Effect of Endotoxin on Alcohol Consumption

• ClinicalTrials.gov Identifier: NCT04527185
• Recruitment Status: Recruiting
• First Posted: August 26, 2020
• Last Update Posted: March 2, 2022
• Sponsor: Yale University
• Collaborator: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
• Information provided by (Responsible Party): Terril Verplaetse, Yale University

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Alcohol Use Disorder	Drug: Endotoxin	Phase 2

Detailed Description:

This pilot study is a double-blind, placebo-controlled design, which will compare endotoxin (0.4ng/kg i.v.) to placebo (0.0ng/kg) in non-treatment seeking adults meeting criteria for DSM-5 alcohol use disorders (n=32 total, n=16 per group).

Eligibility screening consists of an intake session and a physical exam. Participants meeting eligibility criteria will be randomized to receive a single dose of 0.4ng/kg i.v. endotoxin or placebo during a single laboratory session to evaluate ad-libitum alcohol consumption.

During the laboratory session, endotoxin (or placebo) administration will precede a 2-hour alcohol self-administration period.

Participants will be scheduled for a follow-up appointment to evaluate drinking behavior.

Adverse events are evaluated during the laboratory session and follow-up, and will be tabulated.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 32 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Other
• Official Title: Does Endotoxin Administration Increase Alcohol Consumption in Individuals With AUD?
• Actual Study Start Date: February 7, 2022
• Estimated Primary Completion Date: September 30, 2023
• Estimated Study Completion Date: September 30, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Endotoxin; Endotoxin (0.4ng/kg i.v.) will be administered one time during the laboratory session.	Drug: Endotoxin; Endotoxin 0.4ng/kg i.v.; Other Name: Lipopolysaccharide
Placebo Comparator: Placebo; Administered one time during the laboratory session.	Drug: Endotoxin; Endotoxin 0.4ng/kg i.v.; Other Name: Lipopolysaccharide

Outcome Measures

Primary Outcome Measures :

1. Alcohol consumption [ Time Frame: 120 minutes ]
   Mean mls of alcohol consumed for endotoxin and placebo groups during 120 minute alcohol self-administration session.

Eligibility Criteria

• Ages Eligible for Study: 21 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

1. Age 21-65;
2. Able to read and write English;
3. Meets DSM-5 criteria for current (past 6 months) alcohol use disorder;
4. 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.
5. Must meet drinking criteria during a consecutive 30-day period within the 90 days prior to baseline;
6. 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).

Exclusion Criteria:

1. 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;
2. Current DSM-5 substance use disorders, other than alcohol or nicotine;
3. A positive test result at intake appointment on urine drug screens conducted for illicit drugs, excluding cannabis;
4. Past 30 day use of psychoactive drugs including anxiolytics and antidepressants;
5. 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);
6. Suicidal, homicidal or evidence of current (past 6-month) severe mental illness such as schizophrenia, bipolar disorder or major depression, or anxiety disorders;
7. Subjects treatment-seeking or who are currently in treatment for alcohol use;
8. Subjects with medical conditions contraindicating alcohol use (e.g., liver enzymes ≥3× normal);
9. 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;
10. 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.

Contacts and Locations

Contacts

Contact: Terril Verplaetse, PhD; 203-737-6496; terril.verplaetse@yale.edu

Contact: Meaghan Lavery; 203-737-2783; meaghan.lavery@yale.edu

Locations

United States, Connecticut

Yale School of Medicine; Recruiting

New Haven, Connecticut, United States, 06519

Contact: Terril L Verplaetse, PhD

Sponsors and Collaborators

Yale University

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Investigators

• Principal Investigator: Terril Verplaetse, PhD; Yale University

More Information

• Responsible Party: Terril Verplaetse, Assistant Professor, Yale University
• ClinicalTrials.gov Identifier: NCT04527185
• Other Study ID Numbers: 2000028772; 1R03AA028361-01A1 ( U.S. NIH Grant/Contract )
• First Posted: August 26, 2020
• Last Update Posted: March 2, 2022
• Last Verified: February 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Alcoholism; Alcohol Drinking; Drinking Behavior; Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders