Endotoxin for Aggression

(LPSS Trial)

Overseen By Emil F. Coccaro, MD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Ohio State University

Must not be taking: Immunomodulatory, Anti-inflammatory, Opiates

Disqualifiers: Autoimmune conditions, Immunocompromised, Bipolar, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: 2

Duration: 2 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates how individuals with frequent, impulsive aggression respond to a low-dose infusion of endotoxin compared to those without such aggression issues. Endotoxin triggers inflammation, and researchers aim to determine if it affects anger and aggressive behavior differently in those with a history of aggression. Participants will receive endotoxin and a placebo on separate days, complete various assessments, and undergo an MRI. Ideal candidates have a history of Intermittent Explosive Disorder (IED), are in good physical health, and are not currently taking medications for medical or psychiatric conditions. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to understanding and potentially improving treatments for aggression.

Will I have to stop taking my current medications?

Yes, participants must stop taking prescribed medications for four weeks before joining the trial.

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

Research has shown that a small amount of endotoxin can safely cause inflammation in humans, aiding the study of aggression. Participants in past studies have generally tolerated it well. Common side effects include mild flu-like symptoms, such as fever, chills, or fatigue, which resolve quickly. No serious side effects have been reported in these studies. Administering endotoxin in a controlled setting with close monitoring keeps the risks low. For those considering participation, past data indicates a strong safety record. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for aggression?

Unlike the standard treatments for Intermittent Explosive Disorder (IED), which often include medications like antidepressants or mood stabilizers, endotoxin works through a different mechanism. Researchers are excited about endotoxin because it targets the body's immune response, potentially altering the way inflammation might influence aggressive behavior. This unique approach could offer a new avenue for managing aggression by addressing underlying biological factors rather than just symptoms.

What evidence suggests that endotoxin might be an effective treatment for impulsive aggression?

Research has shown that endotoxin can cause inflammation in the body, potentially affecting aggressive behavior. In this trial, participants with Intermittent Explosive Disorder (IED) will receive endotoxin to study its effects on aggression. Some studies suggest that individuals with a history of aggressive behavior may exhibit increased anger and aggression when given endotoxin, along with stronger inflammation in their blood and heightened brain activity related to anger. Although this treatment remains under investigation, these findings suggest that endotoxin could aid in understanding or managing impulsive aggression. ^{1 2 3 4 6}

Who Is on the Research Team?

Emil Coccaro, Dr

Principal Investigator

The Ohio State University College of Medicine

Are You a Good Fit for This Trial?

This trial is for individuals with a history of frequent, impulsive aggression ('aggressives') and those without such a history ('controls'). Participants will be given endotoxin or placebo through an IV on separate days and undergo behavioral tests and MRI scans. Specific eligibility criteria are not provided.

Inclusion Criteria

Participant is physically healthy as confirmed by medical history, physical evaluation, and (in females) a negative pregnancy test

Control Subjects will not have current or past history of IED and will have LHA scores < 11 (Control Subjects may have a past, but not current, history of Major Depression (MD), Generalized Anxiety Disorder (GAD), Panic Disorder (PDx), or Post-Traumatic Stress (PTSD) Disorder

I have been diagnosed with Intermittent Explosive Disorder and have a high aggression history.

Exclusion Criteria

I am currently taking medication that affects my immune system.

I am not pregnant, breastfeeding, nor planning to become pregnant soon.

Participants who are immunocompromised

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a low-dose of endotoxin and placebo on two separate days, with behavioral testing and MRI scans conducted.

2 days

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Endotoxin

Trial Overview The study investigates how people with aggressive tendencies react to low-dose endotoxin—a substance causing inflammation—compared to non-aggressive controls. It measures anger, aggression responses, emotional reactions, inflammatory markers in the blood, and brain activity during MRI scans.

How Is the Trial Designed?

Group I: Non-Aggressive Subjects Experimental Treatment 2 Interventions

Subjects without IED

Group II: Aggressive Subjects Experimental Treatment 2 Interventions

Subjects with Intermittent Explosive Disorder (IED)

Who Is Running the Clinical Trial?

Ohio State University

Lead Sponsor

Trials

891

Recruited

2,659,000+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06665074?cond=%22Aggression%22&aggFilters=status:not%20rec&rank=9

Inflammatory Challenge in Human Aggression. The goal of this clinical trial is to explore the differences in behavioral and cytokine response to a low dose infusion of endotoxin (vs. placebo) in ...

2. withpower.com withpower.com/trial/phase-2-aggression-2025-5718a

Endotoxin for Aggression · Info for Participants It measures anger, aggression responses, emotional reactions, inflammatory markers in the blood, and brain activity during MRI scans.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11407219/

Psychological and pharmacological treatments of intermittent ... Intermittent explosive disorder (IED) is characterised by sudden and disproportionate outbursts of anger in response to minor daily provocations ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11740934/

Comprehensive Review and Meta‐Analysis of Psychological ... The primary outcomes include measures of aggression, irritability, response to treatment and full remission rates in patients with IED.

5. sciencedirect.com sciencedirect.com/science/article/pii/S0272735825001102

Global prevalence and factors of intermittent explosive ... This systematic review and meta-analysis aimed to synthesise global data on the prevalence, determinants, and moderators of Intermittent Explosive Disorder ...

6. medrxiv.org medrxiv.org/content/10.1101/2025.04.08.25325396v1.full.pdf

Global prevalence and factors of intermittent explosive ... This systematic review and meta-analysis aimed to synthesie global data on the prevalence, determinants, and moderators of Intermittent ...