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Nitrous Oxide for the Treatment of Major Depressive Disorder

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03869736
Recruitment Status : Unknown
Verified April 2020 by Bayside Health.
Recruitment status was:  Recruiting
First Posted : March 11, 2019
Last Update Posted : April 22, 2020
Sponsor:
Information provided by (Responsible Party):
Bayside Health

Tracking Information
First Submitted Date  ICMJE December 16, 2018
First Posted Date  ICMJE March 11, 2019
Last Update Posted Date April 22, 2020
Actual Study Start Date  ICMJE January 22, 2019
Estimated Primary Completion Date December 10, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 7, 2019)
Change in HDRS-21 score [ Time Frame: over 4 weeks from baseline ]
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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 20, 2020)
  • Treatment response and remission [ Time Frame: at 24 hours ]
    Treatment response (≥50% reduction on HDRS-21) and remission (HDRS-21 ≤7 points), nitrous oxide vs. placebo
  • Pattern of treatment response [ Time Frame: Up to 1 week after treatment ]
    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
  • Sustainability of treatment response - change in HDRS-21 scores [ Time Frame: over 7 weeks ]
    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
  • Sustainability of treatment response - response and remission rates [ Time Frame: over 7 weeks ]
    Response and remission rates (%), nitrous oxide vs placebo
  • Treatment compliance rate [ Time Frame: over 4 weeks ]
    Refusal or inability to attend further treatments, nitrous oxide vs placebo
  • Dose effect of nitrous oxide using treatment-by-dose interaction term in a logistic regression model [ Time Frame: over 7 weeks ]
    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.
  • Computerized Adaptive Test-Depression Inventory (CAT-DI) [ Time Frame: over 7 weeks ]
    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.
  • Computerized Adaptive Test-Suicide Scale (CAT-SS) [ Time Frame: over 7 weeks ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 7, 2019)
  • Treatment response and remission [ Time Frame: at 24 hours ]
    Treatment response (≥50% reduction on HDRS-21) and remission (HDRS-21 ≤7 points), nitrous oxide vs. placebo
  • Pattern of treatment response [ Time Frame: daily over the first week after first treatment session ]
    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
  • Sustainability of treatment response - change in HDRS-21 scores [ Time Frame: over 7 weeks ]
    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
  • Sustainability of treatment response - response and remission rates [ Time Frame: over 7 weeks ]
    Response and remission rates (%), nitrous oxide vs placebo
  • Treatment compliance rate [ Time Frame: over 4 weeks ]
    Refusal or inability to attend further treatments, nitrous oxide vs placebo
  • Dose effect of nitrous oxide using treatment-by-dose interaction term in a logistic regression model [ Time Frame: over 7 weeks ]
    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.
  • Computerized Adaptive Test-Depression Inventory (CAT-DI) [ Time Frame: over 7 weeks ]
    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.
  • Computerized Adaptive Test-Suicide Scale (CAT-SS) [ Time Frame: over 7 weeks ]
    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.
Current Other Pre-specified Outcome Measures
 (submitted: March 7, 2019)
Adverse events [ Time Frame: over 7 weeks ]
Psychiatric AEs, such as new suicidal ideation and psychotic symptoms Other AEs, such as cardiorespiratory AEs or nausea and vomiting
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Nitrous Oxide for the Treatment of Major Depressive Disorder
Official Title  ICMJE Evaluation of the Antidepressant Effects of Nitrous Oxide in People With Major Depressive Disorder
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Depression
  • Major Depressive Disorder
Intervention  ICMJE
  • Drug: Nitrous Oxide
    1-hour sessions of inhaled nitrous oxide at concentrations of 25% or 50% (randomly assigned) to be administered weekly for 4 weeks.
  • Drug: Placebo
    1-hour sessions of inhaled oxygen-air mixture (inspired oxygen concentration ~23-30%) to be administered weekly for 4 weeks.
Study Arms  ICMJE
  • Experimental: Nitrous Oxide 50% or 25%
    Nitrous oxide at an inhaled concentration of 50% or 25%
    Intervention: Drug: Nitrous Oxide
  • Sham Comparator: Placebo
    Oxygen-air mixture
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: March 7, 2019)
172
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 10, 2020
Estimated Primary Completion Date December 10, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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

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).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03869736
Other Study ID Numbers  ICMJE 438/19
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Bayside Health
Study Sponsor  ICMJE Bayside Health
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Paul Myles, MD The Alfred
PRS Account Bayside Health
Verification Date April 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP