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Trial details imported from ClinicalTrials.gov

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




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

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 - 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
Timepoint [1] 0 0
over 4 weeks from baseline
Secondary outcome [1] 0 0
Treatment response and remission - Treatment response (=50% reduction on HDRS-21) and remission (HDRS-21 =7 points), nitrous oxide vs. placebo
Timepoint [1] 0 0
at 24 hours
Secondary outcome [2] 0 0
Pattern of treatment response - Assessed using daily Profile of Mood States (POMS) scale, nitrous oxide vs. placebo
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
Timepoint [2] 0 0
daily over the first week after first treatment session
Secondary outcome [3] 0 0
Sustainability of treatment response - change in HDRS-21 scores - 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
Timepoint [3] 0 0
over 7 weeks
Secondary outcome [4] 0 0
Sustainability of treatment response - response and remission rates - Response and remission rates (%), nitrous oxide vs placebo
Timepoint [4] 0 0
over 7 weeks
Secondary outcome [5] 0 0
Treatment compliance rate - Refusal or inability to attend further treatments, nitrous oxide vs placebo
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 - 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.
Timepoint [6] 0 0
over 7 weeks
Secondary outcome [7] 0 0
Computerized Adaptive Test-Depression Inventory (CAT-DI) - 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.
Timepoint [7] 0 0
over 7 weeks
Secondary outcome [8] 0 0
Computerized Adaptive Test-Suicide Scale (CAT-SS) - 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.
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
Gender
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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
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
Other
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/show/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
c.deng@alfred.org.au
Contact person for scientific queries

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