AnesthesiaEarly Phase 1NONINCT06702631

Nitrous Oxide Neuroimaging

A Early Phase 1 study testing Nitrous oxide and Peripheral Nerve Stimulation in people with Anesthesia and Pain, run by Keith M Vogt at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 to 59 yearsHealthy volunteers can take part
Conditions the study is for: Anesthesia, Pain, Amnesia
What is being tested?: Nitrous oxide and Peripheral Nerve Stimulation
Type of treatment: Medical device
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 34 participants
Where: 1 siteUnited States
Study dates: 13 Jan 2025to 30 Jun 2026
Phase: Early Phase 1
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 59 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

have none of the specific exclusion criteria
have a valid email address and valid phone number throughout the study
free from any non-MRI compatible implants

Who cannot join

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)

Show all 18Show fewer

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

Trial locations and contacts

1 site in 1 country.

United States1 site

University of Pittsburgh
Pittsburgh, Pennsylvania, 15213

Other trials in United States

About this study

Official title: Functional MRI of Nitrous Oxide Inhalation in Volunteer Subjects

Read the detailed description

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: Anesthesia, Pain, Amnesia
Being tested: Nitrous oxide, Peripheral Nerve Stimulation
Medical subject headings: Pain, Amnesia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Nitrous oxideDrug
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 StimulationDevice
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.

Study groups in NCT06702631
Study group	Role	What they receive
Nitrous Oxide + Pain	Experimental	Single-arm study. All subjects receive nitrous oxide and painful electric nerve stimulation, as described in the interventions. Receives: Drug: Nitrous oxide; Device: Peripheral Nerve Stimulation

What is being measured

The primary outcome is the main question the study is designed to answer.

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

Secondary outcomes (1)

Explicit memory performance
Recognition memory testing, using the Remember-Know procedure, in which subjects indicate whether they recognize previously experienced experimental items among novel items (not previously in the experiment). This allows calculation of interdependent measures of recollection \& familiarity using the signal detection statistic, d'. d' is calculated as the cumulative Gaussian distribution of false positive responses subtracted from the cumulative Gaussian distribution of correctly identified previously-experienced items. d' is on a (theoretically infinite) scale of standard deviation units, with negative values representing performance worse than chance guessing and positive values representing stand deviations of performance above chance.
Measured: Visit 2: 24 hours post-learning experiment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

13 Jan 202530 Jun 2026

First posted25 Nov 2024
Study start13 Jan 2025
Primary completion30 Jun 2026
Study completion30 Jun 2026

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for AnesthesiaStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Early Phase 1
Primary purpose: Basic science
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 34 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT06702631
Sponsor's protocol ID: STUDY24100059
Other IDs: R35GM146822
Acronym: NONI
Status last verified: Aug 2026
First submitted: 20 Nov 2024
Last updated: 19 Aug 2026
Results posted: No
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: Yes
Individual data sharing: Yes: De-identified data to share: * age, height, weight, sex * survey instruments to quantify pain predispositions (catastrophizing, vigilance \& anxiety), depression, anxiety, stress, and sleep * pain intensity \& unpleasantness, and observer assessment of sedation at the targeted drug dose * Behavioral performance data for long-term memory * structural and functional magnetic resonance images

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 19 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Functional MRI of Nitrous Oxide Inhalation in Volunteer Subjects
ClinicalTrials.gov ID: NCT06702631
Acronym / sponsor ID: NONI / STUDY24100059
Conditions: Anesthesia, Pain, Amnesia
Phase: Early Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 34 participants (actual)
Lead sponsor: Keith M VogtUniversity, hospital or other
Collaborators: National Institute of General Medical Sciences (NIGMS)
Study start: 13 Jan 2025 (actual)
Primary completion: 30 Jun 2026 (actual)
Study completion: 30 Jun 2026 (actual)
First posted: 25 Nov 2024 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

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:

Study design

Primary purpose: Basic science
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Nitrous Oxide + Pain	Experimental	Drug: Nitrous oxide, Device: Peripheral Nerve StimulationSingle-arm study. All subjects receive nitrous oxide and painful electric nerve stimulation, as described in the interventions.

Who may qualify

Ages: 18 to 59 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (3 listed)

have none of the specific exclusion criteria
have a valid email address and valid phone number throughout the study
free from any non-MRI compatible implants

Key exclusion criteria (18 listed)

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)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Nitrous oxideAfter 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).	Drug	Nitrous Oxide + Pain
Peripheral Nerve StimulationExperimental 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.	Device	Nitrous Oxide + Pain

Primary outcome

Brain activation to painful stimulation difference: Drug-free condition minus nitrous oxide condition
Time frame: Visit 1: Immediate; average activity, calculated from each task scan
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.
Resting-state functional connectivity difference: Drug-free minus nitrous oxide condition
Time frame: Visit 1: Immediate; brain activity captured in data acquired across entire 6-8 minute scan.
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.

1 secondary outcome

Explicit memory performance
Time frame: Visit 2: 24 hours post-learning experiment

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 19 Aug 2026.
Individual participant dataSharing planned: Yes. De-identified data to share: * age, height, weight, sex * survey instruments to quantify pain predispositions (catastrophizing, vigilance \& anxiety), depression, anxiety, stress, and sleep * pain intensity \& unpleasantness, and observer assessment of sedation at the targeted drug dose * Behavioral performance data for long-term memory * structural and functional magnetic resonance images

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing Nitrous oxide and Peripheral Nerve Stimulation in people with Anesthesia and Pain, run by Keith M Vogt at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Brain activation to painful stimulation difference: Drug-free condition minus nitrous oxide condition (time frame: Visit 1: Immediate; average activity, calculated from each task scan). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06702631.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Aug 2026.