Recruiting
Phase 2

Endotoxin

Sponsor:

Ohio State University

Code:

NCT06665074

Conditions

Intermittent Explosive Disorder

Eligibility Criteria

Sex: All

Age: 21 - 55

Healthy Volunteers: Accepted

Interventions

Endotoxin (E. coli O:113, Reference Endotoxin)

Saline (Placebo)

Study Details

Brief summary:

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 individuals with histories of frequent, problematic, impulsive aggression ("aggressives") compared to similar individuals without this history ("controls"). Endotoxin is a substance that produces a reliable inflammation response in human subjects. The main questions it aims to answer are:

  • Do aggressive individuals have greater self-rated anger responses to low-dose endotoxin compared with controls?
  • Do aggressive individuals have greater analog aggressive responses (in the Taylor Aggression Paradigm) to low-dose endotoxin compared with controls?
  • Do aggressive individuals have greater hostile attributional and negative emotional responses (in the V-SEIP) to low-dose endotoxin compared with controls?
  • Do aggressive individuals have greater plasma pro-inflammatory responses to low-dose endotoxin compared with controls?
  • Do aggressive individuals display a greater activation of brain responses to anger-related picture during an MRI scan during low-dose endotoxin compared with controls? Researchers will compare endotoxin to a placebo (a look-alike substance that contains no drug) explore the differences in behavioral and cytokine response to a low dose infusion of endotoxin (vs. placebo) in individuals with histories of frequent, problematic, impulsive aggression ("aggressives") compared to similar individuals without this history ("controls").

Participants will:

  • Receive a low-dose of endotoxin and placebo on two (2) separate days. The study drugs will be given through a plastic tube inserted in a forearm vein.
  • Visit the laboratory on at least two (2) separate days to receive the endotoxin and placebo.
  • Complete rating forms, behavioral testing, and an MRI on each of the two (2) laboratory days.

Conditions

Intermittent Explosive Disorder

Study ID

NCT06665074

Start date

Feb 16, 2026

Status verified date

Mar, 2026

Completion date

Jan, 2030

Anticipated

Primary completion date

Jul, 2029

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 21 - 55

Healthy Volunteers: Accepted

Inclusion Criteria:

"Aggressive Subjects" will have a current DSM-5 diagnosis of Intermittent Explosive Disorder (IED) and have a Life History of Aggression (LHA) > 12.

"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.

Participant is between 21 and 55 years of age and is able to give informed consent.

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

Exclusion Criteria:

Participants with a current clinically significant medical condition.

Participants current co-morbid Major Depression (MD), Generalized Anxiety Disorder (GAD), Panic Disorder (PDx), or Post-Traumatic Stress (PTSD) Disorder.

Participants currently taking prescribed medications for an active medical or psychiatric condition.

Participants not free of prescribed medications for four weeks.

Participants with Grade 2 or higher abnormalities on clinical laboratory examination (e.g., CBC with Differential, Metabolic Panel, and PT/INR/PTTa).

Participants with Bradycardia (i.e., heart rate < 50 beats/minute) or other Grade 2 or higher ECG abnormality.

Participants with autoimmune conditions (e.g., asthma, psoriasis, etc.)

Participants who are immunocompromised.

Participants taking immunomodulatory, or anti-inflammatory, agents.

Participants that are pregnant, breastfeeding, or plan to become pregnant within nine months of enrollment in the study.

Female study participants of childbearing potential must remain abstinent or agree to use a highly effective form of contraception (e.g., an intrauterine device). Childbearing potential is defined as, study participants who have reached menarche and have not undergone a documented sterilization procedure (i.e., hysterectomy, bilateral oophorectomy, or salpingotomy), and have not reached menopause.

Life history of bipolar disorder / schizophrenia / organic mental syndrome, or intellectual disability.

Current alcohol / drug use disorder of greater than mild severity.

Current suicidal ideation.

History of a suicide attempt in the past year prior to study entry.

Life history of > 3 or more suicide attempts of any type.

Life history of any moderately severe suicide attempt.

Current or life history of homicidal ideation.

Current or life history of felony assault and/or battery.

Currently on parole for aggressive behavior.

Allergy, or contraindication, to receiving endotoxin.

Current treatment with opiates or any agents that affect pain threshold (exclusionary for the TAP).

Unwilling/unable to sign informed consent document.

Study Design

Enrollment

112 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Basic Science

Interventions and Outcome Measures

Arms

experimental: Aggressive Subjects

Subjects with Intermittent Explosive Disorder (IED)

other: Non-Aggressive Subjects

Subjects without IED

Interventions

Endotoxin (E. coli O:113, Reference Endotoxin)

Dosage of endotoxin is 0.8 ng/Kg body Weight

Saline (Placebo)

Volume of saline to be the same as volume of endotoxin

Primary outcome measure

  • Profile of Mood States (POMS) - Anger [ Time Frame: Before and during the Endotoxin/Placebo Infusion for up to six hours only on ach of the two study days.. ]

Central Contacts and Locations

Central contacts

Emil F. Coccaro, MD

7738521338emil.coccaro@osumc.edu

Julian Roberts, RN

julian.roberts@osumc.edu

Locations

The Ohio State University Medical Center

Recruiting

Columbus, Ohio, United States, 43210

Contacts

Emil Coccaro, MD

773-852-1338emil.coccaro@osumc.edu

Julian Roberts, RN

julian.roberts@osumc.edu

More Information

Sponsor

Ohio State University

Last update posted

Mar 27, 2026

Last verified

Mar, 2026

Keywords

  • IED
  • Inflammation
  • Cytokines
  • Aggression

Trial information was received from ClinicalTrials.gov and was last updated on 2026-10-23. This information was provided to ClinicalTrials.gov by Ohio State University on 2026-03-27. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.