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Clinical Trials/NCT02515890
NCT02515890
Completed
Phase 1

Modulation of Long-term Memory by the Experience of Pain During Sedation With Anesthetics

University of Pittsburgh1 site in 1 country32 target enrollmentNovember 19, 2015

Overview

Phase
Phase 1
Intervention
Ketamine
Conditions
Amnesia
Sponsor
University of Pittsburgh
Enrollment
32
Locations
1
Primary Endpoint
Memory Testing
Status
Completed
Last Updated
5 years ago

Overview

Brief 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. 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.

Registry
clinicaltrials.gov
Start Date
November 19, 2015
End Date
December 12, 2018
Last Updated
5 years ago
Study Type
Interventional
Study Design
Crossover
Sex
All

Investigators

Responsible Party
Principal Investigator
Principal Investigator

Keith M. Vogt, MD, PhD

Assistant Professor

University of Pittsburgh

Eligibility Criteria

Inclusion Criteria

  • Healthy adult volunteers, with normal memory and hearing, whose native language is English

Exclusion Criteria

  • 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

Arms & Interventions

Ketamine Only

All subjects receive saline (control), followed by ketamine infusion. They also experience intermittent experimental pain delivered by peripheral nerve stimulation.

Intervention: Ketamine

Dexmedetomidine Only

All subjects receive saline (control), followed by a dexmedetomidine infusion. They also experience intermittent experimental pain delivered by peripheral nerve stimulation.

Intervention: Dexmedetomidine

Dexmedetomidine Only

All subjects receive saline (control), followed by a dexmedetomidine infusion. They also experience intermittent experimental pain delivered by peripheral nerve stimulation.

Intervention: Peripheral nerve stimulation

Midazolam Only

Subjects receive saline (control), followed by midazolam infusion. They also experience intermittent experimental pain delivered by peripheral nerve stimulation.

Intervention: Midazolam

Midazolam Only

Subjects receive saline (control), followed by midazolam infusion. They also experience intermittent experimental pain delivered by peripheral nerve stimulation.

Intervention: Peripheral nerve stimulation

Ketamine Only

All subjects receive saline (control), followed by ketamine infusion. They also experience intermittent experimental pain delivered by peripheral nerve stimulation.

Intervention: Peripheral nerve stimulation

Saline/Midazolam/Saline/Ketamine

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.

Intervention: Midazolam

Saline/Midazolam/Saline/Ketamine

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.

Intervention: Peripheral nerve stimulation

Saline/Midazolam/Saline/Ketamine

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.

Intervention: Ketamine

Saline/Ketamine/Saline/Midazolam

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.

Intervention: Midazolam

Saline/Ketamine/Saline/Midazolam

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.

Intervention: Peripheral nerve stimulation

Saline/Ketamine/Saline/Midazolam

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.

Intervention: Ketamine

Outcomes

Primary Outcomes

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.

Study Sites (1)

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