Sustained Mood Improvement With Laughing Gas Exposure

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

120 participants

Study Classification

INTERVENTIONAL

Study Start Date

2026-02-01

Study Completion Date

2028-09-01

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

Multi-centre, parallel group, blinded, 1:1 randomized controlled trial to determine the effect of nitrous oxide on reducing symptoms of depression in patients with treatment resistant depression.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

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

NCT04957368

Treatment Resistant Depression Major Depressive Disorder

COMPLETED PHASE4

SMILE Trial - Imaging Sub-Study

NCT05528718

Major Depressive Disorder

COMPLETED

Antidepressant Effects of Nitrous Oxide

NCT05357040

Major Depressive Disorder Treatment Resistant Depression

RECRUITING PHASE2

Nitrous Oxide for Major Depressive Disorder

NCT03932825

Depressive Disorder Major Depressive Disorder Treatment Resistant Depression +2 more

COMPLETED PHASE2

Nitrous Oxide for Late-Life Depression - PROTO-BRAIN

NCT05007028

Late-Life Depression Resistant Depression, Treatment

COMPLETED NA

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

SMILE is a multi-centre, parallel-group, blinded randomized controlled trial of 120 patients with treatment resistant depression. Consented eligible patients will be randomized to 1) Inhalation of Nitrous Oxide + Intravenous Saline (intervention Group)or 2) Inhalation of Oxygen + Intravenous Midazolam (Active Control Group). Participants will receive their respective study intervention once a week for four weeks for a total of four sessions. Follow-up visits will be conducted over the phone 2-weeks, 4-weeks, and 12-weeks following the last intervention visit. Questionnaires will be administered to assess change in depressive symptoms, function, and quality of life.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Major Depressive Disorder Treatment Resistant Depression

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

This study will be a phase III, double-blind, randomized, active placebo-controlled, superiority trial with two parallel arms.

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Outcome Assessors

As noted above, only the individual administering the intervention will be aware of allocation assignment due to safety. The participant and outcomes assessors will be blinded to minimize bias.

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Intervention Group

Nitrous oxide+ intravenous Saline

Group Type EXPERIMENTAL

Inhalation of Nitrous oxide (Laughing gas) + intravenous saline

Intervention Type DRUG

Nitrous oxide at an inspiratory concentration of 50% with concurrent intravenous saline (20ml) for one hour.

Active Control Group

100% oxygen+ intravenous midazolam

Group Type ACTIVE_COMPARATOR

inhalation of %100 oxygen + intravenous midazolam

Intervention Type DRUG

Inspiration of 100% oxygen with concurrent intravenous midazolam (0.02mg/kg, up to 2 mg) for one hour.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Inhalation of Nitrous oxide (Laughing gas) + intravenous saline

Nitrous oxide at an inspiratory concentration of 50% with concurrent intravenous saline (20ml) for one hour.

Intervention Type DRUG

inhalation of %100 oxygen + intravenous midazolam

Inspiration of 100% oxygen with concurrent intravenous midazolam (0.02mg/kg, up to 2 mg) for one hour.

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Nitrous oxide Midazolam

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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 episodes, as defined by the Montgomery-Åsberg Depression Rating Scale (MADRS) \> 21
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 \> 4 on MADRS item 10
2. Diagnosis of 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. Known history of hypersensitivity or allergy to nitrous oxide, midazolam or any ingredients in the study formulations
7. Contraindication to receiving nitrous oxide (e.g. any condition where air is entrapped within a body and its expansion might be dangerous such as, pneumothorax, elevated intracranial pressure, air embolism, recent middle ear, vitreoretinal or bowel obstruction surgeries, etc.)
8. Known chronic cobalamin or folate deficiency (e.g. signs of anemia or neurological symptoms, with plasma levels of homocysteine over 15 µmol/L and abnormal red blood cells and leukocytes on a complete blood count CBC) or current methotrexate use
9. Contraindication to receiving the placebo midazolam (e.g. shock, chronic heart failure, chronic obstructive pulmonary disease, closed-angle glaucoma, renal failure, patients with limited pulmonary reserve or those with severe decline of vital signs)
10. Daily use of centrally acting medicinal products, such as opioid agonists, (e.g. naloxone and naltrexone) morphine derivatives (e.g. oxycodone, hydrocodone, oxymorphone, codeine), benzodiazepines (e.g. diazepam, clonazepam, alprazolam) and/or other central nervous system depressants such as barbiturates (e.g. phenobarbital, pentobarbital, amobarbital) and alcohol within the past week.
11. Pregnancy or breastfeeding
12. Received electroconvulsive therapy within the past six months
13. Received ketamine treatment within the past six months
14. Received repetitive transcranial magnetic stimulation within the past six months
15. Unwilling to maintain current antidepressant regimen.

Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No