.
Eligibility Criteria
Inclusion Criteria
- Be between the ages of 21 and 45
- Be non-treatment seeking for AUD
- Have had at least one alcoholic beverage in the last 30 days
- FOR HEAVY DRINKERS: Alcohol Use Disorder Identification Test (AUDIT) score between 8 - 15; FOR LIGHT DRINKERS: AUDIT score 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
- Have non-removable ferromagnetic objects in body
- Have claustrophobia
- Have serious head injury or prolonged period of unconsciousness (>30 minutes)
Exclusionary Criteria for Inflammatory Challenge Visits:
- BrAC > 0.000 g/dl
- clinical withdrawal (CIWA-R) score ≥ 8
- blood pressure ≤ 90/60 or ≥ 160/120
- resting pulse ≤ 50 beats/minute or > 100 beats/minute
- temperature ≥ 99.5°F
- recent (past 2 weeks) acute illness or vaccination
- score of 10+ on Physical Sickness Symptoms Assessment
Data sourced from ClinicalTrials.gov (NCT04310423). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.