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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
Titles & IDs
Public title
Nitrous Oxide for the Treatment of Major Depressive Disorder
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Scientific title
Evaluation of the Antidepressant Effects of Nitrous Oxide in People With Major Depressive Disorder
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Secondary ID [1]
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438/19
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Depression
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Major Depressive Disorder
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Condition category
Condition code
Mental Health
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Depression
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Intervention/exposure
Study type
Interventional
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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.
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Change in HDRS-21 score
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Assessment method [1]
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21-point Hamilton Depression Rating Scale
Interview-based questionnaire used to measure the severity of depression. Consists of 21 items with a score calculated from the first 17 answers. Higher scores are associated with more severe depression:
0 - 7 = Normal 8 - 13 = Mild Depression 14-18 = Moderate Depression 19 - 22 = Severe Depression \> 23 = Very Severe Depression Max score = 52
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Timepoint [1]
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over 4 weeks from baseline
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Secondary outcome [1]
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Treatment response and remission
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Assessment method [1]
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Treatment response (=50% reduction on HDRS-21) and remission (HDRS-21 =7 points), nitrous oxide vs. placebo
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Timepoint [1]
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at 24 hours
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Secondary outcome [2]
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Pattern of treatment response
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Assessment method [2]
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Assessed using daily Profile of Mood States scale. The POMS measures six different dimensions of mood swings over a period of time. score range with lower scores indicative of people with more stable mood profiles The Profile of Mood States (POMS) questionnaire is a validated psychological test containing 65 emotions/ mood states. Participants are asked to rank their current mood states using the scale 'not at all', 'a little', 'moderately', 'quite a lot' or 'extremely'. Total Mood Disturbance (TMD) score and an analysis of tension, depression, anger, vigour, fatigue and confusion is performed based on the participants mood states. Total Mood Disturbance (TMD) can be calculated by adding the scores for Tension, Depression, Anger, Fatigue and Confusion and then subtracting the score for Vigour.
• TMD = (Tension + Depression + Anger + Fatigue + Confusion) - Vigour
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Timepoint [2]
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Up to 1 week after treatment
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Secondary outcome [3]
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Sustainability of treatment response - change in HDRS-21 scores
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Assessment method [3]
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Change in the HDRS-21 score, nitrous oxide vs placebo
HDRS-21 is an interview-based questionnaire used to measure the severity of depression. Consists of 21 items with a score calculated from the first 17 answers. Higher scores are associated with more severe depression:
0 - 7 = Normal 8 - 13 = Mild Depression 14-18 = Moderate Depression 19 - 22 = Severe Depression \> 23 = Very Severe Depression Max score = 52
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Timepoint [3]
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over 7 weeks
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Secondary outcome [4]
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Sustainability of treatment response - response and remission rates
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Assessment method [4]
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Response and remission rates (%), nitrous oxide vs placebo
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Timepoint [4]
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over 7 weeks
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Secondary outcome [5]
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Treatment compliance rate
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Assessment method [5]
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Refusal or inability to attend further treatments, nitrous oxide vs placebo
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Timepoint [5]
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over 4 weeks
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Secondary outcome [6]
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Dose effect of nitrous oxide using treatment-by-dose interaction term in a logistic regression model
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Assessment method [6]
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Dose effect of nitrous oxide at 25% and 50% using a treatment-by-dose (group) interaction term in a logistic regression model to assess for statistical significance.
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Timepoint [6]
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over 7 weeks
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Secondary outcome [7]
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Computerized Adaptive Test-Depression Inventory (CAT-DI)
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Assessment method [7]
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Adaptive testing questionnaire that assesses severity, likelihood and percentile of depression based on an average of 12 items administered from a question bank of 400 items. Questions are adapted to the participants answers and targeted to their level of impairment. Results generate include: severity of depression (normal, mild, moderate, severe), likelihood of depression (out of probability of 1), percentile of severity.
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Timepoint [7]
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over 7 weeks
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Secondary outcome [8]
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Computerized Adaptive Test-Suicide Scale (CAT-SS)
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Assessment method [8]
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Adaptive testing questionnaire that assesses risk and severity of suicide based on items administered from a question bank. Questions are adapted to the participants answers and targeted to their level of impairment. Results generate include: risk of suicide (low, intermediate, high) and a percentile of risk.
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Timepoint [8]
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over 7 weeks
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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
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Minimum age
18
Years
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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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).
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Blinded (masking used)
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Who is / are masked / blinded?
The people receiving the treatment/s
The people assessing the outcomes
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 2
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Recruiting
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
22/01/2019
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
10/12/2023
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Actual
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Sample size
Target
172
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Accrual to date
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Final
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Recruitment in Australia
Recruitment state(s)
VIC
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Recruitment hospital [1]
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Alfred Hospital - Melbourne
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Recruitment postcode(s) [1]
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3004 - Melbourne
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Recruitment outside Australia
Country [1]
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United States of America
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State/province [1]
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Illinois
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Funding & Sponsors
Primary sponsor type
Government body
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Name
Bayside Health
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Address
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Country
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Ethics approval
Ethics application status
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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.
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Trial website
https://clinicaltrials.gov/study/NCT03869736
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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Paul Myles, MD
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Address
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The Alfred
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Country
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Phone
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Fax
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Email
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Contact person for public queries
Name
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Carolyn Deng, MBChB
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Address
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Country
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Phone
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+61399030760
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Fax
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Email
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[email protected]
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Contact person for scientific queries
Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
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No/undecided IPD sharing reason/comment
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What supporting documents are/will be available?
No Supporting Document Provided
Results publications and other study-related documents
No documents have been uploaded by study researchers.
Results not provided in
https://clinicaltrials.gov/study/NCT03869736