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

Major Depressive Disorder Clinical Trial

— SMILE  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04957368
• Other study ID #: 21-096
• Status: Active, not recruiting
• Phase: Phase 4
• Start date: November 3, 2021
• Est. completion date: February 27, 2024

Study information

• Verified date: January 2024
• Source: Unity Health Toronto
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 40
• Est. completion date: February 27, 2024
• Est. primary completion date: January 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. 18 to 65 years of age

2. Meeting Diagnostic and Statistical Manual for Mental Disorders (DSM-5) criteria for Major Depressive Disorder (MDD)

3. Current major depressive episode as confirmed by the Mini International Neuropsychiatric Interview (MINI) for DSM-5

4. Experiencing moderate to severe depressive episode, as defined by the Hamilton Depression Rating Scale (HAMD)>17

5. Failure of two trials of antidepressant therapy of adequate dose and duration, during the current depressive episode

6. 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

7. Capacity to provide informed consent. Exclusion criteria

1. Acute suicidality defined as score =3 on HAMD item 3

2. Major Depressive Episode in people with Bipolar Disorder

3. Current substance abuse or dependence and/or history of alcohol abuse or dependence within the past year

4. Dementia

5. Current or lifetime history of schizophrenia or schizoaffective disorder

6. Current history of dissociative disorders

7. Known history of hypersensitivity or allergy to Nitrous Oxide, Midazolam or any ingredients in the study formulations

8. Contraindication to receiving nitrous oxide

9. Chronic cobalamin or folate deficiency

10. Contraindication to receiving the placebo midazolam

11. 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

12. Pregnancy or breastfeeding in female participants

13. Electroconvulsive therapy within the current depressive episode

14. Receiving ketamine treatment within the current depressive episode

15. Unwilling to maintain current antidepressant regimen.

Related Conditions & MeSH terms

• Depressive Disorder
• Depressive Disorder, Major
• Depressive Disorder, Treatment-Resistant
• Major Depressive Disorder
• Treatment Resistant Depression

Intervention

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

Locations

Country	Name	City	State
Canada	St. Michael's Hospital	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
Unity Health Toronto

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Recruitment rate	Recruitment rate	2 Years
Primary	Withdrawal rate		2 Years
Primary	Adherence rate	Feasibility	2 Years
Primary	Frequency of adverse events	Safety and tolerability	2 Years
Secondary	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
Secondary	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