- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01889004
The Neural Mechanisms of Anesthesia and Human Consciousness (LOC-2013)
The Neural Mechanisms of Anesthesia and Human Consciousness (LOC-2013)
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.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
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Turku, Finland, FI-20521
- Turku PET Centre
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Dexmedetomidine
Intravenous dexmedetomidine using target controlled infusion
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Escalating concentrations until loss of responsiveness
Other Names:
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Experimental: Propofol
Intravenous propofol using target controlled infusion
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Escalating concentrations until loss of responsiveness
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Regional cerebral blood flow
Time Frame: Several measurements during two separate days within 2 months
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Altogether 14 PET scans during two separate study days.
Cerebral blood flow changes will be used as surrogates for changes in regional brain activity.
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Several measurements during two separate days within 2 months
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
EEG
Time Frame: Continuous data collection during five separate days within 2 months
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Continuous data collection during five separate days within 2 months
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Functional magnetic resonance imaging (fMRI)
Time Frame: Several measurements during one day
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Several measurements during one day
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Event related potentials
Time Frame: Several time points during five separate days within 2 months
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Several time points during five separate days within 2 months
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Other Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Drug concentration in plasma
Time Frame: Several times points during two or three separate days within 2 months
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Several times points during two or three separate days within 2 months
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Harry Scheinin, MD, University of Turku
Publications and helpful links
General Publications
- 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.
- 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.
- 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.
- 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.
- 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.
Helpful Links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Mental Disorders
- Nervous System Diseases
- Neurologic Manifestations
- Neurobehavioral Manifestations
- Neurocognitive Disorders
- Consciousness Disorders
- Physiological Effects of Drugs
- Adrenergic Agents
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Central Nervous System Depressants
- Peripheral Nervous System Agents
- Analgesics
- Sensory System Agents
- Anesthetics, Intravenous
- Anesthetics, General
- Anesthetics
- Analgesics, Non-Narcotic
- Adrenergic alpha-2 Receptor Agonists
- Adrenergic alpha-Agonists
- Adrenergic Agonists
- Hypnotics and Sedatives
- Propofol
- Dexmedetomidine
Other Study ID Numbers
- LOC-2013
- 266467 (Other Grant/Funding Number: Academy of Finland)
- 2013-001496-21 (EudraCT Number)
- KLnro 72/2013 (Registry Identifier: Finnish Medicines Agency (Fimea))
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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