Nitrous Oxide Neuroimaging

NCT06702631 | Recruiting Early Phase 1 FDA Drug FDA Device

• 2 other identifiers: STUDY24100059R35GM146822
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine the effects of acute pain on long-term memory and conditioned physiologic responses in the presence and absence of low dose nitrous oxide. Functional magnetic resonance imaging will be used to identify the neural correlates of these phenomena. The study will occur over 2 visits and involves no long-term follow up.

Conditions

Anesthesia; Pain; Amnesia

Outcome Measures

Primary Outcomes (2)

• Brain activation to painful stimulation difference: Drug-free condition minus nitrous oxide condition

  Event-related blood-oxygen level dependent Magnetic Resonance Imaging (MRI) responses will be determined. Z-scores will be calculated by linear regression of the task timing against the MRI signal time-course (MRI data is in arbitrary units with no maximum or minimum) at each voxel (single data point in brain). Primary outcome will be for the right insula. Z-score of 0 indicates no task-related changes. Z-scores further from zero indicate stronger correlation between functional MRI signal change and the task timing, with positive values indicating increases in functional MRI signal and negative Z-scores indicating decreases. Practically, higher positive Z-scores would indicate increased brain activity and larger negative Z-scores would indicate decreased brain activity.

  Visit 1: Immediate; average activity, calculated from each task scan

• Resting-state functional connectivity difference: Drug-free minus nitrous oxide condition

  Functional connectivity (FC) will be calculated as the correlation between the time-series of MRI signal (MRI data is in arbitrary units with no maximum or minimum) on a pair-wise basis between every atlas-defined region in the brain. Strength of temporal correlation is reflective of brain regions that are working together, and changes in FC reflect differences in brain state, in this case between the drug-free and nitrous oxide conditions. The reported value will be for FC change between insula and anterior cingulate. T-score of 0 would indicate no condition-related changes in connectivity between the two brain regions. T-scores further from zero indicate stronger connectivity change: positive T-score reflects drug-free \> nitrous oxide; negative T-scores indicate nitrous oxide \> drug-free.

  Visit 1: Immediate; brain activity captured in data acquired across entire 6-8 minute scan.

Secondary Outcomes (1)

• Explicit memory performance

  Visit 2: 24 hours post-learning experiment

Study Arms (1)

Nitrous Oxide + Pain

EXPERIMENTAL

Single-arm study. All subjects receive nitrous oxide and painful electric nerve stimulation, as described in the interventions.

Drug: Nitrous oxide; Device: Peripheral Nerve Stimulation

Interventions

Nitrous oxide DRUG

After a no-drug control period, subjects will inhale nitrous oxide, administered via a breathing circuit and face mask, until a steady-state target end-tidal expired concentration is reached. During the drug condition, subjects will receive low-dose nitrous oxide (% corresponding to Minimum Alveolar Concentration).

Nitrous Oxide + Pain

Peripheral Nerve Stimulation DEVICE

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.

Nitrous Oxide + Pain

Eligibility Criteria

• Age: 18 Years - 59 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may not qualify if:

• have a valid email address and valid phone number throughout the study
• free from any non-MRI compatible implants
• are pregnant or attempting to conceive
• body mass index (BMI) \> 35
• significant memory impairment or hearing loss
• sleep apnea
• chronic pain or frequently taking pain medication (including tramadol)
• any severe or poorly-controlled medical problem (hypertension, diabetes)
• neurologic or psychiatric disease, including anxiety, and depression
• severe cardiac disease
• history of methylenetetrahydrofolate reductase (MTHFR) deficiency or variant mutation, as assessed by personal report
• recent ear or eye surgery
• being claustrophobic
• have metal implants or non-removable metal piercings
• having a history of adverse reaction to anesthetics

Sponsors & Collaborators

• Keith M Vogt: lead
• National Institute of General Medical Sciences (NIGMS): collaborator

Study Sites (1)

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

RECRUITING

MeSH Terms

Conditions

Pain; Amnesia

Interventions

Nitrous Oxide

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Memory Disorders; Neurobehavioral Manifestations; Nervous System Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Nitrogen Oxides; Gases; Inorganic Chemicals; Nitrogen Compounds; Oxides; Oxygen Compounds

Central Study Contacts

Keith M Vogt, MD, PhD

CONTACT

4126473147; kev18@pitt.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: November 20, 2024
• First Posted: November 25, 2024
• Study Start: January 13, 2025
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: April 15, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: 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.

Locations

US (1)