Consciousness, Level AlteredPhase 4LOC-2013NCT01889004
The Neural Mechanisms of Anesthesia and Human Consciousness
A Phase 4 study testing Dexmedetomidine and Propofol in people with Consciousness, Level Altered, run by University of Turku at 1 site in Finland.
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. Read more about this study
- Who is it for?
- Ages 20 to 30 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Consciousness, Level Altered
- What is being tested?
- Dexmedetomidine and Propofol
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 47 participants
- Where
- 1 siteFinland
- Study dates
- Feb 2014to Jan 2016
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 30 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 19Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the detailed description
(not needed)
- Conditions
- Consciousness, Level Altered
- Being tested
- Dexmedetomidine, Propofol
- Keywords
- Cerebral blood flow, Consciousness, Dexmedetomidine, EEG, Event related potentials, Functional magnetic resonance imaging, General anesthesia, Positron emission tomography, Propofol
- Medical subject headings
- Consciousness Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DexmedetomidineDrug
Also called Dexdor
Escalating concentrations until loss of responsiveness
PropofolDrug
Also called Propofol-Lipuro
Escalating concentrations until loss of responsiveness
| Study group | Role | What they receive |
|---|---|---|
| Dexmedetomidine | Experimental | Intravenous dexmedetomidine using target controlled infusion Receives: Drug: Dexmedetomidine |
| Propofol | Experimental | Intravenous propofol using target controlled infusion Receives: Drug: Propofol |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Several measurements during two separate days within 2 months
Secondary outcomes (3)
EEG
Measured: Continuous data collection during five separate days within 2 months
Functional magnetic resonance imaging (fMRI)
Measured: Several measurements during one day
Event related potentials
Measured: Several time points during five separate days within 2 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jun 2013 (estimated)
- Study startFeb 2014
- Primary completionJan 2016
- Study completionJan 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Consciousness, Level AlteredStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 47 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Turku
- Sponsor type
- University, hospital or other
- Collaborators
- Academy of Finland, Hospital District of Southwestern Finland
- Responsible party
- Principal investigator, Harry Scheinin, University of Turku
- Investigators
- Harry Scheinin, MD, Principal investigator, University of Turku
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01889004
- Sponsor's protocol ID
- LOC-2013
- Other IDs
- 266467, 2013-001496-21, KLnro 72/2013
- Acronym
- LOC-2013
- Status last verified
- Jan 2016
- First submitted
- 23 Jun 2013
- Last updated
- 11 Jan 2016
- Results posted
- No
- Data monitoring committee
- No
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.
PubMed 22492049Valli 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.
PubMed 37268445Kallionpaa 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.
PubMed 32773216Kallioinen 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.
PubMed 31805854Kallionpaa 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.
PubMed 29935582Radek 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.
PubMed 29935581
Study at a glance
From the registry record, last updated by the sponsor on 11 Jan 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Neural Mechanisms of Anesthesia and Human Consciousness (LOC-2013)
- ClinicalTrials.gov ID
- NCT01889004
- Acronym / sponsor ID
- LOC-2013 / LOC-2013
- Conditions
- Consciousness, Level Altered
- Keywords
- Cerebral blood flow, Consciousness, Dexmedetomidine, EEG, Event related potentials, Functional magnetic resonance imaging, General anesthesia, Positron emission tomography
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 47 participants (actual)
- Lead sponsor
- University of TurkuUniversity, hospital or other
- Collaborators
- Academy of Finland, Hospital District of Southwestern Finland
- Study start
- Feb 2014
- Primary completion
- Jan 2016 (actual)
- Study completion
- Jan 2016 (actual)
- First posted
- 28 Jun 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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)
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Dexmedetomidine | Experimental | Drug: DexmedetomidineIntravenous dexmedetomidine using target controlled infusion |
| Propofol | Experimental | Drug: PropofolIntravenous propofol using target controlled infusion |
Who may qualify
- Ages
- 20 to 30 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Male
- Age 20-30 years
- Good general health i.e. American Society of Anesthesiologists (ASA) physical status I
- Fluent in Finnish language
- Right handedness
Key exclusion criteria (19 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DexmedetomidineAlso: DexdorEscalating concentrations until loss of responsiveness | Drug | Dexmedetomidine |
| PropofolAlso: Propofol-LipuroEscalating concentrations until loss of responsiveness | Drug | Propofol |
Primary outcome
Regional cerebral blood flow
Time frame: Several measurements during two separate days within 2 months
Altogether 14 PET scans during two separate study days. Cerebral blood flow changes will be used as surrogates for changes in regional brain activity.
3 secondary outcomes
EEG
Time frame: Continuous data collection during five separate days within 2 months
Functional magnetic resonance imaging (fMRI)
Time frame: Several measurements during one day
Event related potentials
Time frame: Several time points during five separate days within 2 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jan 2016.
- Background: PubMed 22492049Langsjo 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.
- Derived from this study: PubMed 37268445Valli 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.
- Derived from this study: PubMed 32773216Kallionpaa 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.
- Derived from this study: PubMed 31805854Kallioinen 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.
- Derived from this study: PubMed 29935582Kallionpaa 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.
- Derived from this study: PubMed 29935581Radek 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.
- Research Group Home PageLink provided by the sponsor.
Related trials for Consciousness, Level Altered
RecruitingPhase 4
The Electroencephalographic Mechanisms of Anesthesia and Human Consciousness
Consciousness, Level Altered
Not yet recruiting
Investigating Near-Threshold Perception During Ultrasonic Deep Brain Stimulation
Consciousness, Level Altered
Active, not recruitingObservational study
Intelligent Intensive Care Unit
Delirium, Confusion
Recruiting
Paired Vagus Nerve Stimulation in Mobilization of Patients With Prolonged Disorders of Consciousness
Consciousness Disorders, Brain Injury
Recruiting
REcovery From DEXmedetomidine-induced Unconsciousness
Anesthesia, Healthy
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Harry Scheinin, MD principal investigator
University of Turku
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Dexmedetomidine and Propofol in people with Consciousness, Level Altered, run by University of Turku at 1 site in Finland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Jan 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Finland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Regional cerebral blood flow (time frame: Several measurements during two separate days within 2 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01889004, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jan 2016.