NCT01889004

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
47

participants targeted

Target at P25-P50 for phase_4

Timeline
Completed

Started Feb 2014

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

June 23, 2013

Completed
5 days until next milestone

First Posted

Study publicly available on registry

June 28, 2013

Completed
7 months until next milestone

Study Start

First participant enrolled

February 1, 2014

Completed
1.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2016

Completed
Last Updated

January 11, 2016

Status Verified

January 1, 2016

Enrollment Period

1.9 years

First QC Date

June 23, 2013

Last Update Submit

January 8, 2016

Conditions

Consciousness, Level Altered

Keywords

Cerebral blood flowConsciousnessDexmedetomidineEEGEvent related potentialsFunctional magnetic resonance imagingGeneral anesthesiaPositron emission tomographyPropofol

Outcome Measures

Primary Outcomes (1)

  • 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

Secondary Outcomes (3)

  • EEG

    Continuous data collection during five separate days within 2 months

  • Functional magnetic resonance imaging (fMRI)

    Several measurements during one day

  • Event related potentials

    Several time points during five separate days within 2 months

Other Outcomes (1)

  • Drug concentration in plasma

    Several times points during two or three separate days within 2 months

Study Arms (2)

Dexmedetomidine

EXPERIMENTAL

Intravenous dexmedetomidine using target controlled infusion

Drug: Dexmedetomidine

Propofol

EXPERIMENTAL

Intravenous propofol using target controlled infusion

Drug: Propofol

Interventions

DexmedetomidineDRUG

Escalating concentrations until loss of responsiveness

Also known as: Dexdor
Dexmedetomidine
PropofolDRUG

Escalating concentrations until loss of responsiveness

Also known as: Propofol-Lipuro
Propofol

Eligibility Criteria

Age20 Years - 30 Years
Sexmale
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • 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

You may not qualify if:

  • 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)
  • +4 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Turku PET Centre

Turku, FI-20521, Finland

Location

Related Publications (6)

  • 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.

    PMID: 22492049BACKGROUND

  • Valli K, Radek L, Kallionpaa RE, Scheinin A, Langsjo J, Kaisti K, Kantonen O, Korhonen J, Vahlberg T, Revonsuo A, Scheinin H. Subjective experiences during dexmedetomidine- or propofol-induced unresponsiveness and non-rapid eye movement sleep in healthy male subjects. Br J Anaesth. 2023 Aug;131(2):348-359. doi: 10.1016/j.bja.2023.04.026. Epub 2023 May 31.

    PMID: 37268445DERIVED

  • 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.

    PMID: 32773216DERIVED

  • 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.

    PMID: 31805854DERIVED

  • 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.

    PMID: 29935582DERIVED

  • 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.

    PMID: 29935581DERIVED

Related Links

MeSH Terms

Conditions

Consciousness Disorders

Interventions

DexmedetomidinePropofol

Condition Hierarchy (Ancestors)

Neurobehavioral ManifestationsNeurologic ManifestationsNervous System DiseasesSigns and SymptomsPathological Conditions, Signs and SymptomsNeurocognitive DisordersMental Disorders

Intervention Hierarchy (Ancestors)

ImidazolesAzolesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsPhenolsBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsOrganic Chemicals

Study Officials

  • Harry Scheinin, MD

    University of Turku

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
NONE
Purpose
BASIC SCIENCE
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Adjunct Professor

Study Record Dates

First Submitted

June 23, 2013

First Posted

June 28, 2013

Study Start

February 1, 2014

Primary Completion

January 1, 2016

Study Completion

January 1, 2016

Last Updated

January 11, 2016

Record last verified: 2016-01

Locations

FI(1)