AmnesiaPhase 1MMANCT02515890
Memory Modulation by Pain During Anesthesia
A Phase 1 study testing Dexmedetomidine, Midazolam and Peripheral nerve stimulation in people with Amnesia and Pain, run by University of Pittsburgh at 1 site in United States.
Trial summary
The purpose of this study is to determine the effects of pain on facilitating long-term auditory memory in the presence and absence of distinct intravenous anesthetics. The ability to identify previously presented words from a list assessed the degree of memory formation. Read more about this study
- Who is it for?
- Ages 18 to 39 yearsHealthy volunteers can take part
- Conditions the study is for
- Amnesia, Pain, Anesthesia
- What is being tested?
- Dexmedetomidine, Midazolam and Peripheral nerve stimulation
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Nov 2015to 12 Dec 2018
- 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
- Healthy adult volunteers, with normal memory and hearing, whose native language is English
Who cannot join
- pregnancy
- significant memory or hearing loss
- sleep apnea
- chronic pain
- metal or electronic implants
- claustrophobia
- Currently taking: antidepressants, anti-psychotics, antihistamines, anti-anxiety medication, stimulants, sleep-aids, or pain medication
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pittsburgh
Pittsburgh, Pennsylvania, 15213
About this study
Official title: Modulation of Long-term Memory by the Experience of Pain During Sedation With Anesthetics
The purpose of this study is to determine the effects of pain on facilitating long-term auditory memory in the presence and absence of distinct intravenous anesthetics. The ability to identify previously presented words from a list assessed the degree of memory formation. In a subset of subjects, functional magnetic resonance imaging was used to identify the neural correlates of memory inhibition or facilitation by the combination of pain and anesthetic used.
Read the detailed description
This study adds specific details to the current incomplete body of knowledge examining the effect of pain on memory formation under the influence of anesthetic agents.
Pain and anesthetic agents were administered as experimental variables in this study. Healthy adult subjects were played repeated lists of words and performed several decision-making tasks that encourage memory encoding. Some words were consistently paired with painful electric shock, and was anticipated to improve subsequent memory performance specifically for those items. The same experiment was repeated in all subjects during the administration of 1-2 possible agents that reduce memory formation: dexmedetomidine, a predominantly sedative agent, and midazolam, a well-known amnestic agent, and ketamine, a well-known dissociative analgo-sedative. The extent to which pain modulates memory performance under the effects of the anesthetic agents was the primary outcome of interest.
Further, a subset of the subjects performed the same experimental procedures while undergoing functional magnetic resonance imaging, which continuously reflects neuronal activity throughout the brain. Classic memory areas were predicted to be activated by the auditory processing task, but how these neural circuits change under the two anesthetic agents with the concomitant experience of pain were of interest. It was anticipated that pain recruits a parallel memory pathway using limbic structures, known for their involvement in fear conditioning. Additionally, stronger and more diffuse cortical processing likely occurs with concomitant pain, as level of sedation was reduced by this strong stimulus. Discovering the anatomic correlates specific to each experimental variable (pain and anesthetic), and their interplay, may help refine our model of brain function during the dynamics of pain and sedation.
- Conditions
- Amnesia, Pain, Anesthesia
- Being tested
- Dexmedetomidine, Midazolam, Peripheral nerve stimulation, Ketamine
- Keywords
- midazolam, dexmedetomidine, memory, ketamine
- Medical subject headings
- Amnesia, Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DexmedetomidineDrug
Also called Precedex
Selected subjects received this drug during a portion of the study
MidazolamDrug
Also called Versed
Selected subjects received this drug during a portion of the study
Peripheral nerve stimulationDevice
Also called electric nerve stimulation
Experimental acute pain stimulus was delivered using a nerve stimulator. These painful shocks were paired randomly with some of the auditory experimental cues.
KetamineDrug
Also called Ketalar
Selected subjects received this drug during a portion of the study
| Study group | Role | What they receive |
|---|---|---|
| Dexmedetomidine Only | Experimental | All subjects receive saline (control), followed by a dexmedetomidine infusion. They also experience intermittent experimental pain delivered by peripheral nerve stimulation. Receives: Drug: Dexmedetomidine; Device: Peripheral nerve stimulation |
| Midazolam Only | Experimental | Subjects receive saline (control), followed by midazolam infusion. They also experience intermittent experimental pain delivered by peripheral nerve stimulation. Receives: Drug: Midazolam; Device: Peripheral nerve stimulation |
| Ketamine Only | Experimental | All subjects receive saline (control), followed by ketamine infusion. They also experience intermittent experimental pain delivered by peripheral nerve stimulation. Receives: Device: Peripheral nerve stimulation; Drug: Ketamine |
| Saline/Midazolam/Saline/Ketamine | Experimental | All subjects receive saline (control), followed by midazolam infusion. They also experience intermittent experimental pain delivered by peripheral nerve stimulation.
Subjects then returned at least 1 week later for another set of experimental sessions with the same design, however the saline was followed by ketamine infusion. Receives: Drug: Midazolam; Device: Peripheral nerve stimulation; Drug: Ketamine |
| Saline/Ketamine/Saline/Midazolam | Experimental | All subjects receive saline (control), followed by ketamine infusion. They also experience intermittent experimental pain delivered by peripheral nerve stimulation.
Subjects then returned at least 1 week later for another set of experimental sessions with the same design, however the saline was followed by midazolam infusion. Receives: Drug: Midazolam; Device: Peripheral nerve stimulation; Drug: Ketamine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Memory Testing
Subjects completed the Remember, Know, New (RKN) task during next day testing. Their d' memory score was calculated based on their ability to discriminate between previously heard words and new words. A higher d' score indicates stronger recollection. D' scores were compared across the control condition (saline) and the drug conditions dexmedetomidine, midazolam, and ketamine. Performance was also calculated according to words associated with Pain and No Pain conditions.
Measured: At memory testing 1 day later
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Aug 2015 (estimated)
- Study start19 Nov 2015
- Primary completion12 Dec 2018
- Study completion12 Dec 2018
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 AmnesiaStudies of the same condition, open and under way.
- More trials run by University of PittsburghThe sponsor's other registered studies.
- 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
- Crossover
- Model description
- There are 3 single drug arms completed by a few participants. The majority of participants participated in a crossover design with two drugs, midazolam \& ketamine.
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pittsburgh
- Sponsor type
- University, hospital or other
- Collaborators
- Foundation for Anesthesia Education and Research
- Responsible party
- Principal investigator, Keith M. Vogt, MD, PhD, University of Pittsburgh
- Investigators
- Keith M Vogt, MD, PhD, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02515890
- Sponsor's protocol ID
- PRO14050609
- Acronym
- MMA
- Status last verified
- Jun 2020
- First submitted
- 3 Aug 2015
- Last updated
- 1 Jul 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- Yes: Data will be published. After all analysis and dissemination is complete, functional images will be shared via data repository.
Study at a glance
From the registry record, last updated by the sponsor on 1 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Modulation of Long-term Memory by the Experience of Pain During Sedation With Anesthetics
- ClinicalTrials.gov ID
- NCT02515890
- Acronym / sponsor ID
- MMA / PRO14050609
- Conditions
- Amnesia, Pain, Anesthesia
- Keywords
- midazolam, dexmedetomidine, memory, ketamine
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- University of PittsburghUniversity, hospital or other
- Collaborators
- Foundation for Anesthesia Education and Research
- Study start
- 19 Nov 2015 (actual)
- Primary completion
- 12 Dec 2018 (actual)
- Study completion
- 12 Dec 2018 (actual)
- First posted
- 5 Aug 2015 (estimated)
- Results
- Posted 1 Jul 2020
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 facilitating long-term auditory memory in the presence and absence of distinct intravenous anesthetics. The ability to identify previously presented words from a list assessed the degree of memory formation. In a subset of subjects, functional magnetic resonance imaging was used to identify the neural correlates of memory inhibition or facilitation by the combination of pain and anesthetic used.
Detailed description
This study adds specific details to the current incomplete body of knowledge examining the effect of pain on memory formation under the influence of anesthetic agents.
Pain and anesthetic agents were administered as experimental variables in this study. Healthy adult subjects were played repeated lists of words and performed several decision-making tasks that encourage memory encoding. Some words were consistently paired with painful electric shock, and was anticipated to improve subsequent memory performance specifically for those items. The same experiment was repeated in all subjects during the administration of 1-2 possible agents that reduce memory formation: dexmedetomidine, a predominantly sedative agent, and midazolam, a well-known amnestic agent, and ketamine, a well-known dissociative analgo-sedative. The extent to which pain modulates memory performance under the effects of the anesthetic agents was the primary outcome of interest.
Further, a subset of the subjects performed the same experimental procedures while undergoing functional magnetic resonance imaging, which continuously reflects neuronal activity throughout the brain. Classic memory areas were predicted to be activated by the auditory processing task, but how these neural circuits change under the two anesthetic agents with the concomitant experience of pain were of interest. It was anticipated that pain recruits a parallel memory pathway using limbic structures, known for their involvement in fear conditioning. Additionally, stronger and more diffuse cortical processing likely occurs with concomitant pain, as level of sedation was reduced by this strong stimulus. Discovering the anatomic correlates specific to each experimental variable (pain and anesthetic), and their interplay, may help refine our model of brain function during the dynamics of pain and sedation.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 5
- Model description
- There are 3 single drug arms completed by a few participants. The majority of participants participated in a crossover design with two drugs, midazolam \& ketamine.
| Arm | Type | Receives |
|---|---|---|
| Dexmedetomidine Only | Experimental | Drug: Dexmedetomidine, Device: Peripheral nerve stimulationAll subjects receive saline (control), followed by a dexmedetomidine infusion. They also experience intermittent experimental pain delivered by peripheral nerve stimulation. |
| Midazolam Only | Experimental | Drug: Midazolam, Device: Peripheral nerve stimulationSubjects receive saline (control), followed by midazolam infusion. They also experience intermittent experimental pain delivered by peripheral nerve stimulation. |
| Ketamine Only | Experimental | Device: Peripheral nerve stimulation, Drug: KetamineAll subjects receive saline (control), followed by ketamine infusion. They also experience intermittent experimental pain delivered by peripheral nerve stimulation. |
| Saline/Midazolam/Saline/Ketamine | Experimental | Drug: Midazolam, Device: Peripheral nerve stimulation, Drug: KetamineAll subjects receive saline (control), followed by midazolam infusion. They also experience intermittent experimental pain delivered by peripheral nerve stimulation. Subjects then returned at least 1 week later for another set of experimental sessions with the same design, however the saline was followed by ketamine infusion. |
| Saline/Ketamine/Saline/Midazolam | Experimental | Drug: Midazolam, Device: Peripheral nerve stimulation, Drug: KetamineAll subjects receive saline (control), followed by ketamine infusion. They also experience intermittent experimental pain delivered by peripheral nerve stimulation. Subjects then returned at least 1 week later for another set of experimental sessions with the same design, however the saline was followed by midazolam infusion. |
Who may qualify
- Ages
- 18 to 39 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Healthy adult volunteers, with normal memory and hearing, whose native language is English
Key exclusion criteria (7 listed)
- pregnancy
- significant memory or hearing loss
- sleep apnea
- chronic pain
- metal or electronic implants
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: PrecedexSelected subjects received this drug during a portion of the study | Drug | Dexmedetomidine Only |
| MidazolamAlso: VersedSelected subjects received this drug during a portion of the study | Drug | Midazolam Only, Saline/Ketamine/Saline/Midazolam, Saline/Midazolam/Saline/Ketamine |
| Peripheral nerve stimulationAlso: electric nerve stimulationExperimental acute pain stimulus was delivered using a nerve stimulator. These painful shocks were paired randomly with some of the auditory experimental cues. | Device | Dexmedetomidine Only, Ketamine Only, Midazolam Only, Saline/Ketamine/Saline/Midazolam, Saline/Midazolam/Saline/Ketamine |
| KetamineAlso: KetalarSelected subjects received this drug during a portion of the study | Drug | Ketamine Only, Saline/Ketamine/Saline/Midazolam, Saline/Midazolam/Saline/Ketamine |
Primary outcome
Memory Testing
Time frame: At memory testing 1 day later
Subjects completed the Remember, Know, New (RKN) task during next day testing. Their d' memory score was calculated based on their ability to discriminate between previously heard words and new words. A higher d' score indicates stronger recollection. D' scores were compared across the control condition (saline) and the drug conditions dexmedetomidine, midazolam, and ketamine. Performance was also calculated according to words associated with Pain and No Pain conditions.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jul 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. Data will be published. After all analysis and dissemination is complete, functional images will be shared via data repository.
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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, Midazolam and Peripheral nerve stimulation in people with Amnesia and Pain, run by University of Pittsburgh 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 1 inclusion and 7 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 1 Jul 2020. 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 1 Jul 2020). 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?
Memory Testing (time frame: At memory testing 1 day later). 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 1 Jul 2020.