Investigating Glutamate and Opioid Mechanisms of Antidepressant Response to Ketamine
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 入组人数
- 27
- 试验地点
- 1
- 主要终点
- Change in Glutamate
研究概览
简要总结
The overarching aim of this research is to determine the acute effects of ketamine on brain glutamate, functional connectivity and cerebral blood flow in treatment-resistant depression, explore whether the effects are attenuated by the opioid receptor antagonist naltrexone and relate these findings to antidepressant response.
详细描述
The study is a randomised, double-blind, crossover design with two treatment conditions: oral placebo or oral naltrexone preceding ketamine infusion during neuroimaging in subjects with treatment-resistant depression.
Each subject will participate in two imaging sessions on two separate days. Each subject will receive a dose of ketamine (IV infusion, 0.5 mg/kg over 40 minutes) during each scan. Subjects will receive either oral placebo or naltrexone 50 mg, 45 minutes before the initiation of each of the ketamine infusions.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
A: Visit 1) Naltrexone + Ketamine, Visit 2) Placebo + Ketamine
Participants randomly assigned to arm A:
VISIT 1) Naltrexone 50mg before the administration of ketamine 0.5mg/kg.
VISIT 2) Placebo before the administration of ketamine 0.5mg/kg.
Study visits are separated by 14-28 days.
干预措施: Naltrexone (Drug)
A: Visit 1) Naltrexone + Ketamine, Visit 2) Placebo + Ketamine
Participants randomly assigned to arm A:
VISIT 1) Naltrexone 50mg before the administration of ketamine 0.5mg/kg.
VISIT 2) Placebo before the administration of ketamine 0.5mg/kg.
Study visits are separated by 14-28 days.
干预措施: Placebo (Drug)
A: Visit 1) Naltrexone + Ketamine, Visit 2) Placebo + Ketamine
Participants randomly assigned to arm A:
VISIT 1) Naltrexone 50mg before the administration of ketamine 0.5mg/kg.
VISIT 2) Placebo before the administration of ketamine 0.5mg/kg.
Study visits are separated by 14-28 days.
干预措施: Ketamine (Drug)
B: Visit 1) Placebo + Ketamine, Visit 2) Naltrexone + Ketamine
Participants randomly assigned to arm B:
VISIT 1) Placebo before the administration of ketamine 0.5mg/kg.
VISIT 2) Naltrexone 50mg before the administration of ketamine 0.5mg/kg.
Study visits are separated by 14-28 days.
干预措施: Naltrexone (Drug)
B: Visit 1) Placebo + Ketamine, Visit 2) Naltrexone + Ketamine
Participants randomly assigned to arm B:
VISIT 1) Placebo before the administration of ketamine 0.5mg/kg.
VISIT 2) Naltrexone 50mg before the administration of ketamine 0.5mg/kg.
Study visits are separated by 14-28 days.
干预措施: Placebo (Drug)
B: Visit 1) Placebo + Ketamine, Visit 2) Naltrexone + Ketamine
Participants randomly assigned to arm B:
VISIT 1) Placebo before the administration of ketamine 0.5mg/kg.
VISIT 2) Naltrexone 50mg before the administration of ketamine 0.5mg/kg.
Study visits are separated by 14-28 days.
干预措施: Ketamine (Drug)
结局指标
主要结局
Change in Glutamate
时间窗: Changes will be in the same session comparing the ketamine infusion period to the pre-ketamine infusion baseline
Compare changes in glutamate and GLX (glutamate +glutamine), referenced to total creatine (tCr), during ketamine infusion as measured by functional magnetic resonance spectroscopy (1H-fMRS) for naltrexone versus placebo pre-treatment conditions. Hypothesis: There will be a significant increase in glutamate measures during ketamine administration compared to a resting baseline condition in a medial prefrontal cortex (mPFC) /anterior cingulate cortex (ACC) region. Pre-treatment with naltrexone will attenuate this increase.
次要结局
- Change in Resting State Functional Connectivity(Changes will be in the same session comparing post-infusion (immediately after ketamine infusion) to the pre-ketamine infusion baseline)
- Change in Cerebral Blood Flow(Changes will be in the same session comparing data collected 30 minutes after the ketamine infusion commences to the pre-ketamine infusion baseline)