An Early Phase 1 interventional study of Nitrous oxide and Peripheral Nerve Stimulation in Anesthesia, Pain and Amnesia, sponsored by Keith M Vogt. Completed at 1 site in United States. Open to participants aged 18 Years to 59 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-08-19.
Sponsored by Keith M Vogt · Early Phase 1, Interventional, and Basic science
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.
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.
10,054 studies on the registry are indexed under Pain; 1,649 are open to participants now.
This study's enrollment of 34 is below the median of 66 across 8,493 interventional studies indexed under Pain.
Browse Pain studies →Keith M Vogt is the lead sponsor of 7 studies on the registry; 3 are open to participants now.
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Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
BMI (body mass index)
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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
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).
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.
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.
Time frame: 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.
Time frame: Visit 1: Immediate; brain activity captured in data acquired across entire 6-8 minute scan.
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.
Time frame: Visit 2: 24 hours post-learning experiment
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: 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
Supporting information: 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.
This study is completed, as verified in Aug 2026. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Nitrous Oxide
Keith M Vogt