The Neural Mechanisms of Anesthesia and Human Consciousness

Consciousness, Level Altered Clinical Trial

— LOC-2013  

Official title:

The Neural Mechanisms of Anesthesia and Human Consciousness (LOC-2013)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01889004
• Other study ID #: LOC-2013
• Secondary ID: 2664672013-00149
• Status: Completed
• Phase: Phase 4
• First received: June 23, 2013
• Last updated: January 8, 2016
• Start date: February 2014
• Est. completion date: January 2016

Study information

• Verified date: January 2016
• Source: University of Turku
• Contact: n/a
• Is FDA regulated: No
• Health authority: Finland: Finnish Medicines AgencyFinland: Ethics CommitteeEuropean Union: European Medicines Agency
• Study type: Interventional

Clinical Trial 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.

Description:

(not needed)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 47
• Est. completion date: January 2016
• Est. primary completion date: January 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 20 Years to 30 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Consciousness, Level Altered

Intervention

Drug:
• Dexmedetomidine
Escalating concentrations until loss of responsiveness
• Propofol
Escalating concentrations until loss of responsiveness

Locations

Country	Name	City	State
Finland	Turku PET Centre	Turku

Sponsors (3)

Lead Sponsor	Collaborator
University of Turku	Academy of Finland, Hospital District of Southwestern Finland

Country where clinical trial is conducted

Finland, 

References & Publications (1)

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Drug concentration in plasma		Several times points during two or three separate days within 2 months	No
Primary	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.	Several measurements during two separate days within 2 months	No
Secondary	EEG		Continuous data collection during five separate days within 2 months	No
Secondary	Functional magnetic resonance imaging (fMRI)		Several measurements during one day	No
Secondary	Event related potentials		Several time points during five separate days within 2 months	No

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