SMILE Trial - Imaging Sub-Study

Completed

• Conditions: Major Depressive Disorder
• Interventions: Drug: Nitrous oxide gas for inhalation; Drug: Midazolam injection

• Registration Number: NCT05528718
• Lead Sponsor: Unity Health Toronto

Brief 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.

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 Timeline

• Study First Submitted: 2022-09-02
• Study First Submitted QC: 2022-09-02
• Study First Posted: 2022-09-06
• Study Start: 2023-03-07
• Primary Completion: 2024-03-30
• Status Verified: 2024-06
• Study Completion: 2024-06-14
• Last Update Submitted: 2024-06-17
• Last Update Posted: 2024-06-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 11

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)

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Experimental group	Nitrous oxide gas for inhalation	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.
Placebo group	Midazolam injection	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.

Primary Outcome Measures

Name	Time	Method
Brain functional activity and connectivity	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.

Trial Locations

Locations (1)

St. Michael's Hospital; 🇨🇦 Toronto, Ontario, Canada