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Completed

NCT Number: NCT03435055

Network-Level Effects of Nitrous Oxide in the Human Brain

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.

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Key information

Conditions

Healthy

Age range

21 year–40 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Michigan Medicine - University of Michigan

Ann Arbor, Michigan, 48109, United States

About this study

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).

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Body mass index <30
  • Must be right-handed
  • Must be capable of giving written informed consent

Exclusion criteria

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

Treatment and study plan

Nitrous oxide gas for inhalation

Drug

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 subanesthetic levels (35% inhaled concentration) over 40 minutes.

Primary outcomes

  1. Functional Connectivity During Nitrous Oxide

    Time frame: 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.

  2. Functional Connectivity Associated With Tonic Stimulus

    Time frame: 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.

Secondary outcomes

  1. Tonic Stimulus Intensity During Nitrous Oxide

    Time frame: 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).

  2. Spectral Power of Sub-anesthetic Dose of Nitrous Oxide

    Time frame: 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

Sponsors and collaborators

Lead sponsor

University of Michigan

Other

Registry information

Important dates

Study start
2017
Primary completion
2019
Study completion
2019
First posted
Feb 15, 2018
Registry last updated
Nov 30, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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