Trial Outcomes & Findings for Network-Level Effects of Nitrous Oxide in the Human Brain (NCT NCT03435055)
NCT ID: NCT03435055
Last Updated: 2021-11-30
Results Overview
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.
COMPLETED
PHASE4
21 participants
Baseline to 50 minutes
2021-11-30
Participant Flow
A total of 21 participants consented to participate but 2 participants did not participate in any part of the research.
Participant milestones
| Measure |
Nitrous Oxide - Inhaled
Each volunteer will participate in one scanning visit in which simultaneous fMRI/EEG data will be collected wherein they receive placebo (20 minutes) followed by inhaled nitrous oxide at subanalgesic levels (35% inhaled concentration) over 30 minutes.
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|---|---|
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Screening
STARTED
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21
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Screening
COMPLETED
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19
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Screening
NOT COMPLETED
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2
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Received Intervention
STARTED
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19
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Received Intervention
COMPLETED
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16
|
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Received Intervention
NOT COMPLETED
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3
|
Reasons for withdrawal
| Measure |
Nitrous Oxide - Inhaled
Each volunteer will participate in one scanning visit in which simultaneous fMRI/EEG data will be collected wherein they receive placebo (20 minutes) followed by inhaled nitrous oxide at subanalgesic levels (35% inhaled concentration) over 30 minutes.
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|---|---|
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Screening
Physician Decision
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2
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Received Intervention
Did not complete nitrous administration
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3
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Baseline Characteristics
Network-Level Effects of Nitrous Oxide in the Human Brain
Baseline characteristics by cohort
| Measure |
Nitrous Oxide - Inhaled
n=21 Participants
Each volunteer will participate in one scanning visit in which simultaneous fMRI/EEG data will be collected wherein they receive placebo (20 minutes) followed by inhaled nitrous oxide at subanalgesic levels (35% inhaled concentration) over 30 minutes.
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|---|---|
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Age, Continuous
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25 years
n=5 Participants
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Sex: Female, Male
Female
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11 Participants
n=5 Participants
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Sex: Female, Male
Male
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10 Participants
n=5 Participants
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Ethnicity (NIH/OMB)
Hispanic or Latino
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0 Participants
n=5 Participants
|
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Ethnicity (NIH/OMB)
Not Hispanic or Latino
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21 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
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0 Participants
n=5 Participants
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Race (NIH/OMB)
American Indian or Alaska Native
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0 Participants
n=5 Participants
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Race (NIH/OMB)
Asian
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4 Participants
n=5 Participants
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Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
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0 Participants
n=5 Participants
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Race (NIH/OMB)
Black or African American
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2 Participants
n=5 Participants
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|
Race (NIH/OMB)
White
|
14 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
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0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
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PRIMARY outcome
Timeframe: Baseline to 50 minutesPopulation: Three participants had missing data because they did not complete the full scanning protocol.
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.
Outcome measures
| Measure |
Pre-Nitrous
n=16 Participants
Each volunteer will participate in one scanning visit in which simultaneous fMRI/EEG data will be collected as they receive oxygen (20 minutes) followed
Functional connectivity (Fisher's r to z transformed) between the left anterior insula and superior frontal gyrus were measured at baseline.
|
Nitrous Oxide - Subanesthetic Dose
n=16 Participants
Each volunteer will participate in one scanning visit in which simultaneous fMRI/EEG data will be collected as they received subanesthetic dose of nitrous oxide at (35% inhaled concentration) over 30 minutes.
Functional connectivity (z-score) between the left anterior insula and superior frontal gyrus were measured during administration of subanesthetic nitrous oxide.
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Functional Connectivity During Nitrous Oxide
L superior frontal gyrus
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0.1123 Fisher's r transformed z score
Standard Deviation 0.0639
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0.0358 Fisher's r transformed z score
Standard Deviation 0.0620
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Functional Connectivity During Nitrous Oxide
R superior frontal gyrus
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0.1492 Fisher's r transformed z score
Standard Deviation 0.1179
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0.0394 Fisher's r transformed z score
Standard Deviation 0.0950
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PRIMARY outcome
Timeframe: Baseline to 50 minutesPopulation: Number of participants scanned.
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.
Outcome measures
| Measure |
Pre-Nitrous
n=19 Participants
Each volunteer will participate in one scanning visit in which simultaneous fMRI/EEG data will be collected as they receive oxygen (20 minutes) followed
Functional connectivity (Fisher's r to z transformed) between the left anterior insula and superior frontal gyrus were measured at baseline.
|
Nitrous Oxide - Subanesthetic Dose
n=19 Participants
Each volunteer will participate in one scanning visit in which simultaneous fMRI/EEG data will be collected as they received subanesthetic dose of nitrous oxide at (35% inhaled concentration) over 30 minutes.
Functional connectivity (z-score) between the left anterior insula and superior frontal gyrus were measured during administration of subanesthetic nitrous oxide.
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|---|---|---|
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Functional Connectivity Associated With Tonic Stimulus
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-0.0509 Z score
Standard Deviation 0.0822
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0.0486 Z score
Standard Deviation 0.1001
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SECONDARY outcome
Timeframe: Baseline to 50 minutesPopulation: Three participants had missing data because they did not complete the full scanning protocol.
Participants will receive a tonic (6 minutes) pressure applied to the lower leg at baseline and under subanesthetic dose of nitrous oxide (35% inhaled concentration). Following each pressure stimulus, participants will rate the pain intensity of the tonic stimulus (0 ="no pain", 10= "worst pain imaginable", Visual Analog Scale, e.g pain intensity).
Outcome measures
| Measure |
Pre-Nitrous
n=16 Participants
Each volunteer will participate in one scanning visit in which simultaneous fMRI/EEG data will be collected as they receive oxygen (20 minutes) followed
Functional connectivity (Fisher's r to z transformed) between the left anterior insula and superior frontal gyrus were measured at baseline.
|
Nitrous Oxide - Subanesthetic Dose
n=16 Participants
Each volunteer will participate in one scanning visit in which simultaneous fMRI/EEG data will be collected as they received subanesthetic dose of nitrous oxide at (35% inhaled concentration) over 30 minutes.
Functional connectivity (z-score) between the left anterior insula and superior frontal gyrus were measured during administration of subanesthetic nitrous oxide.
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|---|---|---|
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Tonic Stimulus Intensity During Nitrous Oxide
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4.9688 score on a scale
Standard Deviation 1.217
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2.500 score on a scale
Standard Deviation 2.309
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SECONDARY outcome
Timeframe: Baseline to 50 minutesBrain imaging data were obtained from functional magnetic resonance imaging (fMRI) data recorded simultaneously with electroencephalography (EEG) data at baseline and under a sub-anesthetic dose of nitrous oxide. Spectral data were averaged from EEG data at all electrodes collected during the baseline and sub-anesthetic dose (35%) of nitrous oxide to observe changes in spectral power. The EEG power spectrum was divided into three frequency bands: Delta = 1-3 Hz; Theta = 4-7 Hz; and Alpha = 8 - 13 Hz
Outcome measures
| Measure |
Pre-Nitrous
n=16 Participants
Each volunteer will participate in one scanning visit in which simultaneous fMRI/EEG data will be collected as they receive oxygen (20 minutes) followed
Functional connectivity (Fisher's r to z transformed) between the left anterior insula and superior frontal gyrus were measured at baseline.
|
Nitrous Oxide - Subanesthetic Dose
n=16 Participants
Each volunteer will participate in one scanning visit in which simultaneous fMRI/EEG data will be collected as they received subanesthetic dose of nitrous oxide at (35% inhaled concentration) over 30 minutes.
Functional connectivity (z-score) between the left anterior insula and superior frontal gyrus were measured during administration of subanesthetic nitrous oxide.
|
|---|---|---|
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Spectral Power of Sub-anesthetic Dose of Nitrous Oxide
Delta
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13.31 dB (decibels)
Standard Deviation 2.20
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14.65 dB (decibels)
Standard Deviation 2.56
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Spectral Power of Sub-anesthetic Dose of Nitrous Oxide
Theta
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11.88 dB (decibels)
Standard Deviation 1.89
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12.80 dB (decibels)
Standard Deviation 1.87
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Spectral Power of Sub-anesthetic Dose of Nitrous Oxide
Alpha
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6.72 dB (decibels)
Standard Deviation 1.92
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6.97 dB (decibels)
Standard Deviation 2.05
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Adverse Events
Nitrous Oxide - Inhaled
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Nitrous Oxide - Inhaled
n=19 participants at risk
Each volunteer will participate in one scanning visit in which simultaneous fMRI/EEG data will be collected wherein they receive placebo (20 minutes) followed by inhaled nitrous oxide at subanalgesic levels (35% inhaled concentration) over 30 minutes.
A total of 21 participants consented to participate but 2 participants did not participate in any part of the research and thus no adverse events data could have been collected.
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|---|---|
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General disorders
Tachycardia
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5.3%
1/19 • Number of events 1 • Adverse event data was collected for 24 hours.
The definition of adverse event and/or serious adverse event does not differ from the clinicaltrials.gov definition.
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General disorders
Emesis
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5.3%
1/19 • Number of events 1 • Adverse event data was collected for 24 hours.
The definition of adverse event and/or serious adverse event does not differ from the clinicaltrials.gov definition.
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Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place