Network-Level Effects of Nitrous Oxide in the Human Brain

NCT03435055 | Completed Phase 4 Results FDA Drug

• 1 other identifier: HUM00096321
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy

Outcome Measures

Primary Outcomes (2)

• Functional Connectivity During Nitrous Oxide

  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.

  Baseline to 50 minutes

• Functional Connectivity Associated With Tonic Stimulus

  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.

  Baseline to 50 minutes

Secondary Outcomes (2)

• Tonic Stimulus Intensity During Nitrous Oxide

  Baseline to 50 minutes

• Spectral Power of Sub-anesthetic Dose of Nitrous Oxide

  Baseline to 50 minutes

Study Arms (1)

Nitrous Oxide - inhaled

EXPERIMENTAL

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.

Drug: Nitrous Oxide Gas for Inhalation

Interventions

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.

Nitrous Oxide - inhaled

Eligibility Criteria

• Age: 21 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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;

Sponsors & Collaborators

• University of Michigan: lead

Study Sites (1)

Michigan Medicine - University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Related Publications (1)

• Dai R, Larkin TE, Huang Z, Tarnal V, Picton P, Vlisides PE, Janke E, McKinney A, Hudetz AG, Harris RE, Mashour GA. Classical and non-classical psychedelic drugs induce common network changes in human cortex. Neuroimage. 2023 Jun;273:120097. doi: 10.1016/j.neuroimage.2023.120097. Epub 2023 Apr 7.

  PMID: 37031827 DERIVED

MeSH Terms

Interventions

Endothelium-Dependent Relaxing Factors; Inhalation

Intervention Hierarchy (Ancestors)

Vasodilator Agents; Cardiovascular Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses; Respiratory Mechanics; Respiration; Respiratory Physiological Phenomena; Circulatory and Respiratory Physiological Phenomena

Limitations and Caveats

Data for the Spectral Power of Sub-anesthetic Dose of Nitrous Oxide outcome measure will be analyzed within the coming year and the ClinicalTrials.gov record will be updated at that time.

Results Point of Contact

• Title: Richard Harris
• Organization: University of Michigan

reharris@umich.edu

734-998-6996

Study Officials

• Richard Harris, PhD

  Associate Professor of Anesthesiology and Associate Professor of Internal Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Anesthesiology and Associate Professor of Internal Medicine

Study Record Dates

• First Submitted: January 25, 2018
• First Posted: February 15, 2018
• Study Start: July 21, 2017
• Primary Completion: October 11, 2019
• Study Completion: October 11, 2019
• Last Updated: November 30, 2021
• Results First Posted: July 9, 2021

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)