Nitrous Oxide as a Putative Novel Dual-Mechanism Treatment for Bipolar Disorder
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 25
- 试验地点
- 1
- 主要终点
- Change in Montgomery-Asberg Depression Scale (MADRS) score
研究概览
简要总结
This study is a 7-day randomized, double-blind proof-of-concept pilot study of nitrous oxide vs. midazolam in 40 adults (20-60 years) with bipolar disorder (BD) (type I or II). Ongoing pharmacological and psychosocial treatments may continue, provided that they have not been initiated or significantly modified in the preceding 2 weeks. Participants' current treatment as prescribed by clinical psychiatrists will not be modified or interfered in this study. The study involves 3 visits. During study visit 1, participants will complete screening to ensure study eligibility. This will be done using interview measures. During study visit 2, participants will complete anthropomorphic measurements, measurement of endothelial function, screening blood work, ECGs, and an anaesthesia screener. During study visit 3, participants will receive the treatment (nitrous oxide or midazolam), complete an MRI scan, and complete interview measures and self-reports. There will be anthropomorphic measurements taken as well. The participant will be required to complete phone interviews and self-reports over the subsequent 7 days. There are 4 main predictions: 1. Nitrous oxide will significantly reduce depression symptoms vs. midazolam. 2. Nitrous oxide will significantly increase frontal cortical perfusion vs. midazolam. 3. Lower perfusion in frontal cortical regions at baseline will be associated with greater improvement in depression symptoms following nitrous oxide treatment. 4. Poorer endothelial function will be associated with greater improvement in depression symptoms following nitrous oxide treatment.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 20 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •English-speaking; age 20-60 years; BD-I or BD-II, current major depressive episode ≥4 weeks duration; MADRS≥22; taking ≥1 mood stabilizing medication/s (i.e. antimanic anticonvulsant, antipsychotic, and/or lithium).
排除标准
- •New medications or changes in dosing, or ECT or TMS, in the preceding 2 weeks; MADRS item 10, > 4; YMRS≥12; acute significant suicidality; psychosis; substance abuse (past 3 months); active major medical conditions (hepatic, renal, respiratory, or cardio/cerebrovascular disease; diabetes; esophageal reflux; sleep apnea); B12 deficiency/disorders; pregnant; MRI contraindications; history of adverse anaesthetic reactions; anaesthesia class >2; scuba diving in preceding week.
研究组 & 干预措施
Nitrous oxide
N2O-condition participants will inhale an initial mixture of 10% N2O in oxygen (O2) for 5 minutes, followed by 25% N2O in O2 for 20 minutes. N2O-condition participants will also receive 5ml intravenous saline concomitantly with 10% N2O, and again with 25% N2O.
干预措施: Nitrous Oxide (Drug)
Midazolam
Inhaled room air plus intravenous midazolam bolus (total 2mg). Midazolam-condition participants will receive intravenous infusions of 0.5mg midazolam in 5ml saline (start of 1st inhalation epoch), followed by 1.5mg midazolam in 5ml saline (start of 2nd inhalation epoch).
干预措施: Midazolam (Drug)
结局指标
主要结局
Change in Montgomery-Asberg Depression Scale (MADRS) score
时间窗: Assessed at baseline, an average of 3 days later, again at up to 5 days after baseline on the day of drug administration, and participants will be followed for 7 days after the drug administration
Measures mood symptom severity, used to select patients and assess treatment efficacy. Although other time-points will be examined, 24h was selected as the primary outcome to minimize the impact of acute sedation and psychoactive effects.
次要结局
- Young Mania Rating Scale (YMRS)(Assessed at baseline, an average of 3 days later, again at up to 5 days after baseline on the day of drug administration, and participants will be followed for 7 days after the drug administration)
- Blood Pressure(Measured an average of 3 days post-baseline and again approximately every hour on the drug administration day)
- Visual Analogue Scale(Assessed on the drug administration day and followed for 7 days post-drug administration)
- Height(Assessed an average of 3 days after baseline)
- Biomarkers (B12 and nitric oxide (NO))(Assessed an average of 3 days after baseline)
- The Clinician Administered Dissociative States Scale (CADSS)(Assessed on the drug administration day and followed for 7 days post-drug administration)
- General Information Sheet (Demographics)(Collected at baseline)
- Hamilton Anxiety Rating Scale (HAM-A)(Assessed on the drug administration day and followed for 7 days post-drug administration)
- Hamilton Depression Rating Scale (HDRS)(Assessed on the drug administration day and followed for 7 days post-drug administration)
- Patient Rated Inventory of Side Effects(Assessed on the drug administration day and followed for 7 days post-drug administration)
- CANTAB Medication Listing(Assessed an average of 3 days after baseline)
- Structured Clinical Interview for DSM Disorders(Assessed at baseline)
- Frontal Perfusion assessed using an MRI scan(Assessed approximately 5 days after baseline and post-drug administration)
- Heart Rate(Measured an average of 3 days post-baseline and again approximately every hour on the drug administration day)
- Brief Psychiatric Rating Scale(Assessed on the drug administration day and followed for 7 days post-drug administration)
- Weight(Assessed an average of 3 days after baseline)
- Beck Depression Inventory (BDI-II)(Assessed on the drug administration day and followed for 7 days post-drug administration)
- Endothelial Function assessed via RH-PAT using the EndoPAT.(Assessed an average of 3 days after baseline and lasts approximately 30 minutes)
研究者
Dr. Benjamin Goldstein
Associate Professor, University of Toronto
Sunnybrook Health Sciences Centre