Sevoflurane's Effect on Neurocognition Study (SENS)
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| ClinicalTrials.gov Identifier: NCT06044740 |
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Recruitment Status :
Recruiting
First Posted : September 21, 2023
Last Update Posted : February 5, 2024
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Anesthesia Pain Amnesia | Drug: Sevoflurane Device: Peripheral Nerve Stimulation | Phase 1 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 60 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Basic Science |
| Official Title: | Sevoflurane's Effect on Neurocognition Study |
| Actual Study Start Date : | January 17, 2024 |
| Estimated Primary Completion Date : | July 1, 2025 |
| Estimated Study Completion Date : | July 1, 2025 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Sevoflurane+Pain
Single-arm study. All subjects receive sevoflurane and painful electric nerve stimulation, as described in the interventions.
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Drug: Sevoflurane
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).
Other Name: Ultane Device: Peripheral Nerve Stimulation 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.
Other Name: Electric Nerve Stimulation |
- functional magnetic resonance imaging activation in response to experimental tasks [ Time Frame: Visit 1: Immediate; average activity, calculated from each task scan ]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 [ Time Frame: Visit 1: Immediate; brain activity captured in data acquired across entire 6-8 minute scan. ]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.
- Explicit memory performance [ Time Frame: Visit 2: 24-hrs post-learning experiment ]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.
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| Ages Eligible for Study: | 18 Years to 59 Years (Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | Yes |
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)
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): NCT06044740
| Contact: Keith M Vogt, MD, PhD | 4126473147 | kev18@pitt.edu |
| United States, Pennsylvania | |
| University of Pittsburgh | Recruiting |
| Pittsburgh, Pennsylvania, United States, 15213 | |
| Contact: Keith M Vogt, MD, PhD kev18@pitt.edu | |
| Principal Investigator: | Keith M Vogt, MD, PhD | University of Pittsburgh |
| Responsible Party: | Keith M. Vogt, MD, PhD, Associate Professor, University of Pittsburgh |
| ClinicalTrials.gov Identifier: | NCT06044740 |
| Other Study ID Numbers: |
STUDY23070068 R35GM146822 ( U.S. NIH Grant/Contract ) |
| First Posted: | September 21, 2023 Key Record Dates |
| Last Update Posted: | February 5, 2024 |
| Last Verified: | February 2024 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | De-identified data to share:
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| Supporting Materials: |
Study Protocol |
| 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. |
| Access Criteria: | Data will be shared via a publicly-accessible online platform that allows user download at no cost. |
| 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 |
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functional MRI sevoflurane electric nerve stimulation sedation functional connectivity |
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Amnesia Memory Disorders Neurobehavioral Manifestations Neurologic Manifestations Nervous System Diseases Neurocognitive Disorders Mental Disorders |
Sevoflurane Platelet Aggregation Inhibitors Anesthetics, Inhalation Anesthetics, General Anesthetics Central Nervous System Depressants Physiological Effects of Drugs |