Sustained Mood Improvement With Laughing Gas Exposure: A Randomized Controlled Pilot Trial

NCT04957368 | Completed Phase 4

• 1 other identifier: 21-096
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to investigate a short-term treatment option for major depressive disorders by administering nitrous oxide gas. At this time, the main purpose is to complete a feasibility study with 40 participants suffering from treatment-resistant depression. Participants will be randomized to (1) Study group: Nitrous oxide (inhaled) + solution of saline (injected) and the (2) Control group: Oxygen (inhaled) + Midazolam (injected) as an Active Placebo.

Conditions

Treatment Resistant Depression; Major Depressive Disorder

Keywords

Feasibility trial; Nitrous Oxide

Outcome Measures

Primary Outcomes (4)

• Recruitment rate

  Recruitment rate

  2 Years

• Withdrawal rate

  2 Years

• Adherence rate

  Feasibility

  2 Years

• Frequency of adverse events

  Safety and tolerability

  2 Years

Secondary Outcomes (2)

• Montgomery-Åsberg Depression Rating Scale (MADRAS) Score 0-60 (Higher scores represent higher depression). Measure changes in symptoms of depression

  6 weeks

• 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

  6 weeks

Study Arms (2)

Nitrous Oxide + saline solution

EXPERIMENTAL

Drug: Nitrous Oxide 99 %

Oxygen + Midazolam

ACTIVE COMPARATOR

Drug: Oxygen + Midazolam

Interventions

Nitrous Oxide 99 % DRUG

Nitrous oxide will be administered at an inspiratory concentration of 50% with concurrent intravenous saline (100ml) for one hour.

Nitrous Oxide + saline solution

Oxygen + Midazolam DRUG

Oxygen will be administered at 50% with intravenous midazolam (0.02mg/kg in 100ml) for one hour

Oxygen + Midazolam

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• to 65 years of age
• Meeting Diagnostic and Statistical Manual for Mental Disorders (DSM-5) criteria for Major Depressive Disorder (MDD)
• Current major depressive episode as confirmed by the Mini International Neuropsychiatric Interview (MINI) for DSM-5
• Experiencing moderate to severe depressive episode, as defined by the Hamilton Depression Rating Scale (HAMD)\>17
• Failure of two trials of antidepressant therapy of adequate dose and duration, during the current depressive episode
• For women of childbearing potential, use of highly effective or double-barrier methods of contraception. Abstinence is acceptable if it is the preferred and usual lifestyle of the female participant
• Capacity to provide informed consent.

You may not qualify if:

• Acute suicidality defined as score ≥3 on HAMD item 3
• Major Depressive Episode in people with Bipolar Disorder
• Current substance abuse or dependence and/or history of alcohol abuse or dependence within the past year
• Dementia
• Current or lifetime history of schizophrenia or schizoaffective disorder
• Current history of dissociative disorders
• Known history of hypersensitivity or allergy to Nitrous Oxide, Midazolam or any ingredients in the study formulations
• Contraindication to receiving nitrous oxide
• Chronic cobalamin or folate deficiency
• Contraindication to receiving the placebo midazolam
• Use of centrally acting medicinal products, such as opioid agonists, morphine derivatives, benzodiazepines and/or other central nervous system depressants such as barbiturates and alcohol
• Pregnancy or breastfeeding in female participants
• Electroconvulsive therapy within the current depressive episode
• Receiving ketamine treatment within the current depressive episode
• Unwilling to maintain current antidepressant regimen.

Sponsors & Collaborators

• Unity Health Toronto: lead

Study Sites (1)

St. Michael's Hospital

Toronto, Ontario, M5B 1W8, Canada

Location

Related Publications (1)

• Ladha KS, Lee J, Mattina GF, Pazmino-Canizares J, Wijeysundera DN, Gholamali Nezhad F, Philip K, Tassone VK, Adamsahib F, Bhat V; SMILE Study Investigators. Sustained Mood Improvement with Laughing Gas Exposure (SMILE): Study protocol for a randomized placebo-controlled pilot trial of nitrous oxide for treatment-resistant depression. PLoS One. 2024 Jan 19;19(1):e0297330. doi: 10.1371/journal.pone.0297330. eCollection 2024.

  PMID: 38241247 DERIVED

MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant; Depressive Disorder, Major

Interventions

Oxygen; Midazolam

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Chalcogens; Elements; Inorganic Chemicals; Gases; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 26, 2021
• First Posted: July 12, 2021
• Study Start: November 3, 2021
• Primary Completion: February 27, 2024
• Study Completion: February 27, 2024
• Last Updated: May 8, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)