Effect of Endotoxin on Alcohol Consumption

NCT04527185 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 20000287721R03AA028361-01A1
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Alcohol Use Disorder

Outcome Measures

Primary Outcomes (1)

• Alcohol Consumption

  Mean mls of alcohol consumed for endotoxin and placebo groups during 120 minute alcohol self-administration session.

  120 minutes

Study Arms (2)

Endotoxin

EXPERIMENTAL

Endotoxin (0.4ng/kg i.v.) will be administered one time during the laboratory session.

Drug: Endotoxin

Placebo

PLACEBO COMPARATOR

Administered one time during the laboratory session.

Drug: Endotoxin

Interventions

Endotoxin DRUG

Endotoxin 0.4ng/kg i.v.

Also known as: Lipopolysaccharide

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:

• Age 21-65;
• Able to read and write English;
• Meets DSM-5 criteria for current (past 6 months) alcohol use disorder;
• 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.
• Must meet drinking criteria during a consecutive 30-day period within the 90 days prior to baseline;
• 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).
• Negative urine pregnancy test for women.

You may not qualify if:

• 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;
• Current DSM-5 substance use disorders, other than alcohol or nicotine;
• A positive test result at intake appointment on urine drug screens conducted for illicit drugs, excluding cannabis;
• Past 30 day use of psychoactive drugs including anxiolytics and antidepressants;
• 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);
• Suicidal, homicidal or evidence of current (past 6-month) severe mental illness such as schizophrenia, bipolar disorder or major depression, or anxiety disorders;
• Subjects treatment-seeking or who are currently in treatment for alcohol use;
• Subjects with medical conditions contraindicating alcohol use (e.g., liver enzymes ≥3× normal);
• 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;
• 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.
• Subjects \>38 on the Alcohol Use Disorders Identification Test (AUDIT)
• Subjects with resting pulse \>100 at challenge
• Subjects with recent (past 2 weeks) acute illness or vaccination
• Subjects with \>Grade 2 laboratory abnormalities on screening

Sponsors & Collaborators

• Yale University: lead
• National Institute on Alcohol Abuse and Alcoholism (NIAAA): collaborator

Study Sites (1)

Yale School of Medicine

New Haven, Connecticut, 06519, United States

Location

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

Limitations and Caveats

Aims on this project were disrupted due to COVID-19 and supplier issues with endotoxin: Clinical research at Yale resumed as of August 1, 2021. Further, there was a significant delay in obtaining endotoxin for use in human subjects. The investigators supply from NIH was depleted and organizing and ordering additional endotoxin from List Laboratories (along with all the regulatory paperwork) took longer than expected. Investigators were without endotoxin from 5/2021 to 1/2023.

Results Point of Contact

• Title: Terril Verplaetse
• Organization: Yale School of Medicine

terril.verplaetse@yale.edu

203-737-6496

Study Officials

• Terril Verplaetse, PhD

  Yale University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: August 21, 2020
• First Posted: August 26, 2020
• Study Start: February 27, 2022
• Primary Completion: October 31, 2024
• Study Completion: October 31, 2024
• Last Updated: November 3, 2025
• Results First Posted: November 3, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)