A Phase 2 interventional study of Endotoxin (E. coli O:113, Reference Endotoxin) and Saline (Placebo) in Intermittent Explosive Disorder, sponsored by Ohio State University. Recruiting at 1 site in United States. Open to participants aged 21 Years to 55 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-03-27.
Sponsored by Ohio State University · Phase 2, Interventional, and Basic science
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:
Participants will:
While elevations of circulating pro-inflammatory modulators correlate directly with variables of aggression, and direct application of cytokines to specific cortico- limbic regions in animals elicit aggressive responding, no studies have tested the hypothesis that acute increases in pro-inflammatory modulators can/will increase aggressive behavior in humans. The investigators aim to demonstrate a causal relationship between pro-inflammatory cytokines and aggression in human subjects by showing that an acute pro-inflammatory state, via endotoxin challenge, will increase aggressive responding, anger ratings, and hostile social cognition, to a greater degree in "aggressive" (n = 45), compared with "non-aggressive" (n = 45), individuals with mood/anxiety/ stress-related and/or personality disorders. The proposed study is a double-blind comparison of endotoxin/placebo challenge in the same individuals (within-subject) as a function of aggression status. Aggressive individuals will have high lifetime aggression (> 12 on Life History of Aggression: LHA) and be positive for an average of two anger attacks per week and/or three anger attacks per year that include physical assault of another person and/or or non-trivial destruction of property. "Non-Aggressive" individuals will be similar diagnostically but will have low lifetime aggression. "Aggressive responding" will be assessed using the Taylor Aggression Paradigm (TAP), "Anger" will be assessed by self-reported assessments (Profile of Mood States: POMS), and "Hostile Social Cognition" will be assessed by the Video-Social and Emotional Information Processing (V-SEIP) paradigm. The primary plasma pro-inflammatory outcome measures will be a composite of CRP, IL-6, IL-8, and TNF-α (as in the investigators' previous studies). MRI scans will including task-based scans involving "explicit" and "ambiguous" social threat. The investigators hypothesize that aggressive responding, anger ratings, and hostile social cognition (Primary Outcomes) and Composite Plasma Pro-Inflammatory Marker levels (Secondary Outcome), will be greater after endotoxin, compared with placebo, and will be greater in "aggressive" than "non- aggressive" study participants. The Investigators also hypothesize that these variables will correlate with dimensional measures of aggression. In addition, the investigators hypothesize that amygdala responses to explicit social threat (anger faces) will be enhanced (greater BOLD fMRI signal response) after Endotoxin, and that cortico-limbic responses to ambiguous social threat (V-SEIP) will be reduced (i.e., lesser BOLD fMRI signal response) in all study participants but reduced to a greater extent in "aggressive", compared with "non- aggressive", study participants. Finally, the investigators hypothesize that the pro-inflammatory effects of the endotoxin challenge will result in reduced connectivity between the functional edges supporting higher aggressive behavior and that endotoxin challenge will facilitate stronger connections among nodes associated with low aggressive behavior. If supported, this study will provide a strong rationale for clinical trials of anti-inflammatory agents in impulsive aggressive individuals.
56 studies on the registry are indexed under Disruptive, Impulse Control, and Conduct Disorders; 17 are open to participants now.
This study's planned enrollment of 112 is above the median of 48 across 46 interventional studies indexed under Disruptive, Impulse Control, and Conduct Disorders.
Browse Disruptive, Impulse Control, and Conduct Disorders studies →Ohio State University is the lead sponsor of 663 studies on the registry; 148 are open to participants now.
Of its 67 completed or terminated interventional studies of FDA-regulated products, 49 (73%) have results posted.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
"Aggressive Subjects" will have a current 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 .
Participant is physically healthy as confirmed by medical history, physical evaluation, and (in females) a negative pregnancy test.
Exclusion Criteria:
Participants with a current 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 /PTTa).
Participants with Bradycardia (i.e., heart rate \< 50 beats/minute) or other Grade 2 or higher abnormality.
Participants with conditions (e.g., asthma, psoriasis, etc.)
Participants who are .
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 must remain abstinent or agree to use a highly effective form of (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 , to receiving endotoxin.
Current treatment with opiates or any agents that affect pain threshold (exclusionary for the TAP).
Unwilling/unable to sign document.
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The American Psychiatric Association’s manual of mental health diagnoses. DSM-5 (2013, revised as DSM-5-TR in 2022) replaced DSM-IV, and some studies still name the older edition. “Meets DSM criteria for …” means diagnosed by that edition’s diagnostic criteria, usually by a clinician in an interview.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.
Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
DSM diagnostic criteria
The American Psychiatric Association’s manual of mental health diagnoses. DSM-5 (2013, revised as DSM-5-TR in 2022) replaced DSM-IV, and some studies still name the older edition. “Meets DSM criteria for …” means diagnosed by that edition’s diagnostic criteria, usually by a clinician in an interview.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
INR, PT and aPTT (clotting tests)
Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.
Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECG (electrocardiogram)
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Autoimmune disease
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Subjects with Intermittent Explosive Disorder (IED)
Biological: Endotoxin (E. coli O:113, Reference Endotoxin) · Other: Saline (Placebo)
Subjects without IED
Biological: Endotoxin (E. coli O:113, Reference Endotoxin) · Other: Saline (Placebo)
Dosage of endotoxin is 0.8 ng/Kg body Weight
Volume of saline to be the same as volume of endotoxin
Profile of Mood States (POMS) - Anger
Self-report questionnaire of "anger". Scale goes form 0-48 with higher scores meaning greater anger.
Time frame: Before and during the Endotoxin/Placebo Infusion for up to six hours only on ach of the two study days..
Taylor Aggression Paradigm (TAP)
An analog assessment of aggression widely used in human studies of aggression. This is the number of times that a selection of higher and very-high shock was set by the subject against the "confederate".
Time frame: Done once during the endotoxin (and placebo) infusion only. The TAP takes about 30 minutes.
Video-Social Emotional Information Processing (V-SEIP)
A computer-delivered task that assesses hostile attributional bias and negative emotional response to ambiguous social threat. The scores range from 0-3 with the higher numbers mean the more hostile attribution and negative emotional response.
Time frame: Done one during the endotoxin (and placebo) infusion only. The V-SEIP takes about 30 minutes on each of the two study days..
Pro-Inflammatory Cystokines (IL-6, THN-Alpha)
These are pro-inflammatory cytokines that are stimulated for release by endotoxin. These values range from 0 to \> 100 with the higher values representing greater inflammation.
Time frame: Prior to and after infusion of endotoxin and placebo for up to six hours only on each of the two study days.
Functional MRI
BOLD Signal Response to Explicit (Anger Faces), and to Ambiguous, Social Threat.
Time frame: Once during the Endotoxin Infusion and once during the Salin Infusion only. The MRI scan takes 90 minutes on each of the two study days.
Plan to share: Yes — Only de-identifed data will be shared.
Time frame: Start date: Only after the study is completed and data analysis has been completed.
Access criteria: University faculty at US and International Institutions. Only de-identified data will be released as data files.
No publications or documents are linked to this record.
Started Feb 2026 (actual). Primary completion is estimated for Jul 2029, 41 months after the start.
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