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

Sponsor

Karim Ladha (Other)

Overall Status

Recruiting

CT.gov ID

NCT04957368

Collaborator

Unity Health Toronto (Other)

Enrollment

Location

Arms

22.9

Anticipated Duration (Months)

1.7

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Treatment Resistant Depression Major Depressive Disorder	Drug: Nitrous Oxide 99 % Drug: Oxygen + Midazolam	Phase 4

Study Design

Study Type:

Interventional

Anticipated Enrollment :

40 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Other

Official Title:

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

Actual Study Start Date :

Nov 3, 2021

Anticipated Primary Completion Date :

Aug 1, 2023

Anticipated Study Completion Date :

Oct 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Nitrous Oxide + saline solution	Drug: Nitrous Oxide 99 % Nitrous oxide will be administered at an inspiratory concentration of 50% with concurrent intravenous saline (100ml) for one hour.
Active Comparator: Oxygen + Midazolam	Drug: Oxygen + Midazolam Oxygen will be administered at 50% with intravenous midazolam (0.02mg/kg in 100ml) for one hour

Arm

Intervention/Treatment

Experimental: Nitrous Oxide + saline solution

Drug: Nitrous Oxide 99 %

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

Active Comparator: Oxygen + Midazolam

Drug: Oxygen + Midazolam

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

Outcome Measures

Primary Outcome Measures

Recruitment rate [2 Years]
Recruitment rate
Withdrawal rate [2 Years]
Adherence rate [2 Years]
Feasibility
Frequency of adverse events [2 Years]
Safety and tolerability

Secondary Outcome Measures

Montgomery-Åsberg Depression Rating Scale (MADRAS) Score 0-60 (Higher scores represent higher depression). Measure changes in symptoms of depression [6 weeks]
Frequencies on numbers of 1.- Remissions (defined as MADRS score < 10), 2.- Responses (defined as ≥ 50% reduction in MADRS score from baseline) 3.- No Responses
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]
Frequencies of safety and tolerability

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

18 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.

Exclusion criteria

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.