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

Anesthesia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02624401
• Other study ID #: LOC-2016
• Status: Completed
• Phase: Phase 4
• First received: November 25, 2015
• Last updated: March 22, 2017
• Start date: January 2016
• Est. completion date: March 13, 2017

Study information

• Verified date: March 2017
• Source: University of Turku
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 160
• Est. completion date: March 13, 2017
• Est. primary completion date: March 13, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 30 Years

Eligibility

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

Related Conditions & MeSH terms

• Anesthesia
• Unconsciousness

Intervention

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

Locations

Country	Name	City	State
Finland	Turku PET Centre	Turku

Sponsors (5)

Lead Sponsor	Collaborator
University of Turku	Helsinki University, University of California, Irvine, University of Michigan, Yale University

Country where clinical trial is conducted

Finland, 

References & Publications (2)

Långsjö JW, Alkire MT, Kaskinoro K, Hayama H, Maksimow A, Kaisti KK, Aalto S, Aantaa R, Jääskeläinen SK, Revonsuo A, Scheinin H. Returning from oblivion: imaging the neural core of consciousness. J Neurosci. 2012 Apr 4;32(14):4935-43. doi: 10.1523/JNEUROSCI.4962-11.2012. — View Citation

Långsjo JW, Revonsuo A, Scheinin H. Harnessing anesthesia and brain imaging for the study of human consciousness. Curr Pharm Des. 2014;20(26):4211-24. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Drug concentration in plasma or end-tidal		1 hour
Primary	Regional cerebral metabolism of glucose	Comparison of responsive and unresponsive subjects	40 min
Secondary	EEG	64-channel EEG will be recorded and analyzed using time domain, spectral domain, functional connectivity, directed/effective connectivity and graph theoretical analysis methods.	1 hour
Secondary	Immunological effects	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.	2 hours
Secondary	Metabolomic effects	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.	2 hours
Secondary	Gene expression	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.	2 hours
Secondary	Psychological well-being	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.	2 hours
Secondary	Dream report	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.	1 hour

External Links

•   Academy of Finland: The MIND program
•   Research Group Home Page