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

Primary Purpose

Treatment Resistant Depression, Major Depressive Disorder

Status

Recruiting

Phase

Phase 4

Locations

Canada

Study Type

Interventional

Intervention

Nitrous Oxide 99 %

Oxygen + Midazolam

About this trial

This is an interventional other trial for Treatment Resistant Depression focused on measuring Feasibility trial, Nitrous Oxide

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

St. Michael's HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Nitrous Oxide + saline solution

Oxygen + Midazolam

Arm Description

Outcomes

Primary Outcome Measures

Recruitment rate

Withdrawal rate

Adherence rate

Feasibility

Frequency of adverse events

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

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

Frequencies of safety and tolerability

Full Information

NCT ID

NCT04957368

First Posted

April 26, 2021

Last Updated

December 8, 2022

Sponsor

Karim Ladha

Collaborators

Unity Health Toronto

1. Study Identification

Unique Protocol Identification Number

NCT04957368

Brief Title

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

Acronym

SMILE

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

December 2022

Overall Recruitment Status

Recruiting

Study Start Date

November 3, 2021 (Actual)

Primary Completion Date

August 2023 (Anticipated)

Study Completion Date

October 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Karim Ladha

Collaborators

Unity Health Toronto

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Treatment Resistant Depression, Major Depressive Disorder

Keywords

Feasibility trial, Nitrous Oxide

7. Study Design

Primary Purpose

Other

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Nitrous Oxide + saline solution

Arm Type

Experimental

Arm Title

Oxygen + Midazolam

Arm Type

Active Comparator

Intervention Type

Drug

Intervention Name(s)

Nitrous Oxide 99 %

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Oxygen + Midazolam

Intervention Description

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

Primary Outcome Measure Information:

Title

Recruitment rate

Description

Recruitment rate

Time Frame

2 Years

Title

Withdrawal rate

Time Frame

2 Years

Title

Adherence rate

Description

Feasibility

Time Frame

2 Years

Title

Frequency of adverse events

Description

Safety and tolerability

Time Frame

2 Years

Secondary Outcome Measure Information:

Title

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

Description

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

Time Frame

6 weeks

Title

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

Description

Frequencies of safety and tolerability

Time Frame

6 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Karim Ladha, MD

Phone

416-864-5825

karim.ladha@mail.utoronto.ca

First Name & Middle Initial & Last Name or Official Title & Degree

Janneth Pazmino-Canizares, MSc

Phone

416-864-6060

Ext

49561

Janneth.Pazmino-Canizares@unityhealth.to

Facility Information:

Facility Name

St. Michael's Hospital

City

Toronto

State/Province

Ontario

ZIP/Postal Code

M5B 1W8

Country

Canada

Individual Site Status

Recruiting

12. IPD Sharing Statement

Plan to Share IPD

IPD Sharing Plan Description

No individual participant data has been planned to be shared with other researchers at this point since this is a feasibility study with only 40 participants

Learn more about this trial

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

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