The Neural Mechanisms of Anesthesia and Human Consciousness (LOC-2013)
Primary Purpose
Consciousness, Level Altered
Status
Completed
Phase
Phase 4
Locations
Finland
Study Type
Interventional
Intervention
Dexmedetomidine
Propofol
Sponsored by
About this trial
This is an interventional basic science trial for Consciousness, Level Altered focused on measuring Cerebral blood flow, Consciousness, Dexmedetomidine, EEG, Event related potentials, Functional magnetic resonance imaging, General anesthesia, Positron emission tomography, Propofol
Eligibility Criteria
Inclusion Criteria:
- Male
- Age 20-30 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
Exclusion Criteria:
- 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, 24 hours before sleep studies
- Smoking
- 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 initial electrophysiological measurements
- Detected unsuitability based on MRI scanning results
- Sleep disorder or severe sleep problem
Sites / Locations
- Turku PET Centre
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Dexmedetomidine
Propofol
Arm Description
Intravenous dexmedetomidine using target controlled infusion
Intravenous propofol using target controlled infusion
Outcomes
Primary Outcome Measures
Regional cerebral blood flow
Altogether 14 PET scans during two separate study days. Cerebral blood flow changes will be used as surrogates for changes in regional brain activity.
Secondary Outcome Measures
EEG
Functional magnetic resonance imaging (fMRI)
Event related potentials
Full Information
NCT ID
NCT01889004
First Posted
June 23, 2013
Last Updated
January 8, 2016
Sponsor
University of Turku
Collaborators
Academy of Finland, Hospital District of Southwestern Finland
1. Study Identification
Unique Protocol Identification Number
NCT01889004
Brief Title
The Neural Mechanisms of Anesthesia and Human Consciousness
Acronym
LOC-2013
Official Title
The Neural Mechanisms of Anesthesia and Human Consciousness (LOC-2013)
Study Type
Interventional
2. Study Status
Record Verification Date
January 2016
Overall Recruitment Status
Completed
Study Start Date
February 2014 (undefined)
Primary Completion Date
January 2016 (Actual)
Study Completion Date
January 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Turku
Collaborators
Academy of Finland, Hospital District of Southwestern Finland
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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. By studying anesthesia and sleep, the investigators aim to reveal what happens in the brain when consciousness is lost and when it returns. During the study, a series of Positron Emission Tomography (PET), Magnetic Resonance Imaging (MRI) and electroencephalography (EEG) studies will be carried out on healthy male subjects to reveal the neural correlates of consciousness. Consciousness of the subjects will be manipulated with normal sleep and anesthetic agents dexmedetomidine and propofol.
First, various neurophysiological tools to separate consciousness, connectedness and responsiveness during normal sleep will be tested. The most suitable methods and subjects will be selected and then tested during anesthetic-induced sedation and loss of responsiveness (LOR). The anesthetics (dexmedetomidine or propofol) will be administered as target-controlled infusions (TCI) with step-wise concentration-increments until LOR is detected. Then, TCIs are repeated in the same subjects but adjusted according to the individual drug target concentrations sufficient for LOR, and a series of PET perfusion imaging measurements will be performed to obtain the brain activity information in various states of consciousness. The same subjects will then be imaged with PET for brain activity after sleep deprivation (awake), during various sleep stages and immediately after awakening. Finally, ten dexmedetomidine subjects will be given the drug once more, and functional MRI (fMRI) data will be collected at various states of consciousness before and during verbal and nonverbal vocalizations. EEG will be continuously collected in all sessions. The depth of anesthesia will be measured using quantitative EEG and bispectral index (BIS) monitoring.
The results may lead to the discovery of new and better objective indicators of the depth of anesthesia and consciousness, and new insights into the understanding of neural mechanisms behind drug-induced loss of consciousness and ultimately the mechanisms of action of (general) anesthetics as well as consciousness itself.
Detailed Description
(not needed)
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Consciousness, Level Altered
Keywords
Cerebral blood flow, Consciousness, Dexmedetomidine, EEG, Event related potentials, Functional magnetic resonance imaging, General anesthesia, Positron emission tomography, Propofol
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
47 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Dexmedetomidine
Arm Type
Experimental
Arm Description
Intravenous dexmedetomidine using target controlled infusion
Arm Title
Propofol
Arm Type
Experimental
Arm Description
Intravenous propofol using target controlled infusion
Intervention Type
Drug
Intervention Name(s)
Dexmedetomidine
Other Intervention Name(s)
Dexdor
Intervention Description
Escalating concentrations until loss of responsiveness
Intervention Type
Drug
Intervention Name(s)
Propofol
Other Intervention Name(s)
Propofol-Lipuro
Intervention Description
Escalating concentrations until loss of responsiveness
Primary Outcome Measure Information:
Title
Regional cerebral blood flow
Description
Altogether 14 PET scans during two separate study days. Cerebral blood flow changes will be used as surrogates for changes in regional brain activity.
Time Frame
Several measurements during two separate days within 2 months
Secondary Outcome Measure Information:
Title
EEG
Time Frame
Continuous data collection during five separate days within 2 months
Title
Functional magnetic resonance imaging (fMRI)
Time Frame
Several measurements during one day
Title
Event related potentials
Time Frame
Several time points during five separate days within 2 months
Other Pre-specified Outcome Measures:
Title
Drug concentration in plasma
Time Frame
Several times points during two or three separate days within 2 months
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
30 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Male
Age 20-30 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
Exclusion Criteria:
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, 24 hours before sleep studies
Smoking
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 initial electrophysiological measurements
Detected unsuitability based on MRI scanning results
Sleep disorder or severe sleep problem
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Harry Scheinin, MD
Organizational Affiliation
University of Turku
Official's Role
Principal Investigator
Facility Information:
Facility Name
Turku PET Centre
City
Turku
ZIP/Postal Code
FI-20521
Country
Finland
12. IPD Sharing Statement
Citations:
PubMed Identifier
22492049
Citation
Langsjo JW, Alkire MT, Kaskinoro K, Hayama H, Maksimow A, Kaisti KK, Aalto S, Aantaa R, Jaaskelainen 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.
Results Reference
background
PubMed Identifier
32773216
Citation
Kallionpaa RE, Valli K, Scheinin A, Langsjo J, Maksimow A, Vahlberg T, Revonsuo A, Scheinin H, Mashour GA, Li D. Alpha band frontal connectivity is a state-specific electroencephalographic correlate of unresponsiveness during exposure to dexmedetomidine and propofol. Br J Anaesth. 2020 Oct;125(4):518-528. doi: 10.1016/j.bja.2020.05.068. Epub 2020 Aug 7.
Results Reference
derived
PubMed Identifier
31805854
Citation
Kallioinen M, Scheinin A, Maksimow M, Langsjo J, Kaisti K, Takala R, Vahlberg T, Valli K, Salmi M, Scheinin H, Maksimow A. The influence of dexmedetomidine and propofol on circulating cytokine levels in healthy subjects. BMC Anesthesiol. 2019 Dec 5;19(1):222. doi: 10.1186/s12871-019-0895-3.
Results Reference
derived
PubMed Identifier
29935582
Citation
Kallionpaa RE, Scheinin A, Kallionpaa RA, Sandman N, Kallioinen M, Laitio R, Laitio T, Kaskinoro K, Kuusela T, Revonsuo A, Scheinin H, Valli K. Spoken words are processed during dexmedetomidine-induced unresponsiveness. Br J Anaesth. 2018 Jul;121(1):270-280. doi: 10.1016/j.bja.2018.04.032. Epub 2018 May 23.
Results Reference
derived
PubMed Identifier
29935581
Citation
Radek L, Kallionpaa RE, Karvonen M, Scheinin A, Maksimow A, Langsjo J, Kaisti K, Vahlberg T, Revonsuo A, Scheinin H, Valli K. Dreaming and awareness during dexmedetomidine- and propofol-induced unresponsiveness. Br J Anaesth. 2018 Jul;121(1):260-269. doi: 10.1016/j.bja.2018.03.014. Epub 2018 May 10.
Results Reference
derived
Links:
URL
http://www.turkupetcentre.fi/index.php?option=com_content&view=article&id=268&Itemid=27
Description
Research Group Home Page
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