Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Memory Modulation by Pain During Anesthesia (MMA)

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 : Completed
First Posted : August 5, 2015
Results First Posted : July 1, 2020
Last Update Posted : July 1, 2020
Sponsor:
Collaborator:
Foundation for Anesthesia Education and Research
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 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.

Condition or disease Intervention/treatment Phase
Amnesia Pain Anesthesia Drug: Dexmedetomidine Drug: Midazolam Device: Peripheral nerve stimulation Drug: Ketamine Phase 1

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 32 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention 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 (Participant)
Primary Purpose: Basic Science
Official Title: Modulation of Long-term Memory by the Experience of Pain During Sedation With Anesthetics
Actual Study Start Date : November 19, 2015
Actual Primary Completion Date : December 12, 2018
Actual Study Completion Date : December 12, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Memory

Arm Intervention/treatment
Experimental: Dexmedetomidine Only
All subjects receive saline (control), followed by a dexmedetomidine infusion. They also experience intermittent experimental pain delivered by peripheral nerve stimulation.
Drug: Dexmedetomidine
Selected subjects received this drug during a portion of the study
Other Name: Precedex

Device: Peripheral 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.
Other Name: electric nerve stimulation

Experimental: Midazolam Only
Subjects receive saline (control), followed by midazolam infusion. They also experience intermittent experimental pain delivered by peripheral nerve stimulation.
Drug: Midazolam
Selected subjects received this drug during a portion of the study
Other Name: Versed

Device: Peripheral 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.
Other Name: electric nerve stimulation

Experimental: Ketamine Only
All subjects receive saline (control), followed by ketamine infusion. They also experience intermittent experimental pain delivered by peripheral nerve stimulation.
Device: Peripheral 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.
Other Name: electric nerve stimulation

Drug: Ketamine
Selected subjects received this drug during a portion of the study
Other Name: Ketalar

Experimental: 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.

Drug: Midazolam
Selected subjects received this drug during a portion of the study
Other Name: Versed

Device: Peripheral 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.
Other Name: electric nerve stimulation

Drug: Ketamine
Selected subjects received this drug during a portion of the study
Other Name: Ketalar

Experimental: 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.

Drug: Midazolam
Selected subjects received this drug during a portion of the study
Other Name: Versed

Device: Peripheral 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.
Other Name: electric nerve stimulation

Drug: Ketamine
Selected subjects received this drug during a portion of the study
Other Name: Ketalar




Primary Outcome Measures :
  1. 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.



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
Foundation for Anesthesia Education and Research
Investigators
Layout table for investigator information
Principal Investigator: Keith M Vogt, MD, PhD University of Pittsburgh
  Study Documents (Full-Text)

Documents provided by Keith M. Vogt, MD, PhD, University of Pittsburgh:
Statistical Analysis Plan  [PDF] April 24, 2020
Informed Consent Form  [PDF] February 23, 2018
Study Protocol  [PDF] January 30, 2019

Layout table for additonal information
Responsible Party: Keith M. Vogt, MD, PhD, Assistant Professor, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT02515890    
Other Study ID Numbers: PRO14050609
First Posted: August 5, 2015    Key Record Dates
Results First Posted: July 1, 2020
Last Update Posted: July 1, 2020
Last Verified: June 2020
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.

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: Yes
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
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
Adjuvants, Anesthesia