Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Memory Modulation by Pain During Anesthesia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02515890
Recruitment Status : Active, not recruiting
First Posted : August 5, 2015
Last Update Posted : December 17, 2018
Sponsor:
Information provided by (Responsible Party):
Keith M. Vogt, MD, PhD, University of Pittsburgh

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 will asses the degree of memory formation. In a subset of subjects, functional magnetic resonance imaging will be used to identify the neural correlates of memory inhibition or facilitation by the combination of pain and anesthetic used. The primary hypothesis is that pain will enhance memory formation, and that this will be mediated by additional neural pathways compared to those used to encode words not paired with pain. The study will occur over 4-5 visits and involves no long-term follow up.

Condition or disease Intervention/treatment Phase
Amnesia Pain Anesthesia Drug: Dexmedetomidine Drug: Midazolam Device: Peripheral nerve stimulation Drug: Ketamine Not Applicable

Detailed Description:

This study will add specific details to the current incomplete body of knowledge examining the effect of pain on memory formation under the influence of anesthetic agents. Pain is common during surgery, and preventing memory during such procedures is a fundamental goal of anesthetic care, as awareness under anesthesia can cause life-long psychiatric disturbance. However, currently available monitors cannot always detect when a patient is at risk for awareness or memory under anesthesia. This is largely due to an incomplete description of the circumstances that favor memory formation versus those that effectively inhibit it.

Pain and anesthetic agents will be administered as experimental variables in this study. Healthy adult subjects will be played repeated lists of words and perform several decision-making tasks that encourage memory encoding. Some words will be consistently paired with painful electric shock, and this is anticipated to improve subsequent memory performance specifically for those items. The same experiment will be repeated in all subjects during the administration of two agents that reduce memory formation: dexmedetomidine, a predominantly sedative agent, and midazolam, a well-known amnestic agent. The extent to which pain modulates the sedative and amnestic effects of the anesthetic agents will be the primary outcome of interest. Psychometric testing for stress, anxiety, depression, and sleepiness will be performed in the subjects, and regression analysis will be used to determine which of these may explain the commonly observed inter-individual response variability to pharmacologic sedation and amnesia.

Further, a subset of the subjects will perform the same experimental procedures while undergoing functional magnetic resonance imaging, which will continuously reflect neuronal activity throughout the brain. Classic memory areas are 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 will be of interest. It is anticipated that pain will recruit a parallel memory pathway using limbic structures, known for their involvement in fear conditioning. Additionally, stronger and more diffuse cortical processing will likely occur with concomitant pain, as level of sedation will be reduced by this strong stimulus. Discovering the anatomic correlates specific to each experimental variable (pain and anesthetic), and their interplay, will refine the investigators' model of brain function during the dynamics of surgery and may someday allow more predictive monitoring.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single (Participant)
Primary Purpose: Basic Science
Official Title: Modulation of Long-term Memory by the Experience of Pain During Sedation With Anesthetics
Study Start Date : August 2015
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Memory

Arm Intervention/treatment
Experimental: Drug protocol A (single drug)
All subjects will receive either midazolam, dexmedetomidine, or ketamine, on separate visits. in randomized fashion. They will also experience intermittent experimental pain delivered by peripheral nerve stimulation.
Drug: Dexmedetomidine
Subjects will receive this drug during a portion of the study
Other Name: Precedex

Drug: Midazolam
Subjects will receive this drug during a portion of the study
Other Name: Versed

Device: Peripheral nerve stimulation
Experimental acute pain stimulus will be delivered using a nerve stimulator. These painful shocks will be paired randomly with some of the auditory experimental cues.
Other Name: electric nerve stimulation

Drug: Ketamine
Subjects will receive this drug during a portion of the study
Other Name: Ketalar

Experimental: Drug protocol B (two drugs)
All subjects will receive one drug followed by another, on separate visits, in randomized fashion. They will also experience intermittent experimental pain delivered by peripheral nerve stimulation.
Drug: Dexmedetomidine
Subjects will receive this drug during a portion of the study
Other Name: Precedex

Drug: Midazolam
Subjects will receive this drug during a portion of the study
Other Name: Versed

Device: Peripheral nerve stimulation
Experimental acute pain stimulus will be delivered using a nerve stimulator. These painful shocks will be paired randomly with some of the auditory experimental cues.
Other Name: electric nerve stimulation

Drug: Ketamine
Subjects will receive this drug during a portion of the study
Other Name: Ketalar

Experimental: Drug protocol C (all 3 drugs)
Subjects will receive all 3 drugs, in randomized fashion, across separate study visits. They will also experience intermittent experimental pain delivered by peripheral nerve stimulation.
Drug: Dexmedetomidine
Subjects will receive this drug during a portion of the study
Other Name: Precedex

Drug: Midazolam
Subjects will receive this drug during a portion of the study
Other Name: Versed

Device: Peripheral nerve stimulation
Experimental acute pain stimulus will be delivered using a nerve stimulator. These painful shocks will be paired randomly with some of the auditory experimental cues.
Other Name: electric nerve stimulation

Drug: Ketamine
Subjects will receive this drug during a portion of the study
Other Name: Ketalar




Primary Outcome Measures :
  1. Number of words recalled, by memory testing [ Time Frame: At memory testing 1 day later ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 39 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02515890


Locations
Layout table for location information
United States, Pennsylvania
University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213
Sponsors and Collaborators
University of Pittsburgh
Investigators
Layout table for investigator information
Principal Investigator: Keith M Vogt, MD, PhD University of Pittsburgh

Layout table for additonal information
Responsible Party: Keith M. Vogt, MD, PhD, Assistant Professor, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT02515890     History of Changes
Other Study ID Numbers: PRO14050609
First Posted: August 5, 2015    Key Record Dates
Last Update Posted: December 17, 2018
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Data will be published. After all analysis and dissemination is complete, functional images will be shared via data repository.
Keywords provided by Keith M. Vogt, MD, PhD, University of Pittsburgh:
midazolam
dexmedetomidine
memory
ketamine
Additional relevant MeSH terms:
Layout table for MeSH terms
Amnesia
Memory Disorders
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Neurocognitive Disorders
Mental Disorders
Midazolam
Dexmedetomidine
Ketamine
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Adrenergic alpha-2 Receptor Agonists
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Anesthetics, Dissociative
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents