A Test of Neural Inertia in Humans With Xenon

The dual objectives of this study are to determine if the phenomenon of neural inertia is present in humans and to determine whether the order of neurocognitive function is invariant among anesthetic agents. This study will enroll 24 healthy volunteers, ages 20-40 years, who will receive xenon gas (concentrations ranging from 0% to 60%) delivered via inhaled route through the ENHANCER 3000.

Study Overview

• Status: Completed
• Conditions: Neurocognitive Dysfunction
• Intervention / Treatment: Drug: Xenon

Detailed Description

This is a multimodal, nonrandomized study of healthy subjects. After meeting enrollment criteria, subjects will receive a baseline neurocognitive testing on a computer for 15 minutes and will then receive a wrist watch actigraphy device to record their rest/activity patterns over 8-14 days. On the study day (roughly two weeks later), repeat baseline neurocognitive testing will be performed after subjects are fitted with a high density EEG head cap. The actual intervention (delivery of inhaled xenon gas in stepwise increasing followed by decreasing doses) should occur over 2 hours along with verbal tests to assess the presence/absence of consciousness at each xenon concentration. Xenon doses have been chosen specifically to evaluate the point at which individuals lose and then regain consciousness. Doses are escalated up through those used in human anesthesiology (75%) that permit surgery. After exposure, serial neurocognitive testing will occur every 30 minutes for 3 hours post emergence. Subjects are discharged from the study's intervention day to home only upon reaching standard post-anesthesia care unit criteria (modified Aldrete score ≥9). A post-procedure follow up phone call will occur within 24 hours of anesthetic exposure to ensure that the subject remains well. The individual's involvement is completed upon returning the Actigraphy watch 1 week after the exposure day. The expected duration of subject participation is 3 weeks.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania, Perelman School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy volunteers ages 20-40 years old
• American Society of Anesthesiologists (ASA) Physical Status I or II (i.e. healthy)
• Body Mass Index <30 kg/m2
• Easily visible uvula

Exclusion Criteria:

• Any physical signs that would suggest a difficult airway (e.g. mouth opening <3cm, short distance between the chin and neck, poor mandibular subluxation, thick neck)
• History of reactive airway disease
• Current or history of neuropsychiatric disorders
• History or current use of psychotropic medications,
• History or current obstructive sleep apnea
• Current or history of cardiovascular disease or arrhythmias,
• Current or history of chronic sleep disorders
• History of postoperative nausea/vomiting
• Family history of problems with anesthesia (including but not limited to malignant hyperthermia),
• Current or history of Motion sickness
• Current tobacco use
• Current pregnancy or currently breastfeeding
• Positive urine toxicology screen
• History of seizure disorder, head injury, or brain tumor
• Alcohol consumption greater than 12 drinks per week or more than 4 drinks on any single day
• Inability to provide informed consent
• Inability to achieve mask seal on intervention day

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Xenon; Xenon anesthesia to determine if neural inertia is present in humans as visualized by CT imaging.	Drug: Xenon; drug given in concentrations of 0% to 60% over period of 2 hours

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
xenon concentrations at which consciousness is lost and regained	To determine in healthy human volunteers if the brain concentrations of xenon (as determined by CT imaging) are identical at the point of loss and return of consciousness.	4 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neurocognitive recovery upon emergence from xenon as measured by neurocognitive battery testing	To determine if the order of neurocognitive recovery upon emergence from xenon general anesthesia is sequential or simultaneous and if the former is true to determine if the pattern is identical to that of isoflurane (as measured in a previously completed study).	4 hours
Effects of xenon on gross motor activity as measured by actigraphy	To determine if xenon induces transient phase shifts in rest-activity rhythms (as measured from actigraphy) as has been previously reported for isoflurane.	3 weeks
Effects of xenon on brain electrical activity as measured by EEG	To determine effects of xenon on brain electrical activity corresponding to loss and subsequent return of consciousness and also at points corresponding to return as each neurocognitive domain returns to its baseline following exposure to xenon as measured by electroencephalogram (EEG).	4 hours

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Investigators: Principal Investigator: Maz B Kelz, MD, PhD, University of Pennsylvania

Study record dates

Study Major Dates

• Study Start: April 1, 2016
• Primary Completion (Actual): December 1, 2019
• Study Completion (Actual): December 1, 2021

Study Registration Dates

• First Submitted: April 15, 2016
• First Submitted That Met QC Criteria: May 10, 2016
• First Posted (Estimate): May 11, 2016

Study Record Updates

• Last Update Posted (Actual): July 8, 2022
• Last Update Submitted That Met QC Criteria: July 6, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: neurocognitive function; neural inertia; xenon gas
• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Cognitive Dysfunction; Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics, General; Anesthetics; Anesthetics, Inhalation; Xenon
• Other Study ID Numbers: 824229

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No