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

Ketamine

Brief Summary

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.

Intervention / Treatment

  • Dexmedetomidine (DRUG)
    Intravenous infusion
  • Propofol (DRUG)
    Intravenous infusion
  • S-ketamine (DRUG)
    Intravenous infusion
  • Sevoflurane (DRUG)
    Inhalation
  • Placebo (DRUG)
    Intravenous infusion of saline (Ringer's Acetate)

Condition or Disease

  • Anesthesia
  • Unconsciousness

Phase

  • Phase 4

    • Study Design

    Study type: INTERVENTIONAL
    Status: Completed
    Study results: No Results Available
    Age: 18 Years to 30 Years
    Enrollment: 160 (ACTUAL)
    Funded by: Other
    Allocation: Randomized
    Primary Purpose: Basic Science

    Masking

    Clinical Trial Dates

    Start date: Jan 01, 2016
    Primary Completion: Mar 13, 2017 ACTUAL
    Completion Date: Mar 13, 2017 ACTUAL
    Study First Posted: Dec 08, 2015 ESTIMATED
    Results First Posted: Aug 31, 2020
    Last Updated: Mar 22, 2017

    Sponsors / Collaborators

    Lead Sponsor: University of Turku
    Responsible Party: N/A

    Location

    Turku, Southwest Finland, Finland

    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.

    Participant Groups

    • Intravenous dexmedetomidine using target controlled infusion.

    • Intravenous propofol using target controlled infusion.

    • Intravenous S-ketamine using target controlled infusion.

    • Inhalational sevoflurane using target controlled inhalation.

    • Intravenous saline.

    Eligibility Criteria

    Sex: Male
    Minimum Age: 18
    Maximum Age: 30
    Age Groups: Adult
    Healthy Volunteers: Yes

    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

    Primary Outcomes

    • Comparison of responsive and unresponsive subjects

    Secondary Outcomes

    • 64-channel EEG will be recorded and analyzed using time domain, spectral domain, functional connectivity, directed/effective connectivity and graph theoretical analysis methods.

    • Blood samples will be draw at baseline (without drug), at the end of study drug administration and after PET scanning for the measurement of approximately 50 cytokines, chemokines and growth factors.

    • Blood samples will be drawn at baseline (without drug), at the end of drug administration and after PET scanning for the measurement of more than 200 serum measures, including lipoprotein subclass distribution and lipoprotein particle concentration, low molecular weight metabolites, such as amino acids, 3-hydroxybutyrate and creatinine, and detailed molecular information on serum lipids, including free and esterified cholesterol, sphingomyelin and fatty acid saturation.

    • Blood samples will be collected at baseline (without drug), at the end of drug administration and after PET scanning for the measurement of RNA expression using whole genome microarray-based, massively parallel sequencing or quantitative reverse-transcription polymerase chain reaction based methods.

    • Psychological well-being and ill-being will be measured with a battery of scientifically validated scales just before initiating the study session and at the end of the study session.

    • After terminating PET imaging, a structured interview is immediately conducted to verify a recollection or absence of recollection of subjective experiences during possible loss of responsiveness.

    Other Outcomes
    • Drug concentration in plasma or end-tidal 1 hour

    More Details

    NCT Number: NCT02624401
    Other IDs: LOC-2016
    Study URL: https://clinicaltrials.gov/study/NCT02624401
    Last updated: Sep 29, 2023