How mild inflammation affects impulsive aggression
Inflammatory Challenge in Human Aggression.
We will test whether a low-dose inflammatory infusion (endotoxin) increases anger, hostile thinking, and aggressive behavior in adults with intermittent explosive disorder compared with similar adults without that history.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 112 (estimated) |
| Ages | 21 Years to 55 Years |
| Sex | All |
| Sponsor | Ohio State University Academic / other |
| Locations | 1 site (Columbus, Ohio) |
| Trial ID | NCT06665074 on ClinicalTrials.gov |
What this trial studies
This double-blind, within-subject Phase 2 trial gives each participant a low-dose endotoxin infusion and a saline placebo on separate occasions and compares responses across sessions. The study enrolls two groups (about 45 people with high lifetime aggression and a current diagnosis of Intermittent Explosive Disorder, and about 45 matched non-aggressive controls) and measures self-reported anger, laboratory aggressive responding (Taylor Aggression Paradigm), hostile attribution (V-SEIP), and plasma pro-inflammatory cytokines. Participants are healthy adults aged 21–55, medically screened, and not taking excluded medications or having current major comorbid psychiatric disorders. The aim is to test whether acute inflammation causally increases anger and aggressive behavior more in the aggressive group than in controls.
Who should consider this trial
Good fit: Ideal candidates are physically healthy adults aged 21–55 who either have current Intermittent Explosive Disorder with high lifetime aggression (LHA > 12) for the aggressive arm, or similar-diagnosed adults without IED and low LHA scores (< 11) for the control arm.
Not a fit: People with current major depression, PTSD, panic disorder, generalized anxiety disorder, significant medical conditions, pregnancy, or those taking excluded prescription medications are not eligible and likely would not benefit from participating.
Why it matters
Potential benefit: If successful, the study could clarify a causal link between inflammation and impulsive aggression and point to new treatment targets or prevention approaches.
How similar studies have performed: Animal experiments and human correlational studies link cytokines to aggressive behavior, but no prior human endotoxin challenge has directly tested whether acute inflammation causes increased aggression, making this a novel causal test.
Eligibility criteria
Show full inclusion / exclusion criteria
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.
Where this trial is running
Columbus, Ohio
- The Ohio State University Medical Center — Columbus, Ohio, United States (Recruiting)
Study contacts
- Principal investigator: Emil F. Coccaro, MD — The Ohio State University College of Medicine
- Study coordinator: Emil F. Coccaro, MD
- Email: emil.coccaro@osumc.edu
- Phone: 7738521338
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.