Nitrous Oxide Neuroimaging

NCT ID: NCT06702631

Last Updated: 2025-12-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

EARLY_PHASE1

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-01-13

Study Completion Date

2026-06-01

Brief Summary

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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.

Detailed Description

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This is a non-randomized, clinical trial study of healthy volunteer subjects, which will employ neuroimaging and behavioral measures to characterize the effects of inhalational nitrous oxide on pain processing and cognitive function. Sedative doses of nitrous oxide will be targeted, and steady-state end-tidal (expired) concentrations achieved, while subjects perform a pain and memory cognitive task. At both no-drug baseline and the targeted doses, task and resting-state functional magnetic resonance imaging (MRI) scans will be acquired, and this data will be analyzed subsequently for task-related brain activity (from pain processing and memory formation) and functional connectivity. This work will use a systems neuroscience approach to fill an important knowledge gap about the central effects of inhalational nitrous oxide in the context of painful stimulation.

The investigators propose to complete the following 3 Aims, at a targeted sedative dose of nitrous oxide, compared to no-drug baseline, using functional MRI:

Aim 1: Determine how the brain response to acute pain stimulation is modulated by nitrous oxide. It is anticipated that nitrous oxide will correlate to decreased activation in both somatosensory (thalamus, insula, primary somatosensory/motor) and affective (anterior cingulate) components of the pain processing brain areas.

Aim 2: Determine how memory encoding is modulated by nitrous oxide, in the context of periodic painful stimulation. It is anticipated that nitrous oxide will correlate to decreased activation in both the explicit memory (hippocampus, parahippocampus) and associative learning (amygdala, anterior cingulate) brain systems.

Aim 3: Determine the neural effects of inhalational nitrous oxide on brain connectivity both at rest and during the combined pain and memory task performance. It is anticipated that nitrous oxide will cause widespread dose-dependent decreases in long-range functional connectivity between brain areas known to be involved in pain processing and to the default mode network, and that this connectivity will differ between the resting (task-free) and periodic pain states.

Conditions

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Anesthesia Pain Amnesia

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

Study Groups

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Nitrous Oxide + Pain

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

Group Type EXPERIMENTAL

Nitrous oxide

Intervention Type 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).

Peripheral Nerve Stimulation

Intervention Type 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.

Interventions

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Nitrous oxide

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).

Intervention Type DRUG

Peripheral Nerve Stimulation

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.

Intervention Type DEVICE

Eligibility Criteria

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Exclusion Criteria

* 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
* daily alcohol or heavy alcohol use; history of alcohol abuse
* current daily smoker
* regular or recent marijuana use (including prescribed/medical marijuana)
* illicit drug use, i.e., street drugs
* regularly taking: antiepileptics, antidepressants, anti-psychotics, antihistamines, anti-anxiety medication, stimulants, or sleep-aids
Minimum Eligible Age

18 Years

Maximum Eligible Age

59 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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National Institute of General Medical Sciences (NIGMS)

NIH

Sponsor Role collaborator

Keith M Vogt

OTHER

Sponsor Role lead

Responsible Party

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Keith M Vogt

Associate Professor

Responsibility Role SPONSOR_INVESTIGATOR

Locations

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University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Keith M Vogt, MD, PhD

Role: CONTACT

Phone: 4126473147

Email: [email protected]

Other Identifiers

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R35GM146822

Identifier Type: NIH

Identifier Source: secondary_id

View Link

STUDY24100059

Identifier Type: -

Identifier Source: org_study_id