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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03869736




Registration number
NCT03869736
Ethics application status
Date submitted
16/12/2018
Date registered
11/03/2019
Date last updated
11/01/2023

Titles & IDs
Public title
Nitrous Oxide for the Treatment of Major Depressive Disorder
Scientific title
Evaluation of the Antidepressant Effects of Nitrous Oxide in People With Major Depressive Disorder
Secondary ID [1] 0 0
438/19
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Depression 0 0
Major Depressive Disorder 0 0
Condition category
Condition code
Mental Health 0 0 0 0
Depression

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Nitrous Oxide
Treatment: Drugs - Placebo

Experimental: Nitrous Oxide 50% or 25% - Nitrous oxide at an inhaled concentration of 50% or 25%

Sham comparator: Placebo - Oxygen-air mixture


Treatment: Drugs: Nitrous Oxide
1-hour sessions of inhaled nitrous oxide at concentrations of 25% or 50% (randomly assigned) to be administered weekly for 4 weeks.

Treatment: Drugs: Placebo
1-hour sessions of inhaled oxygen-air mixture (inspired oxygen concentration \~23-30%) to be administered weekly for 4 weeks.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change in HDRS-21 score
Timepoint [1] 0 0
over 4 weeks from baseline
Secondary outcome [1] 0 0
Treatment response and remission
Timepoint [1] 0 0
at 24 hours
Secondary outcome [2] 0 0
Pattern of treatment response
Timepoint [2] 0 0
Up to 1 week after treatment
Secondary outcome [3] 0 0
Sustainability of treatment response - change in HDRS-21 scores
Timepoint [3] 0 0
over 7 weeks
Secondary outcome [4] 0 0
Sustainability of treatment response - response and remission rates
Timepoint [4] 0 0
over 7 weeks
Secondary outcome [5] 0 0
Treatment compliance rate
Timepoint [5] 0 0
over 4 weeks
Secondary outcome [6] 0 0
Dose effect of nitrous oxide using treatment-by-dose interaction term in a logistic regression model
Timepoint [6] 0 0
over 7 weeks
Secondary outcome [7] 0 0
Computerized Adaptive Test-Depression Inventory (CAT-DI)
Timepoint [7] 0 0
over 7 weeks
Secondary outcome [8] 0 0
Computerized Adaptive Test-Suicide Scale (CAT-SS)
Timepoint [8] 0 0
over 7 weeks

Eligibility
Key inclusion criteria
1. Adult (=18 years, both sexes), with DSM-IV-TR criteria for MDD without psychosis, as determined using a structured clinical interview [Mini International Neuropsychiatric Interview]
2. MDD, as defined by a pretreatment score >18 on the HDRS-21 scale
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. A history of bipolar disorder, schizophrenia, schizoaffective disorder, obsessive-compulsive disorder, panic disorder, or documented Axis II diagnoses; active suicidal intention, as determined by clinical interview
2. Active or recent (<12 months) substance abuse or dependence; excluding nicotine
3. Administration of NMDA-antagonists (e.g., ketamine) in previous 3 months
4. Ongoing treatment with ECT
5. Presence of acute medical illness that could interfere with study participation, including significant pulmonary disease
6. Pregnancy or breastfeeding
7. Any contraindications to the use of nitrous oxide (e.g., pneumothorax, middle ear occlusion, elevated intracranial pressure, chronic cobalamin or folate deficiency unless treated with folic acid or vitamin B12).

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
22/01/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
10/12/2023
Actual
Sample size
Target
172
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Alfred Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
3004 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Illinois

Funding & Sponsors
Primary sponsor type
Government body
Name
Bayside Health
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The investigators are conducting a randomized controlled trial to evaluate the antidepressant effects of nitrous oxide in people with Major Depressive Disorder (MDD). MDD is a global medical condition that causes significant health and economic burden. Recent studies have shown that a single dose of ketamine, an NMDA-antagonist, has fast and long lasting anti-depressant effect. Nitrous oxide, another NMDA-antagonist, is widely used for anesthesia and analgesia, safer to administer and has fewer side effects than ketamine.

A randomized controlled crossover feasibility study showed significant reduction in depressive symptoms at 2 and 24 hours after a single 1-hour treatment session of inhaled nitrous oxide compared with placebo. Nitrous oxide is inexpensive and can be safely administered by any trained clinician. If found to be efficacious, it could be used to provide rapid anti-depressant effect whilst the benefit of traditional anti-depressants has its delayed effect. Another potential application could be in acutely suicidal patients.

This investigated-initiated phase 2b trial will enable confirmation and extension of the findings from the feasibility study, and identify the optimal dose and regimen in a broader population of those with MDD. Participants will be randomized to receive a weekly 1-hour inhalational sessions of either nitrous oxide or placebo (oxygen-air mixture) for 4 weeks, and the nitrous group will be further randomly assigned to a dose of 50% nitrous oxide or 25% nitrous oxide. Depression severity will be assessed by a blinded observer pre-treatment and at weekly intervals during and for 4 weeks after treatment using the Hamilton Depression Rating Scale.
Trial website
https://clinicaltrials.gov/study/NCT03869736
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Paul Myles, MD
Address 0 0
The Alfred
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Carolyn Deng, MBChB
Address 0 0
Country 0 0
Phone 0 0
+61399030760
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT03869736