The Neural Mechanisms of Anesthesia and Human Consciousness (Part 6)
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 160
- 试验地点
- 1
- 主要终点
- Regional cerebral metabolism of glucose
研究概览
简要总结
Positron Emission Tomography (PET), Magnetic Resonance Imaging (MRI) and electroencephalography (EEG) studies will be carried out to reveal the neural correlates of consciousness. Consciousness of the subjects will be manipulated with anesthetic agents dexmedetomidine, propofol, S-ketamine and sevoflurane. One-hundred-and-sixty (160) healthy male subjects will be recruited to receive EC50 concentration of the anesthetic (40 dexmedetomidine, 40 propofol, 20 S-ketamine, 40 sevoflurane) or placebo (20) while being imaged for cerebral metabolic rate of glucose (CMRglu). Also genetic, immunological and metabolomics samples will be taken and analysed to find possible genetic factors explaining the variability in drug response and to find chemical fingerprints of acute drug effect.
详细描述
The explanation of consciousness poses one of the greatest challenges to science and philosophy in the 21st century. It remains unclear what consciousness is and how it emerges from brain activity. Positron Emission Tomography (PET), Magnetic Resonance Imaging (MRI) and electroencephalography (EEG) studies will be carried out to reveal the neural correlates of consciousness. Consciousness of the subjects will be manipulated with anesthetic agents dexmedetomidine acting through α2-agonism, with propofol and sevoflurane both mainly acting through the enhancement of gamma-aminobutyric acid (GABA) system, and with S-ketamine acting through N-methyl-D-aspartate (NMDA) receptor antagonism. One-hundred-and-sixty (160) healthy male subjects will be recruited to receive EC50 concentration of either dexmedetomidine, propofol, S-ketamine or sevoflurane, or placebo while being imaged for cerebral metabolic rate of glucose (CMRglu). 40 subjects will receive dexmedetomidine, 40 subjects propofol, 20 subjects S-ketamine, 40 subjects sevoflurane and 20 subjects will receive placebo. Also genetic, immunological and metabolomics samples will be taken and analysed to find possible genetic factors explaining the variability in drug response and to find possible immunological and chemical fingerprints of acute drug effect.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 30 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Age 18-30 years
- •Good general health i.e. American Society of Anesthesiologists (ASA) physical status I
- •Fluent in Finnish language
- •Right handedness
- •Written informed consent
- •Good sleep quality
排除标准
- •Chronic medication
- •History of alcohol and/or drug abuse
- •Strong susceptibility for allergic reactions
- •Serious nausea in connection with previous anesthesia
- •Strong susceptibility for nausea
- •Any use of drugs or alcohol during the 48 hours preceding anesthesia
- •Use of caffeine products 10-12 hours prior the study
- •Clinically significant previous cardiac arrhythmia / cardiac conduction impairment
- •Clinically significant abnormality in prestudy laboratory tests
- •Positive result in the drug screening test
- •Blood donation within 90 days prior to the study
- •Participation in any medical study with an experimental drug or device during the preceding 60 days
- •The study subject has undergone a prior PET or SPECT study
- •Any contraindication to magnetic resonance imaging (MRI)
- •Hearing impairment
- •Detected unsuitability based on MRI scanning results if available before the PET scanning
- •Sleep disorder or severe sleep problem
研究组 & 干预措施
Placebo
Intravenous saline.
干预措施: Placebo (Drug)
Dexmedetomidine
Intravenous dexmedetomidine using target controlled infusion.
干预措施: Dexmedetomidine (Drug)
Propofol
Intravenous propofol using target controlled infusion.
干预措施: Propofol (Drug)
S-ketamine
Intravenous S-ketamine using target controlled infusion.
干预措施: S-ketamine (Drug)
Sevoflurane
Inhalational sevoflurane using target controlled inhalation.
干预措施: Sevoflurane (Drug)
结局指标
主要结局
Regional cerebral metabolism of glucose
时间窗: 40 min
Comparison of responsive and unresponsive subjects
次要结局
- Immunological effects(2 hours)
- Gene expression(2 hours)
- Psychological well-being(2 hours)
- Dream report(1 hour)
- EEG(1 hour)
- Metabolomic effects(2 hours)
研究者
Harry Scheinin
Adjunct Professor
University of Turku