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Sevoflurane's Effect on Neurocognition Study (SENS)

Primary Purpose

Anesthesia, Pain, Amnesia

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Sevoflurane
Peripheral Nerve Stimulation
Sponsored by
Keith M. Vogt, MD, PhD
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Anesthesia focused on measuring functional MRI, sevoflurane, electric nerve stimulation, sedation, functional connectivity

Eligibility Criteria

18 Years - 59 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria: Adults, age 18-59, 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 Exclusion Criteria: being pregnant or attempting to conceive having a body mass index (BMI) > 35 having significant memory impairment or hearing loss having sleep apnea having chronic pain or frequently taking pain medication (including tramadol) having any severe or poorly-controlled medical problem (hypertension, diabetes) having neurologic or psychiatric disease, including anxiety, and depression having significant cardiac valvular disease or cardiomyopathy having a history of abnormal heartbeats (cardiac conduction abnormality or arrhythmia) having a history of seizures or convulsions having a history of liver disease having a history of asthma or other significant pulmonary disease having a history of malignant hyperthermia, muscular dystrophy, central core disease, or hyperkalemia being claustrophobic have metal implants or non-removable metal piercings having a history of adverse reaction to anesthetics daily alcohol or heavy alcohol use; history of alcohol abuse current daily smoker regular or recent marijuana use (including prescribed/medical marijuana) illicit drug use regularly taking: antiepileptics, antidepressants, anti-psychotics, antihistamines, anti-anxiety medication, stimulants, or sleep-aids current use of selective serotonin reuptake inhibitors (SSRIs), noradrenaline reuptake inhibitors (SNRIs), or monoamine oxidase inhibitors (MAOIs) and some other specific drugs phenytoin, carbamazepine, and rifampin history of QT prolongation hypersensitivity or allergic reaction to ondansetron (Zofran)

Sites / Locations

  • University of PittsburghRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Sevoflurane+Pain

Arm Description

Single-arm study. All subjects receive sevoflurane and painful electric nerve stimulation, as described in the interventions.

Outcomes

Primary Outcome Measures

functional magnetic resonance imaging activation in response to experimental tasks
Event-related blood-oxygen level dependent (BOLD) Magnetic Resonance Imaging (MRI) responses will be determined for each experimental item presented, revealing localized changes in blood flow, which correlate to increased neuronal activity. These will be averaged across the multiple repetitions of each type of experimental item (memory only, pain only, and memory+pain), creating an anatomical map of Z-scores. Cross-condition comparisons will be the main effect of interest, comparing saline to low concentration sevoflurane AND comparing saline to high concentration sevoflurane.
Functional connectivity
Whole-brain functional connectivity will be determined in each condition (no-sevoflurane, low-dose, and high-dose). This generates a matrix of cross-correlation values. Cross-condition comparisons will be the main effect of interest, comparing no sevoflurane to low concentration sevoflurane AND comparing no-sevoflurane to high concentration sevoflurane.

Secondary Outcome Measures

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.

Full Information

First Posted
September 1, 2023
Last Updated
September 17, 2023
Sponsor
Keith M. Vogt, MD, PhD
Collaborators
National Institute of General Medical Sciences (NIGMS)
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1. Study Identification

Unique Protocol Identification Number
NCT06044740
Brief Title
Sevoflurane's Effect on Neurocognition Study
Acronym
SENS
Official Title
Sevoflurane's Effect on Neurocognition Study
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 1, 2023 (Anticipated)
Primary Completion Date
July 1, 2025 (Anticipated)
Study Completion Date
July 1, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Keith M. Vogt, MD, PhD
Collaborators
National Institute of General Medical Sciences (NIGMS)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
Yes
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this study is to determine the effects of acute pain on long-term memory and conditioned physiologic responses in the presence and absence of low dose sevoflurane. Functional magnetic resonance imaging will be used to identify the neural correlates of these phenomena. The study will occur over 2 visits and involves no long-term follow up.
Detailed Description
This is a non-randomized, clinical trial study of healthy volunteer subjects, which will employ neuroimaging and behavioral measures to characterize the effects of inhalational sevoflurane on pain processing and cognitive function. Sedative doses of sevoflurane will be targeted, and steady-state end-tidal (expired) concentrations achieved, while subjects perform a pain and memory cognitive task. At both no-drug baseline and the targeted doses, task and resting-state functional magnetic resonance imaging (MRI) scans will be acquired, and this data will be analyzed subsequently for task-related brain activity(from pain processing and memory formation) and functional connectivity. This work will use a systems neuroscience approach to fill an important knowledge gap about the central effects of inhalational sevoflurane in the context of painful stimulation. The investigators propose to complete the following 3 Aims, at 2 targeted sedative doses of Sevoflurane, compared to no-drug baseline, using functional MRI: Aim 1: Determine how the brain response to acute pain stimulation is modulated by sevoflurane. It is anticipated that sevoflurane will correlate to decreased activation in both somatosensory (thalamus, insula, primary somatosensory/motor) and affective (anterior cingulate) components of the pain processing brain areas. Aim 2: Determine how memory encoding is modulated by sevoflurane, in the context of periodic painful stimulation. It is anticipated that sevoflurane will correlate to decreased activation in both the explicit memory (hippocampus, parahippocampus) and associative learning (amygdala, anterior cingulate) brain systems. Aim 3: Determine the neural effects of inhalational sevoflurane on brain connectivity both at rest and during the combined pain and memory task performance. It is anticipated that hypothesize that sevoflurane will cause widespread dose-dependent decreases in long-range functional connectivity between brain areas known to be involved in pain processing and to the default mode network, and that this connectivity will differ between the resting (task-free) and periodic pain states.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Anesthesia, Pain, Amnesia
Keywords
functional MRI, sevoflurane, electric nerve stimulation, sedation, functional connectivity

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Sevoflurane+Pain
Arm Type
Experimental
Arm Description
Single-arm study. All subjects receive sevoflurane and painful electric nerve stimulation, as described in the interventions.
Intervention Type
Drug
Intervention Name(s)
Sevoflurane
Other Intervention Name(s)
Ultane
Intervention Description
After a no-drug control period, subjects will inhale sevoflurane, administered via a breathing circuit and face mask, until a steady-state target end-tidal expired concentration is reached. During the two drug conditions, subjects will first receive low-dose sevoflurane (0.4% corresponding to 0.2 Minimum Alveolar Concentration) and then a higher dose sevoflurane condition (0.8% corresponding to 0.4 Minimum Alveolar Concentration).
Intervention Type
Device
Intervention Name(s)
Peripheral Nerve Stimulation
Other Intervention Name(s)
Electric Nerve Stimulation
Intervention Description
Experimental acute pain stimulus will be delivered using a nerve stimulator. These painful shocks will be paired with a fixed number of the experimental cues, in a pattern that appears random to participants.
Primary Outcome Measure Information:
Title
functional magnetic resonance imaging activation in response to experimental tasks
Description
Event-related blood-oxygen level dependent (BOLD) Magnetic Resonance Imaging (MRI) responses will be determined for each experimental item presented, revealing localized changes in blood flow, which correlate to increased neuronal activity. These will be averaged across the multiple repetitions of each type of experimental item (memory only, pain only, and memory+pain), creating an anatomical map of Z-scores. Cross-condition comparisons will be the main effect of interest, comparing saline to low concentration sevoflurane AND comparing saline to high concentration sevoflurane.
Time Frame
Visit 1: Immediate; average activity, calculated from each task scan
Title
Functional connectivity
Description
Whole-brain functional connectivity will be determined in each condition (no-sevoflurane, low-dose, and high-dose). This generates a matrix of cross-correlation values. Cross-condition comparisons will be the main effect of interest, comparing no sevoflurane to low concentration sevoflurane AND comparing no-sevoflurane to high concentration sevoflurane.
Time Frame
Visit 1: Immediate; brain activity captured in data acquired across entire 6-8 minute scan.
Secondary Outcome Measure Information:
Title
Explicit memory performance
Description
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.
Time Frame
Visit 2: 24-hrs post-learning experiment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
59 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Adults, age 18-59, 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 Exclusion Criteria: being pregnant or attempting to conceive having a body mass index (BMI) > 35 having significant memory impairment or hearing loss having sleep apnea having chronic pain or frequently taking pain medication (including tramadol) having any severe or poorly-controlled medical problem (hypertension, diabetes) having neurologic or psychiatric disease, including anxiety, and depression having significant cardiac valvular disease or cardiomyopathy having a history of abnormal heartbeats (cardiac conduction abnormality or arrhythmia) having a history of seizures or convulsions having a history of liver disease having a history of asthma or other significant pulmonary disease having a history of malignant hyperthermia, muscular dystrophy, central core disease, or hyperkalemia being claustrophobic have metal implants or non-removable metal piercings having a history of adverse reaction to anesthetics daily alcohol or heavy alcohol use; history of alcohol abuse current daily smoker regular or recent marijuana use (including prescribed/medical marijuana) illicit drug use regularly taking: antiepileptics, antidepressants, anti-psychotics, antihistamines, anti-anxiety medication, stimulants, or sleep-aids current use of selective serotonin reuptake inhibitors (SSRIs), noradrenaline reuptake inhibitors (SNRIs), or monoamine oxidase inhibitors (MAOIs) and some other specific drugs phenytoin, carbamazepine, and rifampin history of QT prolongation hypersensitivity or allergic reaction to ondansetron (Zofran)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Keith M Vogt, MD, PhD
Phone
4126473147
Email
kev18@pitt.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Keith M Vogt, MD, PhD
Organizational Affiliation
University of Pittsburgh
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Pittsburgh
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Keith M Vogt, MD, PhD
Email
kev18@pitt.edu

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
De-identified data to share: age, height, weight, sex survey instruments to quantify pain predispositions (catastrophizing, vigilance & anxiety), depression, anxiety, stress, and sleep pain intensity & unpleasantness, and observer assessment of sedation at the targeted drug dose Behavioral performance data for long-term memory structural and functional MRI images
IPD Sharing Time Frame
After analysis is complete and results have been published, all the above data will be shared in de-identified format, linked together by an assigned subject number.
IPD Sharing Access Criteria
Data will be shared via a publicly-accessible online platform that allows user download at no cost.

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Sevoflurane's Effect on Neurocognition Study

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