Sustained Mood Improvement With Laughing Gas Exposure: A Randomized Controlled Double-Blind Trial
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 120
- 试验地点
- 5
- 主要终点
- Change in Montgomery-Åsberg Depression Rating Scale (MADRS) score
研究概览
简要总结
Multi-centre, parallel group, blinded, 1:1 randomized controlled trial to determine the effect of nitrous oxide on reducing symptoms of depression in patients with treatment resistant depression.
详细描述
SMILE is a multi-centre, parallel-group, blinded randomized controlled trial of 120 patients with treatment resistant depression. Consented eligible patients will be randomized to 1) Inhalation of Nitrous Oxide + Intravenous Saline (intervention Group)or 2) Inhalation of Oxygen + Intravenous Midazolam (Active Control Group). Participants will receive their respective study intervention once a week for four weeks for a total of four sessions. Follow-up visits will be conducted over the phone 2-weeks, 4-weeks, and 12-weeks following the last intervention visit. Questionnaires will be administered to assess change in depressive symptoms, function, and quality of life.
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
As noted above, only the individual administering the intervention will be aware of allocation assignment due to safety. The participant and outcomes assessors will be blinded to minimize bias.
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •18 to 65 years of age
- •Meeting Diagnostic and Statistical Manual for Mental Disorders (DSM-5) criteria for Major Depressive Disorder (MDD)
- •Current major depressive episode as confirmed by the Mini International Neuropsychiatric Interview (MINI) for DSM-5
- •Experiencing moderate to severe depressive episodes, as defined by the Montgomery-Åsberg Depression Rating Scale (MADRS) > 21
- •Failure of two trials of antidepressant therapy of adequate dose and duration, during the current depressive episode
- •For women of childbearing potential, use of highly effective or double-barrier methods of contraception. Abstinence is acceptable if it is the preferred and usual lifestyle of the female participant
- •Capacity to provide informed consent.
排除标准
- •Acute suicidality defined as score > 4 on MADRS item 10
- •Diagnosis of Bipolar Disorder
- •Current substance abuse or dependence and/or history of alcohol abuse or dependence within the past year
- •Current or lifetime history of schizophrenia or schizoaffective disorder
- •Known history of hypersensitivity or allergy to nitrous oxide, midazolam or any ingredients in the study formulations
- •Contraindication to receiving nitrous oxide (e.g. any condition where air is entrapped within a body and its expansion might be dangerous such as, pneumothorax, elevated intracranial pressure, air embolism, recent middle ear, vitreoretinal or bowel obstruction surgeries, etc.)
- •Known chronic cobalamin or folate deficiency (e.g. signs of anemia or neurological symptoms, with plasma levels of homocysteine over 15 µmol/L and abnormal red blood cells and leukocytes on a complete blood count CBC) or current methotrexate use
- •Contraindication to receiving the placebo midazolam (e.g. shock, chronic heart failure, chronic obstructive pulmonary disease, closed-angle glaucoma, renal failure, patients with limited pulmonary reserve or those with severe decline of vital signs)
- •Daily use of centrally acting medicinal products, such as opioid agonists, (e.g. naloxone and naltrexone) morphine derivatives (e.g. oxycodone, hydrocodone, oxymorphone, codeine), benzodiazepines (e.g. diazepam, clonazepam, alprazolam) and/or other central nervous system depressants such as barbiturates (e.g. phenobarbital, pentobarbital, amobarbital) and alcohol within the past week.
- •Pregnancy or breastfeeding
- •Received electroconvulsive therapy within the past six months
- •Received ketamine treatment within the past six months
- •Received repetitive transcranial magnetic stimulation within the past six months
- •Unwilling to maintain current antidepressant regimen.
研究组 & 干预措施
Intervention Group
Nitrous oxide+ intravenous Saline
干预措施: Inhalation of Nitrous oxide (Laughing gas) + intravenous saline (Drug)
Active Control Group
100% oxygen+ intravenous midazolam
干预措施: inhalation of %100 oxygen + intravenous midazolam (Drug)
结局指标
主要结局
Change in Montgomery-Åsberg Depression Rating Scale (MADRS) score
时间窗: Baseline to the 2-week follow-up (Visit 6 - Day 35).
The MADRS is a 10-item clinician-rated scale used to assess the severity of depressive symptoms and to detect changes over time in response to treatment. It is commonly used in randomized controlled trials due to its sensitivity to change and strong psychometric properties. The MADRS is also recognized by regulatory and health technology assessment agencies, including the U.S. Food and Drug Administration (FDA) and the Canadian Agency for Drugs and Technologies in Health (CADTH), as an established measure for evaluating treatment efficacy in depression. Higher scores indicate worse outcomes and greater severity of depression.
次要结局
- Proportion of patients who achieved a response(2-week and 12-week follow-ups post last intervention visit)
- Proportion of patients who achieved remission(2-week and 12-week follow-ups post last intervention visit)
- Change in self-reported depressive symptoms(2-week and 12-week follow-ups post last intervention visit)
- Change in cognitive function(2-week and 12-week follow-ups post last intervention visit)
- Change in functioning and disability(2-week and 12-week follow-ups post last intervention visit)
- Change in anxiety symptoms(2-week and 12-week follow-ups post last intervention visit)
- Change in quality of life(2-week and 12-week follow-ups post last intervention visit)
- Assessment of Safety via FIBSER Scale(Baseline to Week 12)
研究者
Karim Ladha
MD MSc FRCPC
Women's College Hospital