Endotoxin for Alcohol Consumption Behavior

Overseen By Terril L Verplaetse, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Yale University

Must not be taking: Anxiolytics, Antidepressants

Disqualifiers: Hypertension, Seizures, Schizophrenia, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how endotoxin, a substance that can trigger immune responses, affects drinking behavior in people with alcohol use disorder. Participants will receive either endotoxin or a placebo (a harmless substance) during a lab session to observe any changes in their drinking habits. The study seeks adults who have been drinking heavily for the past few months, specifically those exceeding 14 drinks a week for men or 7 drinks for women and often consuming more in one sitting. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you've used psychoactive drugs like anxiolytics or antidepressants in the past 30 days.

Is there any evidence suggesting that this protocol is likely to be safe for humans?

Research has shown that people with alcohol use disorder (AUD) may have a weaker immune response to endotoxins. This results in a less pronounced increase in certain immune signals, such as TNF-α, IL-6, and IL-8. Although this might seem beneficial, endotoxins can still cause physical and mental discomfort. Thus, even with a milder immune response, other side effects may occur.

This trial is in Phase 2, indicating some evidence of the treatment's safety, with the main focus on its tolerability. Researchers are still assessing its safety for a broader population. Joining such a trial involves some risk but also offers an opportunity to contribute to scientific understanding. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Most treatments for alcohol consumption behavior focus on behavioral therapy or medications like naltrexone and acamprosate, which help reduce the urge to drink. But endotoxin is different because it introduces a novel approach by using a small dose of bacterial endotoxin to potentially influence alcohol consumption behavior. This treatment works by triggering the immune system, which might affect brain pathways related to alcohol cravings. Researchers are excited about endotoxin because it could offer a new way to address alcohol use disorders by targeting the immune system, an area not typically explored with current medications.

What evidence suggests that endotoxin is effective for reducing alcohol consumption?

Studies have shown that endotoxin might affect drinking habits by influencing the immune system. Research suggests that introducing endotoxin can reduce the usual inflammatory response in people with alcohol use disorder, weakening the body's typical reaction to inflammation. Additionally, evidence indicates that endotoxin might help decrease certain drinking-related behaviors. In this trial, participants will receive either endotoxin or a placebo to further investigate these effects. Although this research is ongoing, these findings suggest that endotoxin could alter how people with alcohol use disorder react to drinking. ^{1 3 6 7 8}

Who Is on the Research Team?

Terril Verplaetse, PhD

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

This trial is for adults aged 21-65 who can read and write English, meet the criteria for current alcohol use disorder, and have a specific pattern of drinking. Pregnant or nursing women, those on certain medications or with medical conditions that make alcohol dangerous are excluded.

Inclusion Criteria

I drink more than the specified weekly limit for my gender.

You have been diagnosed with a drinking problem in the past 6 months according to the DSM-5 guidelines.

I am between 21 and 65 years old.

Exclusion Criteria

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.

Current DSM-5 substance use disorders, other than alcohol or nicotine

I am not pregnant or nursing and use effective birth control or am surgically sterile/postmenopausal.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Treatment

Participants receive a single dose of endotoxin or placebo during a laboratory session

1 day

1 visit (in-person)

Follow-up

Participants are monitored for drinking behavior and adverse events after the laboratory session

1 week

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Endotoxin

Trial Overview

The study is investigating how endotoxin affects drinking behavior in people with alcohol use disorder. Participants will be observed in a controlled environment to see if endotoxin influences their alcohol consumption.

How Is the Trial Designed?

Group I: Endotoxin Experimental Treatment 1 Intervention

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

Group II: Placebo Placebo Group 1 Intervention

Administered one time during the laboratory session.

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Collaborator

Trials

865

Recruited

1,091,000+

Citations

1.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/40451996/

Inflammatory endotoxin challenge in individuals with alcohol ...

Results: Endotoxin led to an acute blunted pro-inflammatory (i.e., TNF-α, IL-6, and IL-8) response in individuals with AUD compared to controls ...

2.

clinicaltrials.gov

clinicaltrials.gov/ct2/show/NCT04527185

NCT04527185 | Effect of Endotoxin on Alcohol Consumption

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure.

3.

onlinelibrary.wiley.com

onlinelibrary.wiley.com/doi/10.1111/acer.70090?af=R

Inflammatory endotoxin challenge in individuals with ...

Endotoxin led to an acute blunted inflammatory response in individuals with AUD compared with controls. Endotoxin led to decreased behavioral ...

4.

nature.com

nature.com/articles/s41598-017-04669-7

Quantity of alcohol drinking positively correlates with serum ...

A recently published study showed that a single alcohol binge can increase serum endotoxin, disturb innate immune responses, and alter ...

5.

journals.plos.org

journals.plos.org/plosone/article?id=10.1371/journal.pone.0096864

Acute Binge Drinking Increases Serum Endotoxin and ...

Our novel data demonstrate that a single alcohol binge in normal subjects resulted in a rapid and transient increase in serum endotoxin levels and that even ...

6.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04527185

NCT04527185 | Effect of Endotoxin on Alcohol Consumption

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

7.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10623394/

Endotoxin-Induced Physiological and Psychological Sickness ...

The objective of this randomized, double-blind, placebo-controlled crossover study was to gain insight into potential post-acute physiological and psychological ...

8.

researchgate.net

researchgate.net/publication/392315566_Inflammatory_endotoxin_challenge_in_individuals_with_alcohol_use_disorder_and_controls

Inflammatory endotoxin challenge in individuals with ...

Results Endotoxin led to an acute blunted pro‐inflammatory (i.e., TNF‐α, IL‐6, and IL‐8) response in individuals with AUD compared to controls (all p's < 0.039) ...