Network-Level Effects of Nitrous Oxide in the Human Brain

Phase 4

Completed

• Conditions: Healthy
• Interventions: Drug: Nitrous Oxide Gas for Inhalation

• Registration Number: NCT03435055
• Lead Sponsor: University of Michigan

Brief Summary

The purpose of this study is to understand how a commonly used drug, nitrous oxide, acts on the brain to reduce pain. Nitrous oxide is commonly used in anesthesiology but there is limited knowledge on how this drug affects functional networks in the brain.

Detailed Description

The objective of this study is to identify the network transformations that account for the analgesic effects of nitrous oxide. Our hypothesis is that analgesic doses of nitrous oxide increase network efficiency and disrupt normal pain processingOur approach is to administer subanesthetic nitrous oxide during the acquisition of fMRI (functional magnetic resonance imaging) and EEG (electroencephalogram).

Study Timeline

• Study Start: 2017-07-21
• Study First Submitted: 2018-01-25
• Study First Submitted QC: 2018-02-14
• Study First Posted: 2018-02-15
• Primary Completion: 2019-10-11
• Study Completion: 2019-10-11
• Disposition First Submitted: 2020-09-21
• Results First Submitted: 2021-04-30
• Results First Submitted QC: 2021-06-17
• Disposition First Submitted QC: 2021-06-17
• Results First Posted: 2021-07-09
• Disposition First Posted: 2021-07-09
• Status Verified: 2021-11
• Last Update Submitted: 2021-11-02
• Last Update Posted: 2021-11-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 21

Inclusion Criteria

1. Body mass index <30
2. Must be right-handed
3. Must be capable of giving written informed consent

Read More

Exclusion Criteria

1. History of obstructive sleep apnea;
2. History of a difficult airway with a previous anesthetic
3. Gastroesophageal reflux;
4. Hypertension or other cardiovascular abnormalities;
5. Pulmonary hypertension;
6. History of recreational drug use;
7. History of chronic alcohol abuse
8. Having any chronic medical illness involving pain;
9. History of major depression;
10. History of psychosis or bipolar disorder;
11. History of methylenetetrahydrofolate reductase deficiency;
12. History of a known hypersensitivity to ketamine, midazolam, Zofran, labetalol or glycopyrrolate
13. History of seizures or other neurologic disorders;
14. Pregnant or nursing mothers;
15. Tattoos on the head or neck region - all other tattoos are subject to determination by investigators;
16. Contraindications to neuroimaging methods;
17. Any impairment, activity or situation that in the judgment of the Study Coordinator or Principal Investigators would prevent satisfactory completion of the study protocol.

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Nitrous Oxide - inhaled	Nitrous Oxide Gas for Inhalation	Each volunteer will participate in one scanning visit in which simultaneous functional magnetic resonance imaging (fMRI) and electroencephalogram (EEG) data will be collected wherein they receive placebo (20 minutes) followed by inhaled nitrous oxide at subanalgesic levels (35% inhaled concentration) over 40 minutes.

Primary Outcome Measures

Name	Time	Method
Functional Connectivity Associated With Tonic Stimulus	Baseline to 50 minutes	Functional connectivity measures will be assessed at rest (baseline) and during a tonic cuff stimulus (6-minutes). Seed-to-whole brain functional connectivity (Fisher's r-transformed z) will be measured from the left anterior insula, previously shown to be involved in pain and sensory processing. Paired t-test were conducted on subject specific beta maps to identify changes in connectivity associated with nitrous oxide in SPM12. The z-score descriptors represent the Fishers-r-to-z transformed. Here the z-score is a transformation of the Pearson's (r) correlation coefficient of the BOLD timeseries between two brain regions. Higher z-scores are associated with higher correlations in timeseries and correspond with higher functional connectivity between two brain regions.
Functional Connectivity During Nitrous Oxide	Baseline to 50 minutes	Functional connectivity measures will be assessed at rest (baseline) and during sub anesthetic dose nitrous oxide (nitrous oxide). Seed-to-whole brain functional connectivity (Fisher's r-transformed z) will be measured from the left anterior insula, previously shown to be involved in pain and sensory processing. Paired t-test were conducted on subject specific beta maps to identify changes in connectivity associated with nitrous oxide in SPM12. The z-score descriptors represent the Fishers-r-to-z transformed. Here the z-score is a transformation of the Pearson's (r) correlation coefficient of the BOLD timeseries between two brain regions. Higher z-scores are associated with higher correlations in timeseries and correspond with higher functional connectivity between two brain regions.

Secondary Outcome Measures

Name	Time	Method
Tonic Stimulus Intensity During Nitrous Oxide	Baseline to 50 minutes	Participants will receive a tonic (6 minutes) pressure applied to the lower leg at baseline and under subanesthetic dose of nitrous oxide (35% inhaled concentration). Following each pressure stimulus, participants will rate the pain intensity of the tonic stimulus (0 ="no pain", 10= "worst pain imaginable", Visual Analog Scale, e.g pain intensity).
Spectral Power of Sub-anesthetic Dose of Nitrous Oxide	Baseline to 50 minutes	Brain imaging data were obtained from functional magnetic resonance imaging (fMRI) data recorded simultaneously with electroencephalography (EEG) data at baseline and under a sub-anesthetic dose of nitrous oxide. Spectral data were averaged from EEG data at all electrodes collected during the baseline and sub-anesthetic dose (35%) of nitrous oxide to observe changes in spectral power. The EEG power spectrum was divided into three frequency bands: Delta = 1-3 Hz; Theta = 4-7 Hz; and Alpha = 8 - 13 Hz

Trial Locations

Locations (1)

Michigan Medicine - University of Michigan; 🇺🇸 Ann Arbor, Michigan, United States