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

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ClinicalTrials.gov Identifier: NCT02624401
Recruitment Status : Completed
First Posted : December 8, 2015
Last Update Posted : March 27, 2017
Sponsor:
Collaborators:
University of California, Irvine
University of Michigan
Yale University
University of Helsinki
Information provided by (Responsible Party):
Harry Scheinin, University of Turku

Tracking Information
First Submitted Date  ICMJE November 25, 2015
First Posted Date  ICMJE December 8, 2015
Last Update Posted Date March 27, 2017
Study Start Date  ICMJE January 2016
Actual Primary Completion Date March 13, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 3, 2015)
Regional cerebral metabolism of glucose [ Time Frame: 40 min ]
Comparison of responsive and unresponsive subjects
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 3, 2015)
  • EEG [ Time Frame: 1 hour ]
    64-channel EEG will be recorded and analyzed using time domain, spectral domain, functional connectivity, directed/effective connectivity and graph theoretical analysis methods.
  • Immunological effects [ Time Frame: 2 hours ]
    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.
  • Metabolomic effects [ Time Frame: 2 hours ]
    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.
  • Gene expression [ Time Frame: 2 hours ]
    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 [ Time Frame: 2 hours ]
    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.
  • Dream report [ Time Frame: 1 hour ]
    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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: December 3, 2015)
Drug concentration in plasma or end-tidal [ Time Frame: 1 hour ]
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE The Neural Mechanisms of Anesthesia and Human Consciousness (Part 6)
Official Title  ICMJE The Neural Mechanisms of Anesthesia and Human Consciousness (Part 6)
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.
Detailed 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE
  • Anesthesia
  • Unconsciousness
Intervention  ICMJE
  • Drug: Dexmedetomidine
    Intravenous infusion
    Other Name: Dexdor
  • Drug: Propofol
    Intravenous infusion
    Other Name: Propofol-Lipuro
  • Drug: S-ketamine
    Intravenous infusion
    Other Name: Ketanest-S
  • Drug: Sevoflurane
    Inhalation
    Other Name: Sevorane
  • Drug: Placebo
    Intravenous infusion of saline (Ringer's Acetate)
Study Arms  ICMJE
  • Experimental: Dexmedetomidine
    Intravenous dexmedetomidine using target controlled infusion.
    Intervention: Drug: Dexmedetomidine
  • Experimental: Propofol
    Intravenous propofol using target controlled infusion.
    Intervention: Drug: Propofol
  • Experimental: S-ketamine
    Intravenous S-ketamine using target controlled infusion.
    Intervention: Drug: S-ketamine
  • Experimental: Sevoflurane
    Inhalational sevoflurane using target controlled inhalation.
    Intervention: Drug: Sevoflurane
  • Placebo Comparator: Placebo
    Intravenous saline.
    Intervention: Drug: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 3, 2015)
160
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE March 13, 2017
Actual Primary Completion Date March 13, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years to 30 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Finland
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02624401
Other Study ID Numbers  ICMJE LOC-2016
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Harry Scheinin, University of Turku
Study Sponsor  ICMJE University of Turku
Collaborators  ICMJE
  • University of California, Irvine
  • University of Michigan
  • Yale University
  • University of Helsinki
Investigators  ICMJE
Principal Investigator: Harry Scheinin, MD Turku PET Centre, University of Turku, Turku, Finland
PRS Account University of Turku
Verification Date March 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP