Major Depressive DisorderNCT05528718
SMILE Trial - Imaging Sub-Study
An observational study of Major Depressive Disorder, run by Unity Health Toronto at 1 site in Canada.
Trial summary
This is a pilot sub-study of an ongoing trial comparing N2O to midazolam in MDD and will examine neuroimaging correlates of treatment response. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Major Depressive Disorder
- What is being tested?
- Nitrous oxide gas for inhalation and Midazolam injection
- Type of treatment
- Injection or infusion
- How many people
- 11 participants
- Where
- 1 siteCanada
- Study dates
- 7 Mar 2023to 14 Jun 2024
- Phase
- Observational
- Are there results?
- None posted in the registry
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 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patient participants were diagnosed as suffering from major depressive disorder (MDD) that meets the criteria of the Diagnosis and Statistical Manual for Mental Disorders (DSM-5), will be eligible to participate in this data collection study. Participants who have agreed to receive N2O treatments as part of the Interventional Psychiatry Clinical Program at St. Michael's Hospital will be approached and recruited.
Who may be able to join
- Eligible for main nitrous oxide (SMILE) study
Who cannot join
- Contraindication for undergoing MRI scans (e.g., hip circumference < 180 cm or metal in the body)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Sustained Mood Improvement With Laughing Gas Exposure: A Randomized Controlled Pilot Trial - Sub-Study Protocol to Include Neuroimaging
This is a pilot sub-study of an ongoing trial comparing N2O to midazolam in MDD and will examine neuroimaging correlates of treatment response.
Read the detailed description
Magnetic resonance imaging (MRI) scans of MDD-affected brains have revealed changes in structural and functional connectivity compared to healthy subjects. This pilot sub-study examines structural and functional connectivity associated with MDD-affected patient participants' responsiveness to N2O compared to the midazolam placebo, which induces similar sedative effects. The investigators intend to address the changes in brain functional activity and connectivity between baseline and after a four-week intervention course involving weekly nitrous oxide inhalations measured by MRI.
- Conditions
- Major Depressive Disorder
- Being tested
- Nitrous oxide gas for inhalation, Midazolam injection
- Medical subject headings
- Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nitrous oxide gas for inhalationDrug
Also called Nitrous oxide at an inspiratory concentration of 50% with concurrent intravenous saline (100mL)
This sub-study does not have an intervention and based on the main study the participants who have received N2O will be compared with the midazolam placebo group.
Midazolam injectionDrug
Also called 50% oxygen with intravenous midazolam (0.02mg/kg in 100mL)
This sub-study does not have an intervention and based on the main study the participants who have received N2O will be compared with the midazolam placebo group.
| Study group | Role | What they receive |
|---|---|---|
| Experimental group | Participants assigned to this intervention arm in the main study will have been administered nitrous oxide at an inspiratory concentration of 50% with concurrent intravenous saline (100mL) for one hour. Receives: Drug: Nitrous oxide gas for inhalation | |
| Placebo group | Participants assigned to this intervention arm in the main study will have been administered 50% oxygen with intravenous midazolam (0.02mg/kg in 100mL) for one hour. Receives: Drug: Midazolam injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Brain functional activity and connectivity
Changes in brain functional activity and connectivity between baseline and after 4 weeks of receiving the intervention, measured by MR imaging.
Measured: 4 weeks from the baseline visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Sep 2022
- Study start7 Mar 2023
- Primary completion30 Mar 2024
- Study completion14 Jun 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Unity Health Toronto
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Venkat Bhat, MD MSc, Principal investigator, Unity Health Toronto
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05528718
- Sponsor's protocol ID
- 22-139
- Status last verified
- Jun 2024
- First submitted
- 2 Sep 2022
- Last updated
- 27 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sustained Mood Improvement With Laughing Gas Exposure: A Randomized Controlled Pilot Trial - Sub-Study Protocol to Include Neuroimaging
- ClinicalTrials.gov ID
- NCT05528718
- Acronym / sponsor ID
- 22-139
- Conditions
- Major Depressive Disorder
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Unity Health TorontoUniversity, hospital or other
- Study start
- 7 Mar 2023 (actual)
- Primary completion
- 30 Mar 2024 (actual)
- Study completion
- 14 Jun 2024 (actual)
- First posted
- 6 Sep 2022 (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.
This is a pilot sub-study of an ongoing trial comparing N2O to midazolam in MDD and will examine neuroimaging correlates of treatment response.
Detailed description
Magnetic resonance imaging (MRI) scans of MDD-affected brains have revealed changes in structural and functional connectivity compared to healthy subjects. This pilot sub-study examines structural and functional connectivity associated with MDD-affected patient participants' responsiveness to N2O compared to the midazolam placebo, which induces similar sedative effects. The investigators intend to address the changes in brain functional activity and connectivity between baseline and after a four-week intervention course involving weekly nitrous oxide inhalations measured by MRI.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Experimental group | – | Drug: Nitrous oxide gas for inhalationParticipants assigned to this intervention arm in the main study will have been administered nitrous oxide at an inspiratory concentration of 50% with concurrent intravenous saline (100mL) for one hour. |
| Placebo group | – | Drug: Midazolam injectionParticipants assigned to this intervention arm in the main study will have been administered 50% oxygen with intravenous midazolam (0.02mg/kg in 100mL) for one hour. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patient participants were diagnosed as suffering from major depressive disorder (MDD) that meets the criteria of the Diagnosis and Statistical Manual for Mental Disorders (DSM-5), will be eligible to participate in this data collection study. Participants who have agreed to receive N2O treatments as part of the Interventional Psychiatry Clinical Program at St. Michael's Hospital will be approached and recruited.
Key inclusion criteria (1 listed)
- Eligible for main nitrous oxide (SMILE) study
Key exclusion criteria (1 listed)
- Contraindication for undergoing MRI scans (e.g., hip circumference < 180 cm or metal in the body)
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 oxide gas for inhalationAlso: Nitrous oxide at an inspiratory concentration of 50% with concurrent intravenous saline (100mL)This sub-study does not have an intervention and based on the main study the participants who have received N2O will be compared with the midazolam placebo group. | Drug | Experimental group |
| Midazolam injectionAlso: 50% oxygen with intravenous midazolam (0.02mg/kg in 100mL)This sub-study does not have an intervention and based on the main study the participants who have received N2O will be compared with the midazolam placebo group. | Drug | Placebo group |
Primary outcome
Brain functional activity and connectivity
Time frame: 4 weeks from the baseline visit
Changes in brain functional activity and connectivity between baseline and after 4 weeks of receiving the intervention, measured by MR imaging.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Mar 2026.
- 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. This study is not recruiting at the moment.
Venkat Bhat, MD MSc principal investigator
Unity Health Toronto
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Major Depressive Disorder, run by Unity Health Toronto at 1 site in Canada.
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 1 inclusion and 1 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: finished, as of the sponsor's last update on 27 Mar 2026. 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 Canada. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Brain functional activity and connectivity (time frame: 4 weeks from the baseline visit). 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 2026; AzTrials last refreshed its copy on 29 Oct 2026.