Inflammatory Challenge in Human Aggression.

NCT06665074 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 2023H0217R01MH133925-01A1
• Study Type: interventional
• Target: 112
• Locations: 1 country
• Sites: 1

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

Keywords

IED; Inflammation; Cytokines; Aggression

Outcome Measures

Primary Outcomes (1)

• Profile of Mood States (POMS) - Anger

  Self-report questionnaire of "anger". Scale goes form 0-48 with higher scores meaning greater anger.

  Before and during the Endotoxin/Placebo Infusion for up to six hours only on ach of the two study days..

Secondary Outcomes (4)

• Taylor Aggression Paradigm (TAP)

  Done once during the endotoxin (and placebo) infusion only. The TAP takes about 30 minutes.

• Video-Social Emotional Information Processing (V-SEIP)

  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)

  Prior to and after infusion of endotoxin and placebo for up to six hours only on each of the two study days.

• Functional MRI

  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.

Study Arms (2)

Aggressive Subjects

EXPERIMENTAL

Subjects with Intermittent Explosive Disorder (IED)

Biological: Endotoxin (E. coli O:113, Reference Endotoxin); Other: Saline (Placebo)

Non-Aggressive Subjects

OTHER

Subjects without IED

Biological: Endotoxin (E. coli O:113, Reference Endotoxin); Other: Saline (Placebo)

Interventions

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

Dosage of endotoxin is 0.8 ng/Kg body Weight

Aggressive Subjects; Non-Aggressive Subjects

Saline (Placebo) OTHER

Volume of saline to be the same as volume of endotoxin

Aggressive Subjects; Non-Aggressive Subjects

Eligibility Criteria

• Age: 21 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• "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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ohio State University: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

The Ohio State University Medical Center

Columbus, Ohio, 43210, United States

RECRUITING

MeSH Terms

Conditions

Disruptive, Impulse Control, and Conduct Disorders; Inflammation; Aggression

Interventions

Endotoxins; Sodium Chloride

Condition Hierarchy (Ancestors)

Mental Disorders; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Aberrant Motor Behavior in Dementia; Behavioral Symptoms; Behavior; Social Behavior

Intervention Hierarchy (Ancestors)

Bacterial Toxins; Toxins, Biological; Biological Factors; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Emil F. Coccaro, MD

  The Ohio State University College of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Emil F. Coccaro, MD

CONTACT

7738521338; emil.coccaro@osumc.edu

Julian Roberts, RN

CONTACT

julian.roberts@osumc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Placebo (saline infusion)
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Psychiatry

Study Record Dates

• First Submitted: October 21, 2024
• First Posted: October 30, 2024
• Study Start: February 16, 2026
• Primary Completion (Estimated): July 1, 2029
• Study Completion (Estimated): January 1, 2030
• Last Updated: March 27, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• 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.

Locations

US (1)