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Nitrous Oxide 99 % for Depression (SMILE Trial)

Phase 4
Waitlist Available
Research Sponsored by Unity Health Toronto
Eligibility Criteria Checklist
Specific guidelines that determine who can or cannot participate in a clinical trial
Must have
Experiencing moderate to severe depressive episode (HAMD > 17)
Failure of two trials of antidepressant therapy of adequate dose and duration during the current depressive episode
Timeline
Screening 3 weeks
Treatment Varies
Follow Up 2 years
Awards & highlights

SMILE Trial Summary

This trial is testing a new, short-term treatment option for major depressive disorders using nitrous oxide gas. The study will compare nitrous oxide gas to an active placebo to see if it is an effective treatment option.

Who is the study for?
Adults aged 18-65 with major depressive disorder who haven't improved after two antidepressant treatments can join. They must not be pregnant, breastfeeding, or have a history of certain mental health conditions like schizophrenia. Participants should agree to use effective contraception and maintain their current antidepressant regimen.Check my eligibility
What is being tested?
The trial is testing if nitrous oxide gas can improve depression symptoms compared to an active placebo (oxygen + Midazolam). It's for those whose depression hasn't responded to standard treatments, with participants randomly assigned to either the study group or control group.See study design
What are the potential side effects?
Possible side effects include reactions related to inhaling nitrous oxide such as headaches, nausea, dizziness, and fatigue. Midazolam may cause drowsiness, reduced alertness, respiratory issues and in rare cases paradoxical reactions like anxiety.

SMILE Trial Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below
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I am experiencing a severe depressive episode.
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I have tried two different antidepressants without success during this depressive episode.
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I am between 18 and 65 years old.
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I have been diagnosed with a major depressive episode.
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I understand and can agree to the study's procedures and risks.
Select...
I have been diagnosed with Major Depressive Disorder.

SMILE Trial Timeline

Screening ~ 3 weeks
Treatment ~ Varies
Follow Up ~2 years
This trial's timeline: 3 weeks for screening, Varies for treatment, and 2 years for reporting.

Treatment Details

Study Objectives

Outcome measures can provide a clearer picture of what you can expect from a treatment.
Primary outcome measures
Adherence rate
Frequency of adverse events
Recruitment rate
+1 more
Secondary outcome measures
Montgomery-Åsberg Depression Rating Scale (MADRAS) Score 0-60 (Higher scores represent higher depression). Measure changes in symptoms of depression
Toronto Side Effects Scale (TSES) - 32 items (each item has a score 1-25; higher score means higher intensity). Measure adverse side effects from antidepressant treatment

SMILE Trial Design

2Treatment groups
Experimental Treatment
Active Control
Group I: Nitrous Oxide + saline solutionExperimental Treatment1 Intervention
Group II: Oxygen + MidazolamActive Control1 Intervention

Find a Location

Who is running the clinical trial?

Unity Health TorontoLead Sponsor
536 Previous Clinical Trials
447,489 Total Patients Enrolled
17 Trials studying Depression
3,075 Patients Enrolled for Depression
Karim LadhaLead Sponsor
1 Previous Clinical Trials
10 Total Patients Enrolled
1 Trials studying Depression
10 Patients Enrolled for Depression

Media Library

Nitrous Oxide 99 % (Other) Clinical Trial Eligibility Overview. Trial Name: NCT04957368 — Phase 4
Depression Research Study Groups: Nitrous Oxide + saline solution, Oxygen + Midazolam
Depression Clinical Trial 2023: Nitrous Oxide 99 % Highlights & Side Effects. Trial Name: NCT04957368 — Phase 4
Nitrous Oxide 99 % (Other) 2023 Treatment Timeline for Medical Study. Trial Name: NCT04957368 — Phase 4

Frequently Asked Questions

These questions and answers are submitted by anonymous patients, and have not been verified by our internal team.

Is this medical experiment open to minors?

"This trial is accepting volunteers aged between 18 and 65 years old."

Answered by AI

Have there been prior investigations into the efficacy of Nitrous Oxide 99 %?

"At this time, 76 trials related to Nitrous Oxide 99 % are running. Of those live studies, 11 have reached Phase 3 and the vast majority of these research initiatives are based in Saint Louis, Missouri; however there is a total of 735 sites participating."

Answered by AI

To whom is enrollment for this trial available?

"This study is seeking 40 volunteers suffering from psychosis in the 18-65 age range. In order to be eligible, individuals must exhibit moderate to severe depression as determined by the HAMD score and female participants of childbearing potential must utilize highly effective contraception or practice abstinence if that is their usual lifestyle choice."

Answered by AI

Is Nitrous Oxide 99 % risk-free for patients?

"The safety of nitrous oxide 99% is highly rated, garnering a 3 on the 1-3 scale due to it being approved with Phase 4 trials."

Answered by AI

What medical purposes does Nitrous Oxide 99 % typically serve?

"Nitrous Oxide 99% can effectively help patients manage preoperative sedation, analgesia, and anaesthesia therapy."

Answered by AI

Is this research endeavor currently accepting participants?

"Per the details on clinicaltrials.gov, this medical experiment is currently in its recruitment stage. This trial was uploaded to the platform on November 3rd 2021 and has recently been modified as of December 6th 2021."

Answered by AI

What is the aggregate of individuals who have signed up for this experiment?

"Affirmative. The evidence found on clinicaltrials.gov demonstrates that this experiment, first posted on November 3rd 2021, is actively seeking participants. 40 volunteers are needed from one medical centre to partake in the trial."

Answered by AI

Who else is applying?

How old are they?
18 - 65
What site did they apply to?
St. Michael's Hospital
What portion of applicants met pre-screening criteria?
Met criteria
Recent research and studies
clinicaltrials.govStudy
Sustained Mood Improvement With Laughing Gas Exposure: A Randomized Controlled Pilot Trial
Karim Ladha 2021. "Sustained Mood Improvement With Laughing Gas Exposure: A Randomized Controlled Pilot Trial". ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT04957368.
~12 spots leftby Apr 2025
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