Evaluation of the Antidepressant Effects of Nitrous Oxide in People With Major Depressive Disorder
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 入组人数
- 172
- 试验地点
- 2
- 主要终点
- Change in HDRS-21 score
研究概览
简要总结
To evaluate the acute and sustained antidepressant effects of nitrous oxide in people with major depressive disorder; and further evaluate these effects by identifying the optimal dose and regimen to guide current practice, and to plan a future large pragmatic trial.
详细描述
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 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 session 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% or 25% nitrous oxide. Depression severity and outcomes related to treatment responses will be continuously assessed by a 'blinded-to-randomization' psychiatry (MD) rater at weekly intervals during study patient participation, using validated psychiatric diagnostics (Hamilton Depression Rating Scale-21 [HDRS-21 or HAM-D]; Profile of Mood States [POMS]; Computerized Adaptive Test-Mental Health [CAT-MH]; Sheehan-STS [S-STS]; Visual Analog Scale [VAS]).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Outcomes Assessor)
盲法说明
Patient and assessor blinded to study group assigned.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Adult (≥18 years, both sexes)
- •DSM-5 criteria for MDD without psychosis, as determined using a structured clinical interview [Mini International Neuropsychiatric Interview], MDD, defined by a pre-treatment score >16 on the HDRS-21 scale and meeting DSM-5 for MDD
排除标准
- •A current or past history of bipolar disorder, schizophrenia, or schizoaffective disorder.
- •Current obsessive-compulsive disorder, panic disorder, or documented Axis II diagnoses
- •Active suicidal intention, as determined by clinical interview assessment tool (Sheehan-STS) and clinical examination
- •Active or recent (<12 months) substance use disorder; excluding nicotine
- •Administration of NMDA-antagonists (e.g., ketamine) in previous 3 months
- •Ongoing treatment with ECT
- •Presence of acute medical illness that could interfere with study participation, including significant pulmonary disease
- •Pregnancy or breastfeeding
- •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).
研究组 & 干预措施
Treatment; Nitrous Oxide 50% or 25%, group
Four-weekly, 60-minute inhalation sessions of 25% or 50% nitrous oxide, randomly assigned.
干预措施: Nitrous oxide gas for inhalation (Drug)
Control; Oxygen-air mixture, group
Four-weekly, 60-minute inhalation sessions of an oxygen and air mixture.
干预措施: Placebo (Drug)
结局指标
主要结局
Change in HDRS-21 score
时间窗: Over 4-weeks from baseline
Monitor changes in Hamilton Depression Rating Scale-21 (HDRS-21) scores to determine whether a series of four, 60-minute sessions of inhaled nitrous oxide vs placebo (once-per-week) has significant antidepressant activity. The HDRS-21 is an interview-based psychiatric diagnostic used to evaluate depression severity. Scores are calculated by using the first 17 responses of this 21 item questionnaire. 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
次要结局
- Treatment response(At 24-hours (following treatment-1))
- Changes in 'Profile of Mood States' scores(Up to 1-week (following treatment-1))
- Sustainability of treatment response(Over 7-weeks (length of study participation).)
- Treatment dose response comparison(Over 7-weeks (length of study participation))
- Treatment cycle compliance(Over 4-weeks (weekly treatment sessions))
- Changes in Computerize Adaptive Testing - Mental Health (CAT-MH) 'depression' scores(Over 7-weeks (length of study participation) from Baseline)
- Changes in Computerize Adaptive Testing - Mental Health (CAT-MH) 'anxiety' scores(Over 7-weeks (length of study participation) from Baseline)
- Changes in Computerize Adaptive Testing - Mental Health (CAT-MH) 'suicide' scores(Over 7-weeks (length of study participation) from Baseline)
- Suicidal ideation tracking(Over 7-weeks (length of study participation) from Baseline)
- Visual Analog Scale (VAS)(At Baseline (Prior to treatment-1))
- Treatment remission(At 24-hours (following treatment-1))
- Treatment response(At 24-hours (following treatment-1))
- Changes in 'Profile of Mood States' scores(Up to 1-week (following treatment-1))
- Sustainability of treatment response(Over 7-weeks (length of study participation).)
- Treatment dose response comparison(Over 7-weeks (length of study participation))
- Treatment cycle compliance(Over 4-weeks (weekly treatment sessions))
- Changes in Computerize Adaptive Testing - Mental Health (CAT-MH) 'depression' scores(Over 7-weeks (length of study participation) from Baseline)
- Changes in Computerize Adaptive Testing - Mental Health (CAT-MH) 'suicide' scores(Over 7-weeks (length of study participation) from Baseline)
- Changes in Computerize Adaptive Testing - Mental Health (CAT-MH) 'anxiety' scores(Over 7-weeks (length of study participation) from Baseline)
- Suicidal ideation tracking(Over 7-weeks (length of study participation) from Baseline)
- Visual Analog Scale (VAS)(At Baseline (Prior to treatment-1))
- Treatment remission(At 24-hours (following treatment-1))