A Randomized, Double-blind, Active Placebo-controlled, Multicenter Trial of Efficacy and Safety of Adjunctive Oral Ketamine vs Oral Midazolam for Major Depressive Episodes
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 220
- 试验地点
- 5
- 主要终点
- HAM-D
研究概览
简要总结
Patients with depression are acutely distressed, often suicidal, and unable to meet the demands of everyday life. If proven effective in a rigorously conducted multicenter randomized controlled trial (RCT), oral ketamine would provide an affordable and scalable, intervention suitable for integration into routine psychiatric services.This study will establish an indigenous, cost-effective therapeutic strategy that could improve accessibility, hasten therapeutic response, and inform treatment guidelines, if found to be safe and effective.
详细描述
Background: Conventional antidepressant treatment for major depressive episodes typically requires 3-6 weeks of drug use before meaningful clinical improvement is noted. Consequently, patients have to put their lives and responsibilities on hold while waiting for a therapeutic response.
Problem statement and rationale: There is a distinct need for a safe, acceptable, and effective, rapidly acting antidepressant in MDE to limit the impact on daily life. As an inexpensive, generic medication administered through a convenient route, oral ketamine has the potential to overcome the logistical barriers associated with existing ketamine formulations. If proven effective in a rigorous multicenter randomized controlled trial (RCT), oral ketamine would provide an affordable, scalable, and pragmatic intervention suitable for integration into routine psychiatric services.
Objectives- Primary: To assess the efficacy of adjunctive oral ketamine vs oral midazolam on clinical depression ratings at the end of study week 3- primary endpoint assessed using Hamilton Depression rating scale.
Secondary:
To assess the efficacy of adjunctive oral ketamine vs oral midazolam on clinical depression ratings at study day 2, day 7, and end of study weeks 2 and 4 and suicide ideation ratings at study day 2, study day 7, end of study week 2, week 3, and week 4.
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, Investigator, Outcomes Assessor)
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
- •Consenting adult outpatients or inpatients with at least moderately severe major depressive episode (MDE), denoted by HAM- D more than or equal to 20, associated with major depressive disorder or bipolar disorder, with diagnosis confirmed using a structured diagnostic interview.
排除标准
- •Patients with co-morbid obsessive-compulsive disorder or intellectual disability disorder or co-morbid substance dependence other than nicotine or patients concurrently receiving neuromodulation treatments or those with psychotic symptoms. Patients with current or ongoing suicide risk, such as active suicidal ideation with a specific plan or some intent in the last 3 days, will be excluded if they are treated as outpatients. Patients in whom, in the subjective opinion of the PI, the MDE symptoms appear to be significantly driven by acute life events or circumstances. Patients with abnormalities of concern detected in the electrocardiogram, or with uncontrolled hypertension or those with ongoing pregnancy or lactation
研究组 & 干预措施
Oral ketamine
In the first session, oral ketamine will be administered as a fixed 150 mg dose diluted in approximately 200 mL water and sipped across 20-30 minutes. In sessions 2-9 for oral ketamine, the dose will be lowered to 100-125mg in those who do not tolerate 150mg. If patients tolerate the first session well, we will increase the dose of ketamine to 175mg in the second session. If there is a negligible benefit and the intervention is tolerated, the dose of ketamine will be increased to 200 mg in the third session.
Further increase in ketamine will be done in the last week to 250mg, if deemed necessary, due to suboptimal response. Participants will remain nil per oral from one hour before until two hours after each session. Blood pressure and pulse rate will be monitored every 15 minutes for one hour or until normalization. Benzodiazepines such as clonazepam will be permitted for anxiety or agitation
干预措施: Oral ketamine (Drug)
Oral midazolam
The comparator arm will receive flexibly-dosed oral midazolam (5-7.5mg across all nine sessions, guided based on psychophysiological response to preserve the integrity of blinding), which will also be administered in approximately 200 mL of water, and sipped across 20-30 minutes
干预措施: Oral midazolam (Drug)
结局指标
主要结局
HAM-D
时间窗: End of study week 3 (±2 days)
Endpoint HAM-D scores
次要结局
- HAM-D(Study day 2 (± 1 day), day 7 (± 1 day), and the end of study weeks 2 (± 1 day) and week 4 (±2 days))
- MADRS(End of study day 2 (± 1 day), day 7 (± 1 day), end of study week 2 (±1 day), week 3 (± 2 days), and week 4 (± 2 days))
- PHQ - 9(End of study day 2 (± 1 day), day 7 (± 1 day), end of study week 2 (±1 day), week 3 (± 2 days), and week 4 (± 2 days))
- HAM-D/MADRS(End of study week 2 (±1 day), week 3 (± 2 days), and week 4 (± 2 days))
- Visual Analogue Scale for self-rated functioning & quality of life(End of study week 2 (±1 day), week 3 (± 2 days), and week 4 (± 2 days))
- Intrasession adverse effects checklist(During each treatment session until the end (at 2 hours))
- SAFTEE checklist(At study day 2 (± 1 day), day 7 (± 1 day), end of study week 2 (±1 day), week 3 (± 2 days), and week 4 (± 2 days))
研究者
Dr. Vikas Menon
Professor
Jawaharlal Institute of Postgraduate Medical Education & Research