Intermittent Explosive DisorderPhase 2NCT06118567
Effect of Nitrous Oxide on Aggression.
A Phase 2 study testing Nitrous oxide and Room Air in people with Intermittent Explosive Disorder, run by Ohio State University at 1 site in United States.
Trial summary
The goal of this experimental medicine clinical trial is to test the hypothesis that nitrous oxide inhalation will result in a change in neurocircuit function in healthy controls and in individuals with impulsive aggressive tendencies. Read more about this study
- Who is it for?
- Ages 21 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Intermittent Explosive Disorder
- What is being tested?
- Nitrous oxide and Room Air
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- 6 Sep 2022to 31 Aug 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- All participants:
- Between 21 and 55 years of age.
- Physically healthy (no clinically significant medical condition as confirmed by medical history/physical exam).
- Able to give informed consent.
- Aggressive (IED) Study Participants (n = 25 Completed; 75 Enrolled).
- Current DSM-5 Criteria for IED
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- LHA Aggression scores > 12
- Negative for a history of psychosis, bipolar disorder, developmental disorder, intellectual disability or a current substance use disorder.
- Healthy, Non-Aggressive, Controls (n = 25 Completed, 75 Enrolled).
- Do not meet current/lifetime DSM-5 Criteria for any psychiatric disorder
- LHA aggression scores < 12
Who cannot join
- PCL Screening Version Score > 13; i.e., subject is likely to be psychopathic.32
- Current DSM-5 Major Depressive Episode.
- Life history of bipolar disorder/schizophrenia/organic mental syndrome.
- Intellectual disability [i.e., IQ < 70].
- History of N2O abuse/dependence.
- Clinically significant medical condition.
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- Current alcohol/drug use disorder of moderate or severe severity (i.e., subject is not in full remission from moderate to severe alcohol/drug use).
- Two weeks free of antipsychotic medication. (Note: Because a large number of individuals with aggressive tendencies in the community are already taking SSRIs, SNRIs, or mood stabilizers, these individuals will not be excluded if they continue to report impulsive aggressive behaviors at time of study.)
- Unwilling/unable to sign informed consent document.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Julian Roberts, R.N. contact
United States1 site, 1 recruiting
- Recruiting
Ohio State University Wexner Medical Center
Columbus, Ohio, 43210
About this study
Official title: Nitrous Oxide and Cortico-Limbic Function in Aggression
The goal of this experimental medicine clinical trial is to test the hypothesis that nitrous oxide inhalation will result in a change in neurocircuit function in healthy controls and in individuals with impulsive aggressive tendencies. The main question aims to answer are: Does Nitrous Oxide normalize brain circuit function in impulsively aggressive individuals 24 hours after inhalation. Participants will undergo a 60 minute inhalation session with 50% Nitrous Oxide (or room air at another session) and then undergo an fMRI scan 24 hours later. Researchers will compare healthy controls and impulsively aggressive individuals to see if Nitrous Oxide can normalize the function of cortico-limbic circuits in the latter group.
Read the detailed description
This study is designed to see if inhalation of 50% nitrous oxide (N2O) also known as laughing gas, can normalize cortico-limbic circuit functioning in impulsively aggressive human subjects. If the study results are positive, it would allow further studies of this potential treatment modality for those with recurrent, problematic, impulsive aggressive behavior (Intermittent Explosive Disorder: IED). IED is a disorder in which there are frequent and sudden outbursts of anger (yelling, throwing and breaking things, hitting people) that lead to problems with other people socially or at work. It affects about 4% of the US population lifetime, and does not have any approved treatments. The study will test if N2O can normalize brain activity 24 hours after infusion, in participants with a diagnosis of IED compared with healthy, non-aggressive, controls. This is a double-blinded-randomized study with comparison between groups (controls and IED patients) and comparison for each participant between N2O and placebo (air) inhalation. Participants will receive one type of inhalation 24 hours before undergoing an fMRI. Participants will be randomized to the order in which they receive N2O or air. Participants and study personnel involved in collection of outcome measures will be blinded to the type of inhalation. The study includes up to 7 visits. Visits 1/2 include interviews and questionnaires. At visits 3 and 5, participants receive the N2O or air inhalation. At visits 4 and 6, participants undergo fMRI while completing computer tasks. Visit 7 is to assure data collection is complete.
- Conditions
- Intermittent Explosive Disorder
- Being tested
- Nitrous oxide, Room Air
- Keywords
- IED
- Medical subject headings
- Disruptive, Impulse Control, and Conduct Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nitrous oxideDrug
Nitrous oxide gas.
Room AirDrug
Room Air
| Study group | Role | What they receive |
|---|---|---|
| Nitrous Oxide Inhalation | Active comparator | 60 minute session inhaling Nitrous Oxide gas. Receives: Drug: Nitrous oxide |
| Room Air | Sham comparator | 60 minute session inhaling Room Air. Receives: Drug: Room Air |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cortico-Limbic Response to Anger Faces
Orbito-Frontal and Amygdala responses to Anger Faces in fMRI
Measured: 24 hours after Nitrous Oxide and Room Air
Brain Connectivity
Resting State
Measured: 24 hours after Nitrous Oxide and Room Air
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Nov 2023
- Study start6 Sep 2022
- Primary completion31 Aug 2027 (estimated)
- Study completion31 Aug 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Intermittent Explosive DisorderStudies of the same condition, open and under way.
- More trials run by Ohio State UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ohio State University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Principal investigator, Emil Coccaro, Ohio State University
- Investigators
- Emil Coccaro, M.D., Principal investigator, Ohio State University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06118567
- Sponsor's protocol ID
- 2020H0368
- Status last verified
- Mar 2025
- First submitted
- 1 Nov 2023
- Last updated
- 27 Mar 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Nitrous Oxide and Cortico-Limbic Function in Aggression
- ClinicalTrials.gov ID
- NCT06118567
- Acronym / sponsor ID
- 2020H0368
- Conditions
- Intermittent Explosive Disorder
- Keywords
- IED
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Ohio State UniversityUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- 6 Sep 2022 (actual)
- Primary completion
- 31 Aug 2027 (estimated)
- Study completion
- 31 Aug 2027 (estimated)
- First posted
- 7 Nov 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this experimental medicine clinical trial is to test the hypothesis that nitrous oxide inhalation will result in a change in neurocircuit function in healthy controls and in individuals with impulsive aggressive tendencies. The main question aims to answer are: Does Nitrous Oxide normalize brain circuit function in impulsively aggressive individuals 24 hours after inhalation. Participants will undergo a 60 minute inhalation session with 50% Nitrous Oxide (or room air at another session) and then undergo an fMRI scan 24 hours later. Researchers will compare healthy controls and impulsively aggressive individuals to see if Nitrous Oxide can normalize the function of cortico-limbic circuits in the latter group.
Detailed description
This study is designed to see if inhalation of 50% nitrous oxide (N2O) also known as laughing gas, can normalize cortico-limbic circuit functioning in impulsively aggressive human subjects. If the study results are positive, it would allow further studies of this potential treatment modality for those with recurrent, problematic, impulsive aggressive behavior (Intermittent Explosive Disorder: IED). IED is a disorder in which there are frequent and sudden outbursts of anger (yelling, throwing and breaking things, hitting people) that lead to problems with other people socially or at work. It affects about 4% of the US population lifetime, and does not have any approved treatments. The study will test if N2O can normalize brain activity 24 hours after infusion, in participants with a diagnosis of IED compared with healthy, non-aggressive, controls. This is a double-blinded-randomized study with comparison between groups (controls and IED patients) and comparison for each participant between N2O and placebo (air) inhalation. Participants will receive one type of inhalation 24 hours before undergoing an fMRI. Participants will be randomized to the order in which they receive N2O or air. Participants and study personnel involved in collection of outcome measures will be blinded to the type of inhalation. The study includes up to 7 visits. Visits 1/2 include interviews and questionnaires. At visits 3 and 5, participants receive the N2O or air inhalation. At visits 4 and 6, participants undergo fMRI while completing computer tasks. Visit 7 is to assure data collection is complete.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Nitrous Oxide Inhalation | Active comparator | Drug: Nitrous oxide60 minute session inhaling Nitrous Oxide gas. |
| Room Air | Sham comparator | Drug: Room Air60 minute session inhaling Room Air. |
Who may qualify
- Ages
- 21 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (11 listed)
- Between 21 and 55 years of age.
- Physically healthy (no clinically significant medical condition as confirmed by medical history/physical exam).
- Able to give informed consent.
- Aggressive (IED) Study Participants (n = 25 Completed; 75 Enrolled).
- Current DSM-5 Criteria for IED
Key exclusion criteria (9 listed)
- PCL Screening Version Score > 13; i.e., subject is likely to be psychopathic.32
- Current DSM-5 Major Depressive Episode.
- Life history of bipolar disorder/schizophrenia/organic mental syndrome.
- Intellectual disability [i.e., IQ < 70].
- History of N2O abuse/dependence.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Nitrous oxideNitrous oxide gas. | Drug | Nitrous Oxide Inhalation |
| Room AirRoom Air | Drug | Room Air |
Primary outcome
Cortico-Limbic Response to Anger Faces
Time frame: 24 hours after Nitrous Oxide and Room Air
Orbito-Frontal and Amygdala responses to Anger Faces in fMRI
Brain Connectivity
Time frame: 24 hours after Nitrous Oxide and Room Air
Resting State
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Mar 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Julian Roberts, R.N. contact
Emil Coccaro, M.D. principal investigator
Ohio State University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nitrous oxide and Room Air in people with Intermittent Explosive Disorder, run by Ohio State University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 27 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jayla Copland, B.A. (614-327-1707, jayla.copland@osumc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cortico-Limbic Response to Anger Faces (time frame: 24 hours after Nitrous Oxide and Room Air). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Mar 2025.