Sedative OverdosePhase 1/2NCT03928366
Synchronous Effect of Anesthetics on fMRI, EEG and Clinical Responses
A Phase 1/2 study testing Propofol and Remifentanil in people with Sedative Overdose, run by Parc de Salut Mar at 1 site in Spain.
Trial summary
Background: The mechanisms of action of intravenous anesthetics are unclear and the current monitors have limitations. This signifies difficulties when assessing the correct dosage due to the considerable inter-individual variability of the patients, particularly in the elderly or seriously ill. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Sedative Overdose
- What is being tested?
- Propofol and Remifentanil
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteSpain
- Study dates
- 13 Jun 2017to 30 Jun 2021
- Phase
- Phase 1/2
- 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 18 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy adult volunteers (ASA 1 physical state) who agree to participate voluntarily in the study, previous information about it by the Principal Investigators (IP).
Who cannot join
- Psychological, psychiatric or neurological disorders. Consumption of drugs. Alterations cutaneous or anatomical cranial. Idiomatic or communication barrier. Allergy to propofol, remifentanil or to some of its excipients. Body mass index (BMI) <18 or> 30 kg / m2. Pregnancy. Airway or ventilation criteria hard. Absence of accompanying adult at the end of the study.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Synchronous Effect of Anesthetics on fMRI, EEG and Clinical Responses. Development of a More Precise System for Monitoring Anesthetic Effect.
Background: The mechanisms of action of intravenous anesthetics are unclear and the current monitors have limitations.
This signifies difficulties when assessing the correct dosage due to the considerable inter-individual variability of the patients, particularly in the elderly or seriously ill. It is necessary to customize the administration of anesthetics as underdosage can lead to the patient awareness during aggressive procedures, and over-dosage can cause serious complications and even augment mortality.
Read more
Objective: To design a new monitoring system of the levels of consciousness and analgesia in anesthetized subjects which is more accurate than those currently employed. It will be based on the synchronic changes of functional magnetic resonance (fMR) and electroencephalograph (EEG) readings, and clinical responses.
Methodology: Thirty healthy volunteers will be given propofol and remifentanil in different combinations, and painful stimuli will be also applied. The principal variable will be fMR images obtained by echo-planar imaging sequences. Real time will be correlated with cortical connectivity maps, EEG parameters (qCON, qNOX), clinical responses, and concentrations of anesthetics measured by pharmacokinetic and pharmacodynamic models (TCI).
Read the detailed description
Main goal:
Develop a system for monitoring the effect of anesthetics on consciousness and pain, based on synchronous changes in functional neuroimaging, EEG and clinical responses.
Secondary objectives:
- Analyze the changes produced in the cortical connectivity map during the induction of anesthesia to understand the process of "advancement".
- Know more accurately the neuronal circuits involved in propofol-induced sleep.
- Study if the application of a known painful stimulus modifies in any way (clinical, EEG or by RMf) the LOC that has just been reached.
- Establish propofol dosing guidelines adjusted to each patient, studying if they reach the LOC at "sedative" or "hypnotic" doses.
- Establish remifentanil dosing guidelines, adjusted to each patient, studying the concentration of remifentanil to which the pain response in neuroimaging is inhibited (activation deactivation neuronal in fMRI).
- Validate existing mathematical models in relation to plasma and brain concentrations of propofol and remifentanil.
- Validate the value of clinical signs to predict whether a patient feels the painful stimulus received.
- Conditions
- Sedative Overdose
- Being tested
- Propofol, Remifentanil
- Keywords
- Propofol, remifentanil, hypnosis, EEG, fMRI,
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PropofolDrug
Also called remifentanil
sedation
RemifentanilDrug
remifentanil
| Study group | Role | What they receive |
|---|---|---|
| Volunteers receiving propofol and remifentanil | Experimental | Volunteers receive propofol to the loss of consciousness. Then they receive remifentanil during 12 min (pain stimuli in their finger also) Receives: Drug: Propofol; Drug: Remifentanil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time and dose of propofol at loss of consciousness(LOC)
Volunteers stop tightening pneumatic pear. We register time and dose of propofol when the volunteer stops tightening pneumatic pear.
Measured: 10-15 min
Register EEG and neuroimage during remifentanil administration.
After LOC, volunteers receive increasing doses of remifentanil and painful stimuli in the nail bed. If apnea, stop infusion remifentanil Volunteers receive increasing doses of remifentanil and painful stimuli in the nail bed. If apnea, stop infusion remifentanil. We registered time, dose, saturation and breathing frequency in every volunteer.
Measured: 10-15 min
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Apr 2019
- Study start13 Jun 2017
- Primary completion9 Jan 2019
- Study completion30 Jun 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Sedative OverdoseStudies 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 1/2
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Sequential
- Model description
- Volunteers receiving propofol and then remifentanil.
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Parc de Salut Mar
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Juan Luis Fernández Candil, Parc de Salut Mar
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03928366
- Sponsor's protocol ID
- UNLOCK
- Status last verified
- Sep 2022
- First submitted
- 11 Apr 2019
- Last updated
- 30 Sep 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Participants will be introduced to the fMRI The head will be set to try to prevent involuntary movements associated with the LOC. Routine by pulse oximetry, non-invasive blood pressure and electrocardiogram (ECG). It will be administered oxygen at 2 liters / min by nasal cannula with capnography line and transcutaneous carbon dioxide will be monitored. Volunteers will not be premedicated. EEG activity and fMRI images, as detailed in the section "Study variables". Each series of acquisitions will consist of a "resting state" (rs-fMRI), in which the subject will be asked to close their eyes and leave the mind ramble without further slogans, and also a series of tasks in which the participant will be exposed to a sequence of perceptive and nociceptive stimuli in order to objectify the effect of the drug on the nervous system central. The signal extracted from the RMf images will allow to study the dynamics of the metabolic changes and neurons in the brain with a temporal resolution.
Publications
Borrat X, Ubre M, Risco R, Gambus PL, Pedroso A, Iglesias A, Fernandez-Esparrach G, Gines A, Balust J, Martinez-Palli G. Computerized tests to evaluate recovery of cognitive function after deep sedation with propofol and remifentanil for colonoscopy. J Clin Monit Comput. 2019 Feb;33(1):107-113. doi: 10.1007/s10877-018-0134-3. Epub 2018 Mar 27.
PubMed 29589170
Study at a glance
From the registry record, last updated by the sponsor on 30 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Synchronous Effect of Anesthetics on fMRI, EEG and Clinical Responses. Development of a More Precise System for Monitoring Anesthetic Effect.
- ClinicalTrials.gov ID
- NCT03928366
- Acronym / sponsor ID
- UNLOCK
- Conditions
- Sedative Overdose
- Keywords
- Propofol, remifentanil, hypnosis, EEG, fMRI,
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Parc de Salut MarUniversity, hospital or other
- Study start
- 13 Jun 2017 (actual)
- Primary completion
- 9 Jan 2019 (actual)
- Study completion
- 30 Jun 2021 (actual)
- First posted
- 26 Apr 2019 (actual)
- 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.
Background: The mechanisms of action of intravenous anesthetics are unclear and the current monitors have limitations.
This signifies difficulties when assessing the correct dosage due to the considerable inter-individual variability of the patients, particularly in the elderly or seriously ill. It is necessary to customize the administration of anesthetics as underdosage can lead to the patient awareness during aggressive procedures, and over-dosage can cause serious complications and even augment mortality.
Objective: To design a new monitoring system of the levels of consciousness and analgesia in anesthetized subjects which is more accurate than those currently employed. It will be based on the synchronic changes of functional magnetic resonance (fMR) and electroencephalograph (EEG) readings, and clinical responses.
Methodology: Thirty healthy volunteers will be given propofol and remifentanil in different combinations, and painful stimuli will be also applied. The principal variable will be fMR images obtained by echo-planar imaging sequences. Real time will be correlated with cortical connectivity maps, EEG parameters (qCON, qNOX), clinical responses, and concentrations of anesthetics measured by pharmacokinetic and pharmacodynamic models (TCI).
Detailed description
Main goal:
Develop a system for monitoring the effect of anesthetics on consciousness and pain, based on synchronous changes in functional neuroimaging, EEG and clinical responses.
Secondary objectives:
- Analyze the changes produced in the cortical connectivity map during the induction of anesthesia to understand the process of "advancement".
- Know more accurately the neuronal circuits involved in propofol-induced sleep.
- Study if the application of a known painful stimulus modifies in any way (clinical, EEG or by RMf) the LOC that has just been reached.
- Establish propofol dosing guidelines adjusted to each patient, studying if they reach the LOC at "sedative" or "hypnotic" doses.
- Establish remifentanil dosing guidelines, adjusted to each patient, studying the concentration of remifentanil to which the pain response in neuroimaging is inhibited (activation deactivation neuronal in fMRI).
- Validate existing mathematical models in relation to plasma and brain concentrations of propofol and remifentanil.
- Validate the value of clinical signs to predict whether a patient feels the painful stimulus received.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Volunteers receiving propofol and then remifentanil.
| Arm | Type | Receives |
|---|---|---|
| Volunteers receiving propofol and remifentanil | Experimental | Drug: Propofol, Drug: RemifentanilVolunteers receive propofol to the loss of consciousness. Then they receive remifentanil during 12 min (pain stimuli in their finger also) |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Healthy adult volunteers (ASA 1 physical state) who agree to participate voluntarily in the study, previous information about it by the Principal Investigators (IP).
Key exclusion criteria (1 listed)
- Psychological, psychiatric or neurological disorders. Consumption of drugs. Alterations cutaneous or anatomical cranial. Idiomatic or communication barrier. Allergy to propofol, remifentanil or to some of its excipients. Body mass index (BMI) <18 or> 30 kg / m2. Pregnancy. Airway or ventilation criteria hard. Absence of accompanying adult at the end of the study.
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 |
|---|---|---|
| PropofolAlso: remifentanilsedation | Drug | Volunteers receiving propofol and remifentanil |
| Remifentanilremifentanil | Drug | Volunteers receiving propofol and remifentanil |
Primary outcome
Time and dose of propofol at loss of consciousness(LOC)
Time frame: 10-15 min
Volunteers stop tightening pneumatic pear. We register time and dose of propofol when the volunteer stops tightening pneumatic pear.
Register EEG and neuroimage during remifentanil administration.
Time frame: 10-15 min
After LOC, volunteers receive increasing doses of remifentanil and painful stimuli in the nail bed. If apnea, stop infusion remifentanil Volunteers receive increasing doses of remifentanil and painful stimuli in the nail bed. If apnea, stop infusion remifentanil. We registered time, dose, saturation and breathing frequency in every volunteer.
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 30 Sep 2022.
- Background: PubMed 29589170Borrat X, Ubre M, Risco R, Gambus PL, Pedroso A, Iglesias A, Fernandez-Esparrach G, Gines A, Balust J, Martinez-Palli G. Computerized tests to evaluate recovery of cognitive function after deep sedation with propofol and remifentanil for colonoscopy. J Clin Monit Comput. 2019 Feb;33(1):107-113. doi: 10.1007/s10877-018-0134-3. Epub 2018 Mar 27.
- Individual participant dataSharing planned: Yes. Participants will be introduced to the fMRI The head will be set to try to prevent involuntary movements associated with the LOC. Routine by pulse oximetry, non-invasive blood pressure and electrocardiogram (ECG). It will be administered oxygen at 2 liters / min by nasal cannula with capnography line and transcutaneous carbon dioxide will be monitored. Volunteers will not be premedicated. EEG activity and fMRI images, as detailed in the section "Study variables". Each series of acquisitions will consist of a "resting state" (rs-fMRI), in which the subject will be asked to close their eyes and leave the mind ramble without further slogans, and also a series of tasks in which the participant will be exposed to a sequence of perceptive and nociceptive stimuli in order to objectify the effect of the drug on the nervous system central. The signal extracted from the RMf images will allow to study the dynamics of the metabolic changes and neurons in the brain with a temporal resolution.
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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Propofol and Remifentanil in people with Sedative Overdose, run by Parc de Salut Mar at 1 site in Spain.
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 1 inclusion and 1 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 30 Sep 2022. 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 Spain. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Time and dose of propofol at loss of consciousness(LOC) (time frame: 10-15 min). The study lists 2 primary outcomes in all. 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 NCT03928366, which also lists 1 linked publication.
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 30 Sep 2022.