AnesthesiaPhase 1MCANCT04062123
Memory & Conditioning Under Anesthesia
A Phase 1 study testing Dexmedetomidine, Propofol and Fentanyl in people with Anesthesia and Pain, run by Keith M Vogt at 1 site in United States.
Trial summary
The purpose of this study is to determine the effects of pain on long-term memory and conditioned physiologic responses in the presence and absence of distinct intravenous anesthetics. Read more about this study
- Who is it for?
- Ages 18 to 39 yearsHealthy volunteers can take part
- Conditions the study is for
- Anesthesia, Pain
- What is being tested?
- Dexmedetomidine, Propofol and Fentanyl
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 92 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Jul 2020to 22 Apr 2024
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 39 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Adults, age 18-39, who are native English speakers with at least a high school education
- have normal hearing and memory
- be of normal body-weight
- be generally healthy (free from significant chronic disease)
- have none of the specific exclusion criteria
- have a valid email address and valid phone number throughout the study
- anticipate ability to participate in all visits required for the phase of the study in which they are enrolled
Who cannot join
- Pregnancy
- Body mass index > 35 (obese) or < 18 (underweight)
- Use of psychotropic medications, including anti-epileptics, anti-psychotics, anxiolytics, anti-depressants, stimulants, sleep-aids, anti-histamines, or analgesics
- History of adverse reaction to OR abuse of: dexmedetomidine (Precedex), propofol (Diprivan) or the opioids class of medications (fentanyl, morphine, hydromorphone, etc)
- History of clinically significant memory or hearing loss
- History of obstructive sleep apnea
Show all 15Show fewer
- History of neurologic or psychiatric disease, including benign tremor
- History of significant cardiac disease, including high blood pressure or arrhythmia
- History of significant pulmonary disease
- History of diabetes or neuropathy
- History of chronic pain, or other pain processing disorder
- Have an implanted medical electronic device
- Have indwelling or implanted metal in their body that is not MRI-compatible
- Have claustrophobia
- Have a history of drug abuse
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15213
About this study
Official title: Modulation of Memory and Conditioning by Pain During Sedation With Anesthetics
The purpose of this study is to determine the effects of pain on long-term memory and conditioned physiologic responses in the presence and absence of distinct intravenous anesthetics. Functional magnetic resonance imaging will be used to identify the neural correlates of these phenomena The study will occur over 5 visits and involves no long-term follow up.
Read the detailed description
Purpose: Sedative-hypnotic and analgesic agents (termed "anesthetics") are routinely used during medical procedures to prevent or ease suffering, suppressing the conscious experience of pain and its encoding into memory. While overt awareness under general anesthesia is a rare clinical event, implicit memory may still form. Further, at sub-hypnotic anesthetic doses, animals show enhanced fear conditioning and humans may have enhanced amygdala activity. This motivates the investigator's study, as poorly-contextualized aversive memories are theorized to initiate anxiety-spectrum disorders, which may explain the high incidence of post-traumatic stress disorder after anesthetic awareness.
Objective: How anesthetics facilitate or inhibit poorly-contextualized aversive memories is incompletely understood, with little mechanistic work done in human subjects. Thus, there is a critical need to understand how anesthetics modulate the memory and threat response systems during painful stimulation. The overall scientific objective is to determine the memory-modulating effects of propofol, dexmedetomidine, and fentanyl in the context of periodic painful stimulation.
Aim 1: Determine how behavioral and physiologic measures of memory are modulated by pain and the individual effects of three pharmacologically distinct drugs: propofol, dexmedetomidine, and fentanyl. Hypotheses: Based on previous results, 1a) explicit memory will be significantly reduced by propofol and dexmedetomidine, but only modestly by fentanyl. Consistent with my preliminary data, 1b) priming effects will be seen for pain-paired words under all drugs. Electrodermal activity changes still occur with opioids and propofol, thus 1c) pain-related physiologic responses will persist with these two drugs but be blunted by the anti-adrenergic effect of dexmedetomidine.
Aim 2: Determine the brain structures differentially engaged in memory encoding under pain and drug conditions. Task-related functional magnetic resonance imaging (MRI) activity for behavioral measures of explicit or implicit memory will be determined, comparing pain-paired vs non-pain items across drug and no-drug datasets. Functional connectivity (FC) MRI (fcMRI) will be compared between task and drug conditions. The entire brain will be explored, but predictions for key structures follow. Hypotheses: 2a) Hippocampal activity, will be blunted by propofol and dexmedetomidine, while fentanyl will have minimal effect. 2b) Amygdala activity, responsible for physiologic responses, will parallel the predictions in 1c across drug and pain conditions. 2c) Insula activity will be greater for pain-paired items, and this will be attenuated by fentanyl > dexmedetomidine > propofol, corresponding to their anticipated analgesic effect. 2d) Pain has been shown to affect fcMRI during a cognitive task, and thus FC between the key regions in 2a-c will be reduced by all three drugs, in characteristic patterns.
- Conditions
- Anesthesia, Pain
- Being tested
- Dexmedetomidine, Propofol, Fentanyl, Peripheral Nerve Stimulation, Placebo
- Keywords
- propofol, dexmedetomidine, fentanyl, functional MRI, electric nerve stimulation, sedation, functional connectivity
- Medical subject headings
- Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DexmedetomidineDrug
Also called Precedex
Subjects in this group will receive a intravenous infusion of this drug, during a portion of the study. Dose will be targeted to a brain effect site concentration of 0.15 ng/ml, using pharmacokinetic modelling within the STANPUMP algorithm that accounts for subject's age, gender, height, \& weight.
PropofolDrug
Also called Diprivan
Subjects in this group will receive a intravenous infusion of this drug, during a portion of the study. Dose will be targeted to a brain effect site concentration of 0.7 mcg/ml, using pharmacokinetic modelling within the STANPUMP algorithm that accounts for subject's age, gender, height, \& weight.
FentanylDrug
Also called fentanyl citrate
Subjects in this group will receive a intravenous infusion of this drug, during a portion of the study. Dose will be targeted to a brain effect site concentration of 0.9 ng/ml, using pharmacokinetic modelling within the STANPUMP algorithm that accounts for subject's age, gender, height, \& weight.
Peripheral Nerve StimulationDevice
Also called Electric Nerve Stimulation
Experimental acute pain stimulus will be delivered using a nerve stimulator. These painful shocks will be paired randomly with some of the experimental cues.
PlaceboDrug
Also called saline, IV fluid
Crystalloid IV solution will be infused, with no active drug.
| Study group | Role | What they receive |
|---|---|---|
| Dexmedetomidine | Experimental | Subjects in this group will receive dexmedetomidine during the drug portion of the experiment. Receives: Drug: Dexmedetomidine; Device: Peripheral Nerve Stimulation; Drug: Placebo |
| Propofol | Experimental | Subjects in this group will receive propofol during the drug portion of the experiment. Receives: Drug: Propofol; Device: Peripheral Nerve Stimulation; Drug: Placebo |
| Fentanyl | Experimental | Subjects in this group will receive fentanyl during the drug portion of the experiment. Receives: Drug: Fentanyl; Device: Peripheral Nerve Stimulation; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Explicit Memory Performance
Recognition memory testing, using the Remember-Know procedure, in which subjects indicate whether they recognize previously experienced experimental items among novel items (not previously in the experiment). This allows calculation of interdependent measures of recollection \& familiarity using the signal detection statistic, d'. d' is calculated as the cumulative Gaussian distribution of false positive responses subtracted from the cumulative Gaussian distribution of correctly identified previously-experienced items. d' is on a (theoretically infinite) scale of standard deviation units, with negative values representing performance worse than chance guessing and positive values representing stand deviations of performance above chance.
Measured: 24-hrs post-experiment
Secondary outcomes (3)
Brain Activation in the Hippocampus for Successful Memory Formation: Placebo Condition Minus Drug Condition
The Z-score is calculated by linear regression of the task timing against the MRI signal time-course (MRI data is in arbitrary units with no maximum or minimum) at each voxel (single data point in brain). The outcome is listed for the hippocampus, but similar scores are calculated throughout the brain. Z-score of 0 indicates no task-related changes. Z-scores further from zero indicate a larger difference in brain activity, with positive values indicating decreases under the drug condition, while negative Z-scores indicate increases under drug, compared to control. This outcome is reported as a number, as it is calculated using all the data across subjects combined into one statistical measure for the overall strength of difference in MRI signal change between two groups of data. Dispersion measures cannot be calculated for the summary Z-score.
Measured: Immediately after each experimental item
Heart Rate Response
Heart rate changes (measured by electrocardiogram, EKG) were planned to be determined following experimental stimuli that delivered as part of the experiment. A 1-6 second window of physiologic data will be analyzed for changes in the peak of the EKG response (R-wave), allowing calculation of instantaneous heart rate. Increases in heart rate are well-known to correlate to sympathetic nervous system activity increases.
Measured: Immediately after each experimental item
Skin Response
Electrodermal activity (galvanic skin) response was planned to be determined following experimental stimuli that delivered as part of the experiment. A 1-6 second window of physiologic data will be analyzed for changes in electrodermal activity, measured from the palm of subjects' hand. this well-established measure indicates sweat gland activity and is correlated to sympathetic nervous system activity increases.
Measured: Immediately after each experimental item
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Aug 2019
- Study start30 Jul 2020
- Primary completion22 Apr 2024
- Study completion22 Apr 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for AnesthesiaStudies 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
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Placebo-controlled, within-subject, crossover between no-drug and assigned drug (in randomized order)
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 92 participants (actual)
Sponsor and investigators
- Lead sponsor
- Keith M Vogt
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of General Medical Sciences (NIGMS)
- Responsible party
- Sponsor-investigator, Keith M Vogt, University of Pittsburgh
- Investigators
- Keith M Vogt, MD, PhD, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04062123
- Sponsor's protocol ID
- STUDY19030183
- Other IDs
- R35GM146822
- Acronym
- MCA
- Status last verified
- Mar 2025
- First submitted
- 11 Jul 2019
- Last updated
- 18 Apr 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Modulation of Memory and Conditioning by Pain During Sedation With Anesthetics
- ClinicalTrials.gov ID
- NCT04062123
- Acronym / sponsor ID
- MCA / STUDY19030183
- Conditions
- Anesthesia, Pain
- Keywords
- propofol, dexmedetomidine, fentanyl, functional MRI, electric nerve stimulation, sedation, functional connectivity
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 92 participants (actual)
- Lead sponsor
- Keith M VogtUniversity, hospital or other
- Collaborators
- National Institute of General Medical Sciences (NIGMS)
- Study start
- 30 Jul 2020 (actual)
- Primary completion
- 22 Apr 2024 (actual)
- Study completion
- 22 Apr 2024 (actual)
- First posted
- 20 Aug 2019 (actual)
- Results
- Posted 18 Apr 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine the effects of pain on long-term memory and conditioned physiologic responses in the presence and absence of distinct intravenous anesthetics. Functional magnetic resonance imaging will be used to identify the neural correlates of these phenomena The study will occur over 5 visits and involves no long-term follow up.
Detailed description
Purpose: Sedative-hypnotic and analgesic agents (termed "anesthetics") are routinely used during medical procedures to prevent or ease suffering, suppressing the conscious experience of pain and its encoding into memory. While overt awareness under general anesthesia is a rare clinical event, implicit memory may still form. Further, at sub-hypnotic anesthetic doses, animals show enhanced fear conditioning and humans may have enhanced amygdala activity. This motivates the investigator's study, as poorly-contextualized aversive memories are theorized to initiate anxiety-spectrum disorders, which may explain the high incidence of post-traumatic stress disorder after anesthetic awareness.
Objective: How anesthetics facilitate or inhibit poorly-contextualized aversive memories is incompletely understood, with little mechanistic work done in human subjects. Thus, there is a critical need to understand how anesthetics modulate the memory and threat response systems during painful stimulation. The overall scientific objective is to determine the memory-modulating effects of propofol, dexmedetomidine, and fentanyl in the context of periodic painful stimulation.
Aim 1: Determine how behavioral and physiologic measures of memory are modulated by pain and the individual effects of three pharmacologically distinct drugs: propofol, dexmedetomidine, and fentanyl. Hypotheses: Based on previous results, 1a) explicit memory will be significantly reduced by propofol and dexmedetomidine, but only modestly by fentanyl. Consistent with my preliminary data, 1b) priming effects will be seen for pain-paired words under all drugs. Electrodermal activity changes still occur with opioids and propofol, thus 1c) pain-related physiologic responses will persist with these two drugs but be blunted by the anti-adrenergic effect of dexmedetomidine.
Aim 2: Determine the brain structures differentially engaged in memory encoding under pain and drug conditions. Task-related functional magnetic resonance imaging (MRI) activity for behavioral measures of explicit or implicit memory will be determined, comparing pain-paired vs non-pain items across drug and no-drug datasets. Functional connectivity (FC) MRI (fcMRI) will be compared between task and drug conditions. The entire brain will be explored, but predictions for key structures follow. Hypotheses: 2a) Hippocampal activity, will be blunted by propofol and dexmedetomidine, while fentanyl will have minimal effect. 2b) Amygdala activity, responsible for physiologic responses, will parallel the predictions in 1c across drug and pain conditions. 2c) Insula activity will be greater for pain-paired items, and this will be attenuated by fentanyl > dexmedetomidine > propofol, corresponding to their anticipated analgesic effect. 2d) Pain has been shown to affect fcMRI during a cognitive task, and thus FC between the key regions in 2a-c will be reduced by all three drugs, in characteristic patterns.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 3
- Model description
- Placebo-controlled, within-subject, crossover between no-drug and assigned drug (in randomized order)
| Arm | Type | Receives |
|---|---|---|
| Dexmedetomidine | Experimental | Drug: Dexmedetomidine, Device: Peripheral Nerve Stimulation, Drug: PlaceboSubjects in this group will receive dexmedetomidine during the drug portion of the experiment. |
| Propofol | Experimental | Drug: Propofol, Device: Peripheral Nerve Stimulation, Drug: PlaceboSubjects in this group will receive propofol during the drug portion of the experiment. |
| Fentanyl | Experimental | Drug: Fentanyl, Device: Peripheral Nerve Stimulation, Drug: PlaceboSubjects in this group will receive fentanyl during the drug portion of the experiment. |
Who may qualify
- Ages
- 18 to 39 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Adults, age 18-39, who are native English speakers with at least a high school education
- have normal hearing and memory
- be of normal body-weight
- be generally healthy (free from significant chronic disease)
- have none of the specific exclusion criteria
Key exclusion criteria (15 listed)
- Pregnancy
- Body mass index > 35 (obese) or < 18 (underweight)
- Use of psychotropic medications, including anti-epileptics, anti-psychotics, anxiolytics, anti-depressants, stimulants, sleep-aids, anti-histamines, or analgesics
- History of adverse reaction to OR abuse of: dexmedetomidine (Precedex), propofol (Diprivan) or the opioids class of medications (fentanyl, morphine, hydromorphone, etc)
- History of clinically significant memory or hearing loss
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: PrecedexSubjects in this group will receive a intravenous infusion of this drug, during a portion of the study. Dose will be targeted to a brain effect site concentration of 0.15 ng/ml, using pharmacokinetic modelling within the STANPUMP algorithm that accounts for subject's age, gender, height, \& weight. | Drug | Dexmedetomidine |
| PropofolAlso: DiprivanSubjects in this group will receive a intravenous infusion of this drug, during a portion of the study. Dose will be targeted to a brain effect site concentration of 0.7 mcg/ml, using pharmacokinetic modelling within the STANPUMP algorithm that accounts for subject's age, gender, height, \& weight. | Drug | Propofol |
| FentanylAlso: fentanyl citrateSubjects in this group will receive a intravenous infusion of this drug, during a portion of the study. Dose will be targeted to a brain effect site concentration of 0.9 ng/ml, using pharmacokinetic modelling within the STANPUMP algorithm that accounts for subject's age, gender, height, \& weight. | Drug | Fentanyl |
| Peripheral Nerve StimulationAlso: Electric Nerve StimulationExperimental acute pain stimulus will be delivered using a nerve stimulator. These painful shocks will be paired randomly with some of the experimental cues. | Device | Dexmedetomidine, Fentanyl, Propofol |
| PlaceboAlso: saline, IV fluidCrystalloid IV solution will be infused, with no active drug. | Drug | Dexmedetomidine, Fentanyl, Propofol |
Primary outcome
Explicit Memory Performance
Time frame: 24-hrs post-experiment
Recognition memory testing, using the Remember-Know procedure, in which subjects indicate whether they recognize previously experienced experimental items among novel items (not previously in the experiment). This allows calculation of interdependent measures of recollection \& familiarity using the signal detection statistic, d'. d' is calculated as the cumulative Gaussian distribution of false positive responses subtracted from the cumulative Gaussian distribution of correctly identified previously-experienced items. d' is on a (theoretically infinite) scale of standard deviation units, with negative values representing performance worse than chance guessing and positive values representing stand deviations of performance above chance.
3 secondary outcomes
Brain Activation in the Hippocampus for Successful Memory Formation: Placebo Condition Minus Drug Condition
Time frame: Immediately after each experimental item
Heart Rate Response
Time frame: Immediately after each experimental item
Skin Response
Time frame: Immediately after each experimental item
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Apr 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Keith M Vogt, MD, PhD principal investigator
University of Pittsburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Dexmedetomidine, Propofol and Fentanyl in people with Anesthesia and Pain, run by Keith M Vogt at 1 site in United States.
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 15 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 18 Apr 2025. 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 United States. 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Apr 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Explicit Memory Performance (time frame: 24-hrs post-experiment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 18 Apr 2025.