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

Study Overview
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Brief Summary
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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.

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

Conditions
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Treatment Resistant Depression, Major Depressive Disorder

Intervention / Treatment
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* Drug: Nitrous Oxide 99 %
* Drug: Oxygen + Midazolam


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Montgomery-Åsberg Depression Rating Scale (MADRAS) Score 0-60 (Higher scores represent higher depression). Measure changes in symptoms of depression | 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 | 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 | Frequencies of safety and tolerability | 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Feasibility trial, Nitrous Oxide