Schizophrenia Spectrum
Conditions
Keywords
Psychosis, Schizophrenia, Oxytocin
Brief summary
This study will evaluate the effect of 8 doses of intranasal oxytocin or placebo on two proposed measures of target engagement in brain. The targets are (1) the suppression of a particular wave form (mu) on the electroencephalogram (EEG) while subjects observe a socially relevant form of motion and (2) pupil dilation will subjects identify faces showing different emotions.
Detailed description
Subjects with schizophrenia spectrum disorders will be randomly assigned to one of 8 doses of oxytocin. After screening and informed consent subjects will receive either their assigned dose or a placebo. Thirty minutes following the drug administration patients will be evaluated on the EEG and pupillometry tasks followed by two tests that evaluate social salience. One week later subjects will have a second challenge in the alternative (drug or placebo) condition.
Interventions
DRUGIntranasal Oxytocin
Sponsors
University of California, Los Angeles
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Schizophrenia, Schizoaffective Disorder, Delusional Disorder * Able to cooperate with study procedures
Exclusion criteria
* Serious medical condition or substance use * Pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mu Suppression on EEG | Baseline, 1 Week | This primary outcome measure is mu suppression recorded during a biological motion task. In this task, participants view point-light walker (PLW) animations of a human; the PLWs were either male or female, happy or sad, or walking towards or away from the viewer. In addition to the humans, there was a control condition which consisted of a circle moving either left or right. In separate blocks, participants had to identify either the gender, the emotion, or intention (i.e., direction) of the walker, or the direction of the circle, while their EEG was recorded. The primary measure was mu activity (8-12 Hz) recorded over 3 central electrodes. Mu suppression was calculated as the log10 transformed ratio of mu power to one of the three human conditions compared to the circle: log10(human/circle). A negative value indicates suppression of mu activity to human walkers vs. circles. We are presenting the mean (SD) of this suppression ratio collapsed over the 3 human conditions. |
| Pupil Dilation While Observing Faces | Baseline, 1 Week | This primary outcome measure is pupil size recorded during a facial affect identification task. In this task, participants view faces portraying happy, afraid, or neutral faces; scrambled images of the faces were also shown. There were 64 trials: 16 trials per each image type. The primary measure was the difference in pupil size averaged over the happy and fearful faces from the scrambled face condition. A positive value indicates greater pupil dilation relative to the scrambled face; a negative value indicates greater pupil constriction relative to the scrambled face. Baseline was defined as the median pupil width 1 second prior to stimulus onset. Pupil sizes during each trial were baseline-corrected by dividing them by baseline median width. Resulting pupil size timecourses were averaged within-subject for each type of stimulus (happy, afraid, neutral, scrambled). The primary dependent variable was computed by taking the average of the change in pupil size between 1 and 3 s. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 8IU Oxytocin Subjects received either the assigned Oxytocin dose or placebo 30 minutes prior to study assessments, and a second challenge in the alternative (drug or placebo) condition one week later. | 5 |
| 12IU Oxytocin Subjects received either the assigned Oxytocin dose or placebo 30 minutes prior to study assessments, and a second challenge in the alternative (drug or placebo) condition one week later. | 6 |
| 24IU Oxytocin Subjects received either the assigned Oxytocin dose or placebo 30 minutes prior to study assessments, and a second challenge in the alternative (drug or placebo) condition one week later. | 6 |
| 36IU Oxytocin Subjects received either the assigned Oxytocin dose or placebo 30 minutes prior to study assessments, and a second challenge in the alternative (drug or placebo) condition one week later. | 6 |
| 48IU Oxytocin Subjects received either the assigned Oxytocin dose or placebo 30 minutes prior to study assessments, and a second challenge in the alternative (drug or placebo) condition one week later. | 6 |
| 60IU Oxytocin Subjects received either the assigned Oxytocin dose or placebo 30 minutes prior to study assessments, and a second challenge in the alternative (drug or placebo) condition one week later. | 6 |
| 72IU Oxytocin Subjects received either the assigned Oxytocin dose or placebo 30 minutes prior to study assessments, and a second challenge in the alternative (drug or placebo) condition one week later. | 6 |
| 84IU Oxytocin Subjects received either the assigned Oxytocin dose or placebo 30 minutes prior to study assessments, and a second challenge in the alternative (drug or placebo) condition one week later. | 6 |
| Total | 47 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Did not show for testing | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Equipment failure | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | 8IU Oxytocin | 12IU Oxytocin | 24IU Oxytocin | 36IU Oxytocin | 48IU Oxytocin | 60IU Oxytocin | 72IU Oxytocin | 84IU Oxytocin | Total |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 44.6 Years STANDARD_DEVIATION 8.1 | 45.3 Years STANDARD_DEVIATION 9.2 | 42.2 Years STANDARD_DEVIATION 11.9 | 45.5 Years STANDARD_DEVIATION 8.7 | 43.3 Years STANDARD_DEVIATION 10 | 45.2 Years STANDARD_DEVIATION 9.8 | 37.2 Years STANDARD_DEVIATION 11.3 | 43.0 Years STANDARD_DEVIATION 9.8 | 42.9 Years STANDARD_DEVIATION 9.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 3 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants | 1 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 3 Participants | 5 Participants | 6 Participants | 5 Participants | 5 Participants | 4 Participants | 5 Participants | 37 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 1 Participants | 2 Participants | 5 Participants | 1 Participants | 2 Participants | 3 Participants | 2 Participants | 19 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 4 Participants | 3 Participants | 1 Participants | 4 Participants | 4 Participants | 2 Participants | 4 Participants | 23 Participants |
| Region of Enrollment United States | 5 participants | 6 participants | 6 participants | 6 participants | 6 participants | 6 participants | 6 participants | 6 participants | 47 participants |
| Sex: Female, Male Female | 2 Participants | 3 Participants | 2 Participants | 2 Participants | 3 Participants | 1 Participants | 1 Participants | 2 Participants | 16 Participants |
| Sex: Female, Male Male | 3 Participants | 3 Participants | 4 Participants | 4 Participants | 3 Participants | 5 Participants | 5 Participants | 4 Participants | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 47 |
| other Total, other adverse events | 0 / 5 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 47 |
| serious Total, serious adverse events | 0 / 5 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 47 |
Outcome results
Primary
Mu Suppression on EEG
This primary outcome measure is mu suppression recorded during a biological motion task. In this task, participants view point-light walker (PLW) animations of a human; the PLWs were either male or female, happy or sad, or walking towards or away from the viewer. In addition to the humans, there was a control condition which consisted of a circle moving either left or right. In separate blocks, participants had to identify either the gender, the emotion, or intention (i.e., direction) of the walker, or the direction of the circle, while their EEG was recorded. The primary measure was mu activity (8-12 Hz) recorded over 3 central electrodes. Mu suppression was calculated as the log10 transformed ratio of mu power to one of the three human conditions compared to the circle: log10(human/circle). A negative value indicates suppression of mu activity to human walkers vs. circles. We are presenting the mean (SD) of this suppression ratio collapsed over the 3 human conditions.
Time frame: Baseline, 1 Week
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 8IU Oxytocin | Mu Suppression on EEG | -0.0907 log10 transformed ratio (Hz) | Standard Deviation 0.10515 |
| 12IU Oxytocin | Mu Suppression on EEG | -0.0632 log10 transformed ratio (Hz) | Standard Deviation 0.08206 |
| 24IU Oxytocin | Mu Suppression on EEG | -0.0542 log10 transformed ratio (Hz) | Standard Deviation 0.07471 |
| 36IU Oxytocin | Mu Suppression on EEG | -0.1153 log10 transformed ratio (Hz) | Standard Deviation 0.07699 |
| 48IU Oxytocin | Mu Suppression on EEG | -0.1333 log10 transformed ratio (Hz) | Standard Deviation 0.06625 |
| 60IU Oxytocin | Mu Suppression on EEG | -0.0459 log10 transformed ratio (Hz) | Standard Deviation 0.03514 |
| 72IU Oxytocin | Mu Suppression on EEG | -0.1101 log10 transformed ratio (Hz) | Standard Deviation 0.02654 |
| 84IU Oxytocin | Mu Suppression on EEG | -0.0149 log10 transformed ratio (Hz) | Standard Deviation 0.08074 |
| Placebo | Mu Suppression on EEG | -0.0726 log10 transformed ratio (Hz) | Standard Deviation 0.10331 |
Primary
Pupil Dilation While Observing Faces
This primary outcome measure is pupil size recorded during a facial affect identification task. In this task, participants view faces portraying happy, afraid, or neutral faces; scrambled images of the faces were also shown. There were 64 trials: 16 trials per each image type. The primary measure was the difference in pupil size averaged over the happy and fearful faces from the scrambled face condition. A positive value indicates greater pupil dilation relative to the scrambled face; a negative value indicates greater pupil constriction relative to the scrambled face. Baseline was defined as the median pupil width 1 second prior to stimulus onset. Pupil sizes during each trial were baseline-corrected by dividing them by baseline median width. Resulting pupil size timecourses were averaged within-subject for each type of stimulus (happy, afraid, neutral, scrambled). The primary dependent variable was computed by taking the average of the change in pupil size between 1 and 3 s.
Time frame: Baseline, 1 Week
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 8IU Oxytocin | Pupil Dilation While Observing Faces | .0074 arbitrary units | Standard Deviation 0.00669 |
| 12IU Oxytocin | Pupil Dilation While Observing Faces | .0347 arbitrary units | Standard Deviation 0.03395 |
| 24IU Oxytocin | Pupil Dilation While Observing Faces | -.0089 arbitrary units | Standard Deviation 4525 |
| 36IU Oxytocin | Pupil Dilation While Observing Faces | .0153 arbitrary units | Standard Deviation 0.02317 |
| 48IU Oxytocin | Pupil Dilation While Observing Faces | -.0011 arbitrary units | Standard Deviation 0.02862 |
| 60IU Oxytocin | Pupil Dilation While Observing Faces | .0103 arbitrary units | Standard Deviation 0.01498 |
| 72IU Oxytocin | Pupil Dilation While Observing Faces | .0299 arbitrary units | Standard Deviation 0.03634 |
| 84IU Oxytocin | Pupil Dilation While Observing Faces | .0073 arbitrary units | Standard Deviation 0.03469 |
| Placebo | Pupil Dilation While Observing Faces | .0134 arbitrary units | Standard Deviation 0.03195 |