The Neural Mechanisms of Anesthesia and Human Consciousness (Part 6)

University of Turku

Status and phase: Completed; Phase 4

Conditions: Unconsciousness; Anesthesia

Treatments: Drug: S-ketamine; Drug: Propofol; Drug: Sevoflurane; Drug: Placebo; Drug: Dexmedetomidine

Study type: Interventional

Funder types: Other

Identifiers

NCT02624401

LOC-2016

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 160 patients

Sex: Male

Ages: 18 to 30 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

1. Male
2. Age 18-30 years
3. Good general health i.e. American Society of Anesthesiologists (ASA) physical status I
4. Fluent in Finnish language
5. Right handedness
6. Written informed consent
7. Good sleep quality

Exclusion criteria

1. Chronic medication
2. History of alcohol and/or drug abuse
3. Strong susceptibility for allergic reactions
4. Serious nausea in connection with previous anesthesia
5. Strong susceptibility for nausea
6. Any use of drugs or alcohol during the 48 hours preceding anesthesia
7. Use of caffeine products 10-12 hours prior the study
8. Smoking
9. Clinically significant previous cardiac arrhythmia / cardiac conduction impairment
10. Clinically significant abnormality in prestudy laboratory tests
11. Positive result in the drug screening test
12. Blood donation within 90 days prior to the study
13. Participation in any medical study with an experimental drug or device during the preceding 60 days
14. The study subject has undergone a prior PET or SPECT study
15. Any contraindication to magnetic resonance imaging (MRI)
16. Hearing impairment
17. Detected unsuitability based on MRI scanning results if available before the PET scanning
18. Sleep disorder or severe sleep problem

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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160 participants in 5 patient groups, including a placebo group

Dexmedetomidine

Experimental group

Description:

Intravenous dexmedetomidine using target controlled infusion.

Treatment:

Drug: Dexmedetomidine

Propofol

Experimental group

Description:

Intravenous propofol using target controlled infusion.

Treatment:

Drug: Propofol

S-ketamine

Experimental group

Description:

Intravenous S-ketamine using target controlled infusion.

Treatment:

Drug: S-ketamine

Sevoflurane

Experimental group

Description:

Inhalational sevoflurane using target controlled inhalation.

Treatment:

Drug: Sevoflurane

Placebo

Placebo Comparator group

Description:

Intravenous saline.

Treatment:

Drug: Placebo