SMILE Trial - Imaging Sub-Study

This is a pilot sub-study of an ongoing trial comparing N2O to midazolam in MDD and will examine neuroimaging correlates of treatment response.

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Key information

Conditions

Major Depressive Disorder Depressive Disorder Depressive Disorder, Major Mental Disorders Mood Disorders

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Observational

Primary location

St. Michael's Hospital

Toronto, Ontario, M5B 1M8, Canada

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

Eligible for main nitrous oxide (SMILE) study

Exclusion criteria

Contraindication for undergoing MRI scans (e.g., hip circumference < 180 cm or metal in the body)

Treatment and study plan

Nitrous oxide gas for inhalation

Drug

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.

Other names: Nitrous oxide at an inspiratory concentration of 50% with concurrent intravenous saline (100mL)

Midazolam injection

Drug

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.

Other names: 50% oxygen with intravenous midazolam (0.02mg/kg in 100mL)

Primary outcomes

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.

Sponsors and collaborators

Lead sponsor

Unity Health Toronto

Other

Registry information

Official study title

Sustained Mood Improvement With Laughing Gas Exposure: A Randomized Controlled Pilot Trial - Sub-Study Protocol to Include Neuroimaging

Important dates

Study start: 2023
Primary completion: 2024
Study completion: 2024
First posted: Sep 6, 2022
Registry last updated: Mar 27, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.

Completed