Adults 21 to 45, any sex, with Alcohol Use Disorder or Inflammatory Response. Patients with the condition only — healthy volunteers not accepted.
Results — posted to ClinicalTrials.gov
Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.
Cue-induced CravingPrimary· The cue-reactivity paradigm is conducted at baseline and at 2 hours post-infusion of placebo or low dose endotoxin 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 abou
Baseline
Group
Value
95% CI
Placebo
4.5004
± 0.9622
Endotoxin
7.9081
± 0.9604
Two Hours Post-Baseline
Group
Value
95% CI
Placebo
4.5004
± 0.9622
Endotoxin
5.6178
± 0.9858
Change in Negative MoodPrimary· The POMS will be completed at 5 timepoints during the experimental visit. Specifically, negative mood will be assessed at baseline (prior to infusion) and 1 hour, 2 hours, 3 hours, and 4 hours post-infusion of placebo or low dose endotoxin.
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 w
Baseline
Group
Value
95% CI
Placebo
0.60
± 0.27
Endotoxin
0.80
± 0.36
One Hour Post-Baseline
Group
Value
95% CI
Placebo
0.50
± 0.34
Endotoxin
0.90
± 0.43
Two Hours Post-Baseline
Group
Value
95% CI
Placebo
0.50
± 0.27
Endotoxin
0.90
± 0.31
Three Hours Post-Baseline
Group
Value
95% CI
Placebo
1.70
± 0.88
Endotoxin
1.70
± 0.72
Four Hours Post-Baseline
Group
Value
95% CI
Placebo
0.90
± 0.53
Endotoxin
1.70
± 0.79
Change in Reward ResponsivenessSecondary· The RRS will be completed at 2 timepoints during the experimental visit. Specifically, reward responsiveness will be assessed at baseline (prior to infusion) and 2 hours post-infusion of placebo or low dose endotoxin.
The Reward Responsiveness Scale (RRS) measures self-report reward responsiveness. The RRS scale consists of 8 items on a 4-point scale, with the sum total score of items ranging from 8-32, where higher scores indicate higher reward responsiveness. The measure was completed electronically. The investigators are interested in whether low dose endotoxin will decrease reward responsiveness as compared to placebo.
RRS Baseline
Group
Value
95% CI
Placebo
25.60
± 1.11
Endotoxin
26.20
± 0.98
RRS Two Hours Post-Baseline
Group
Value
95% CI
Placebo
25.50
± 1.27
Endotoxin
26.22
± 1.24
Change in Reward ResponsivenessSecondary· The PRT will be completed at 2 timepoints during the experimental visit. Specifically, reward responsiveness will be assessed at baseline (prior to infusion) and 2 hours post-infusion of placebo or low dose endotoxin.
The Probabilistic Reward Task (PRT) is a signal detection learning task that assesses reward learning from which two subscales were derived: logd is a measure of discriminability, or how difficult it is for the subjects to discriminate between the signals, while logb is a measure of response bias, or subjects' preference for the response paired with the more frequent reward. Higher logd values indicate a better ability to discriminate between reward signals (logd=1⁄2 log(Richcorrect\*Leancorrect)/(Richincorrect\*Leanincorrect)). Higher logb values indicate better reward sensitivity (logb=1⁄2 l
PRT logd Baseline
Group
Value
95% CI
Placebo
1.46
± 0.13
Endotoxin
1.29
± 0.16
PRT logd Two Hours Post-Basleine
Group
Value
95% CI
Placebo
1.98
± 0.33
Endotoxin
1.27
± 0.16
PRT logb Baseline
Group
Value
95% CI
Placebo
-0.07
± 0.03
Endotoxin
0.16
± 0.05
PRT logb Two Hours Post-Baseline
Group
Value
95% CI
Placebo
0.31
± 0.38
Endotoxin
0.20
± 0.04
Effect on Neural Alcohol Cue-reactivitySecondary· The fMRI scan will be completed during the experimental visit. Specifically, participants will undergo the neuroimaging scan at 3 hours post-infusion of placebo or low dose endotoxin.
The fMRI scan will include a cue-reactivity paradigm in which participants will view images of alcoholic beverages, non-alcoholic beverages, negative images, and fixation cross. Participants will be asked to rate their alcohol craving before the scan and after each cue block. The investigators are interested in determining the effects of endotoxin on neural alcohol cue-reactivity. An alcohol beverage \> non-alcohol beverage contrast was specified in the first-level model for each subject, and FSL's FLAME 1 was used to conduct group-level analyses (endotoxin vs. placebo) to identify significant
Left Postcentral Gyrus Significant Cluster
Group
Value
95% CI
Placebo > Endotoxin (Alcohol vs. Beverage Cues) at T3
3190
Right Thalamus Significant Cluster
Group
Value
95% CI
Placebo > Endotoxin (Alcohol vs. Beverage Cues) at T3
1942
Left Inferior Temporal Gyrus Cluster
Group
Value
95% CI
Placebo > Endotoxin (Alcohol vs. Beverage Cues) at T3
931
Left/Right Precuneus Cluster
Group
Value
95% CI
Placebo > Endotoxin (Alcohol vs. Beverage Cues) at T3
920
Right Precentral Gyrus
Group
Value
95% CI
Placebo > Endotoxin (Alcohol vs. Beverage Cues) at T3
518
Adverse events — posted to ClinicalTrials.gov
Time frame: Adverse event data were collected throughout the study duration from 2021-2023..
Reporting threshold: 0%.
Adverse-event reports describe events observed during the trial — not all are caused by the drug.
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.
Publications & conference data
1 peer-reviewed publication reference this trial (live from Europe PMC):
Publications: Europe PMC API search by NCT ID, retrieved 10 June 2026
Drug + disease cross-links: matched in real time against Drug Landscape's normalised drug + company + condition tables
Sponsor: as reported to ClinicalTrials.gov by University of California, Los Angeles
Last refreshed: 1 May 2025
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