NCT02624401

Brief 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.

Trial Health

87
On Track

Trial Health Score

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

Enrollment
160

participants targeted

Target at P50-P75 for phase_4

Timeline
Completed

Started Jan 2016

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

November 25, 2015

Completed
13 days until next milestone

First Posted

Study publicly available on registry

December 8, 2015

Completed
24 days until next milestone

Study Start

First participant enrolled

January 1, 2016

Completed
1.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 13, 2017

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 13, 2017

Completed
Last Updated

March 27, 2017

Status Verified

March 1, 2017

Enrollment Period

1.2 years

First QC Date

November 25, 2015

Last Update Submit

March 22, 2017

Conditions

AnesthesiaUnconsciousness

Outcome Measures

Primary Outcomes (1)

  • Regional cerebral metabolism of glucose

    Comparison of responsive and unresponsive subjects

    40 min

Secondary Outcomes (6)

  • EEG

    1 hour

  • Immunological effects

    2 hours

  • Metabolomic effects

    2 hours

  • Gene expression

    2 hours

  • Psychological well-being

    2 hours

  • +1 more secondary outcomes

Other Outcomes (1)

  • Drug concentration in plasma or end-tidal

    1 hour

Study Arms (5)

Dexmedetomidine

EXPERIMENTAL

Intravenous dexmedetomidine using target controlled infusion.

Drug: Dexmedetomidine

Propofol

EXPERIMENTAL

Intravenous propofol using target controlled infusion.

Drug: Propofol

S-ketamine

EXPERIMENTAL

Intravenous S-ketamine using target controlled infusion.

Drug: S-ketamine

Sevoflurane

EXPERIMENTAL

Inhalational sevoflurane using target controlled inhalation.

Drug: Sevoflurane

Placebo

PLACEBO COMPARATOR

Intravenous saline.

Drug: Placebo

Interventions

DexmedetomidineDRUG

Intravenous infusion

Also known as: Dexdor
Dexmedetomidine
PropofolDRUG

Intravenous infusion

Also known as: Propofol-Lipuro
Propofol
S-ketamineDRUG

Intravenous infusion

Also known as: Ketanest-S
S-ketamine
SevofluraneDRUG

Inhalation

Also known as: Sevorane
Sevoflurane
PlaceboDRUG

Intravenous infusion of saline (Ringer's Acetate)

Placebo

Eligibility Criteria

Age18 Years - 30 Years
Sexmale
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • Male
  • Age 18-30 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
  • 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)
  • +3 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Turku PET Centre

Turku, FI-20521, Finland

Location

Related Publications (5)

  • 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

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

    PMID: 24025060BACKGROUND

  • Nummela A, Laaksonen L, Scheinin A, Kaisti K, Vahlberg T, Neuvonen M, Valli K, Revonsuo A, Perola M, Niemi M, Scheinin H, Laitio T. Circulating oxylipin and bile acid profiles of dexmedetomidine, propofol, sevoflurane, and S-ketamine: a randomised controlled trial using tandem mass spectrometry. BJA Open. 2022 Dec 12;4:100114. doi: 10.1016/j.bjao.2022.100114. eCollection 2022 Dec.

    PMID: 37588789DERIVED

  • Nummela AJ, Laaksonen LT, Laitio TT, Kallionpaa RE, Langsjo JW, Scheinin JM, Vahlberg TJ, Koskela HT, Aittomaki V, Valli KJ, Revonsuo A, Niemi M, Perola M, Scheinin H. Effects of dexmedetomidine, propofol, sevoflurane and S-ketamine on the human metabolome: A randomised trial using nuclear magnetic resonance spectroscopy. Eur J Anaesthesiol. 2022 Jun 1;39(6):521-532. doi: 10.1097/EJA.0000000000001591. Epub 2021 Sep 22.

    PMID: 34534172DERIVED

  • Laaksonen L, Kallioinen M, Langsjo J, Laitio T, Scheinin A, Scheinin J, Kaisti K, Maksimow A, Kallionpaa RE, Rajala V, Johansson J, Kantonen O, Nyman M, Siren S, Valli K, Revonsuo A, Solin O, Vahlberg T, Alkire M, Scheinin H. Comparative effects of dexmedetomidine, propofol, sevoflurane, and S-ketamine on regional cerebral glucose metabolism in humans: a positron emission tomography study. Br J Anaesth. 2018 Jul;121(1):281-290. doi: 10.1016/j.bja.2018.04.008. Epub 2018 May 8.

    PMID: 29935583DERIVED

MeSH Terms

Conditions

Unconsciousness

Interventions

DexmedetomidinePropofolEsketamineSevoflurane

Condition Hierarchy (Ancestors)

Consciousness DisordersNeurobehavioral ManifestationsNeurologic ManifestationsNervous System DiseasesSigns and SymptomsPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

ImidazolesAzolesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsPhenolsBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsMethyl EthersEthersHydrocarbons, FluorinatedHydrocarbons, Halogenated

Study Officials

  • Harry Scheinin, MD

    Turku PET Centre, University of Turku, Turku, Finland

    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

November 25, 2015

First Posted

December 8, 2015

Study Start

January 1, 2016

Primary Completion

March 13, 2017

Study Completion

March 13, 2017

Last Updated

March 27, 2017

Record last verified: 2017-03

Data Sharing

IPD Sharing
Will not share

Locations

FI(1)