Trial Outcomes & Findings for Intranasal Oxytocin Administration and the Neural Correlates of Social and Non-Social Visual Perception (NCT NCT02238379)

Results Overview

The investigators will analyze the amplitude (i.e., size) of visually elicited event-related potential (ERP) components to the social stimuli (infant and adult faces). This assessment will be completed after administration of the intervention (oxytocin) and the placebo to compare the neural response. The investigators hypothesize that the intervention will modulate the amplitude of the neural response to social stimuli given its previously identified role in social interactions, most likely increasing the size of the ERPs.

Recruitment status

COMPLETED

Study phase

EARLY_PHASE1

Target enrollment

26 participants

Primary outcome timeframe

Duration of 30 minutes

Results posted on

2018-01-17

Participant Flow

Participant milestones

Participant milestones
Measure	Oxytocin First, Then Placebo Each participant will receive both the oxytocin nasal spray in one visit AND the placebo nasal spray in another visit (randomized) in this design. Oxytocin: 24 International Units of Oxytocin in a Nasal Spray	Placebo First, Then Oxytocin Each participant will receive both the oxytocin nasal spray in one visit AND the placebo nasal spray in another visit (randomized) in this design. Placebo: Placebo will contain all ingredients except the active oxytocin in the Nasal Spray.
Overall Study STARTED	12	14
Overall Study COMPLETED	11	14
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Oxytocin First, Then Placebo Each participant will receive both the oxytocin nasal spray in one visit AND the placebo nasal spray in another visit (randomized) in this design. Oxytocin: 24 International Units of Oxytocin in a Nasal Spray	Placebo First, Then Oxytocin Each participant will receive both the oxytocin nasal spray in one visit AND the placebo nasal spray in another visit (randomized) in this design. Placebo: Placebo will contain all ingredients except the active oxytocin in the Nasal Spray.
Overall Study Lost to Follow-up	1	0

Baseline Characteristics

Intranasal Oxytocin Administration and the Neural Correlates of Social and Non-Social Visual Perception

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Oxytocin n=12 Participants Each participant will receive both the oxytocin nasal spray in one visit AND the placebo nasal spray in another visit (randomized) in this design. Oxytocin: 24 International Units of Oxytocin in a Nasal Spray	Placebo n=14 Participants Each participant will receive both the oxytocin nasal spray in one visit AND the placebo nasal spray in another visit (randomized) in this design. Placebo: Placebo will contain all ingredients except the active oxytocin in the Nasal Spray.	Total n=26 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	12 Participants n=5 Participants	14 Participants n=7 Participants	26 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	24 years STANDARD_DEVIATION 3 • n=5 Participants	23 years STANDARD_DEVIATION 3 • n=7 Participants	24 years STANDARD_DEVIATION 3 • n=5 Participants
Sex: Female, Male Female	12 Participants n=5 Participants	14 Participants n=7 Participants	26 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	12 participants n=5 Participants	14 participants n=7 Participants	26 participants n=5 Participants

PRIMARY outcome

Timeframe: Duration of 30 minutes

Population: 1 participant was lost to follow-up (did not complete placebo); 1 participant's data was lost (removed then from placebo and oxytocin arms); for LPP analysis, 1 participant was a statistical outlier and removed from oxytocin and placebo arms

The investigators will analyze the amplitude (i.e., size) of visually elicited event-related potential (ERP) components to the social stimuli (infant and adult faces). This assessment will be completed after administration of the intervention (oxytocin) and the placebo to compare the neural response. The investigators hypothesize that the intervention will modulate the amplitude of the neural response to social stimuli given its previously identified role in social interactions, most likely increasing the size of the ERPs.

Outcome measures

Outcome measures
Measure	Oxytocin n=24 Participants Each participant will receive both the oxytocin nasal spray in one visit AND the placebo nasal spray in another visit (randomized) in this design. Oxytocin: 24 International Units of Oxytocin in a Nasal Spray	Placebo n=24 Participants Each participant will receive both the oxytocin nasal spray in one visit AND the placebo nasal spray in another visit (randomized) in this design. Placebo: Placebo will contain all ingredients except the active oxytocin in the Nasal Spray.
Amplitude Social LPP Adult Distress Face	-0.38 microvolts Standard Deviation 1.33	-0.57 microvolts Standard Deviation 1.40
Amplitude Social LPP Adult Neutral Face	-0.71 microvolts Standard Deviation 1.49	-0.40 microvolts Standard Deviation 1.27
Amplitude Social N170 Infant Distress Faces	-3.72 microvolts Standard Deviation 2.81	-3.55 microvolts Standard Deviation 2.64
Amplitude Social N170 Infant Neutral	-3.28 microvolts Standard Deviation 2.55	-3.30 microvolts Standard Deviation 2.94
Amplitude Social N170 Adult Distress	-3.70 microvolts Standard Deviation 2.72	-3.27 microvolts Standard Deviation 2.64
Amplitude Social N170 Adult Neutral	-3.23 microvolts Standard Deviation 2.48	-2.87 microvolts Standard Deviation 2.33
Amplitude Social P300 Infant Distress Face	0.94 microvolts Standard Deviation 1.26	0.50 microvolts Standard Deviation 1.21
Amplitude Social P300 Infant Neutral Face	1.10 microvolts Standard Deviation 1.47	0.55 microvolts Standard Deviation 1.34
Amplitude Social P300 Adult Distress Face	0.65 microvolts Standard Deviation 1.22	0.39 microvolts Standard Deviation 0.91
Amplitude Social P300 Adult Neutral Face	0.52 microvolts Standard Deviation 1.38	0.61 microvolts Standard Deviation 1.09
Amplitude Social LPP Infant Distress Face	-0.56 microvolts Standard Deviation 1.53	-0.50 microvolts Standard Deviation 0.94
Amplitude Social LPP Infant Neutral Face	-0.24 microvolts Standard Deviation 1.40	-0.54 microvolts Standard Deviation 1.51

PRIMARY outcome

Timeframe: Duration of 30 minutes

Population: 1 participant was lost to follow-up (did not complete placebo); 1 participant's data was lost (removed then from placebo and oxytocin arms)

The investigators analyze the amplitude (i.e., size) of visually elicited event-related potential (ERP) components to the non-social stimuli (houses). This assessment will be completed after administration of the intervention (oxytocin) and the placebo to compare the neural response. The investigators hypothesize that there will be no difference between the intervention and placebo during the non-social condition on the amplitude of the ERPs.

Outcome measures

Outcome measures
Measure	Oxytocin n=24 Participants Each participant will receive both the oxytocin nasal spray in one visit AND the placebo nasal spray in another visit (randomized) in this design. Oxytocin: 24 International Units of Oxytocin in a Nasal Spray	Placebo n=24 Participants Each participant will receive both the oxytocin nasal spray in one visit AND the placebo nasal spray in another visit (randomized) in this design. Placebo: Placebo will contain all ingredients except the active oxytocin in the Nasal Spray.
Amplitude Non-Social N170 House	-1.15 microvolts Standard Deviation 1.71	-1.15 microvolts Standard Deviation 1.35
Amplitude Non-Social P300 House	1.21 microvolts Standard Deviation 1.47	0.86 microvolts Standard Deviation 0.91
Amplitude Non-Social LPP House	-0.58 microvolts Standard Deviation 1.12	-0.32 microvolts Standard Deviation 1.06

PRIMARY outcome

Timeframe: Duration of 30 minutes

Population: 1 participant was lost to follow-up (did not complete placebo); 1 participant's data was lost (removed then from placebo and oxytocin arms); for LPP analysis, 1 participants were statistical outliers and removed from oxytocin and placebo arms for N170 latency analysis

The investigators analyze the latency (i.e., efficiency of processing) of visually elicited ERP components to the social stimuli (infant and adult faces). This assessment will be completed after administration of the intervention (oxytocin) and the placebo to compare the neural response. The investigators hypothesize that there will be more efficient processing (i.e., earlier latency) of ERPs during the social condition following administration of the intervention relative to the placebo condition.

Outcome measures

Outcome measures
Measure	Oxytocin n=23 Participants Each participant will receive both the oxytocin nasal spray in one visit AND the placebo nasal spray in another visit (randomized) in this design. Oxytocin: 24 International Units of Oxytocin in a Nasal Spray	Placebo n=23 Participants Each participant will receive both the oxytocin nasal spray in one visit AND the placebo nasal spray in another visit (randomized) in this design. Placebo: Placebo will contain all ingredients except the active oxytocin in the Nasal Spray.
Latency Social Right N170 Adult Distress	162 milliseconds Standard Deviation 9	161 milliseconds Standard Deviation 9
Latency Social N170 Infant Distress	164 milliseconds Standard Deviation 8	164 milliseconds Standard Deviation 10
Latency Social N170 Infant Neutral	163 milliseconds Standard Deviation 9	161 milliseconds Standard Deviation 9
Latency Social N170 Adult Distress	164 milliseconds Standard Deviation 10	163 milliseconds Standard Deviation 12
Latency Social N170 Adult Neutral	161 milliseconds Standard Deviation 9	161 milliseconds Standard Deviation 11
Latency Social Left N170 Infant Distress	165 milliseconds Standard Deviation 9	166 milliseconds Standard Deviation 10
Latency Social Right N170 Infant Distress	164 milliseconds Standard Deviation 8	162 milliseconds Standard Deviation 9
Latency Social Left N170 Infant Neutral	165 milliseconds Standard Deviation 11	163 milliseconds Standard Deviation 10
Latency Social Right N170 Infant Neutral	161 milliseconds Standard Deviation 7	160 milliseconds Standard Deviation 9
Latency Social Left N170 Adult Distress	166 milliseconds Standard Deviation 11	165 milliseconds Standard Deviation 14
Latency Social Left N170 Adult Neutral	163 milliseconds Standard Deviation 10	162 milliseconds Standard Deviation 13
Latency Social Right N170 Adult Neutral	159 milliseconds Standard Deviation 8	160 milliseconds Standard Deviation 10

PRIMARY outcome

Timeframe: Duration of 30 minutes

Population: 1 participant was lost to follow-up (did not complete placebo); 1 participant's data was lost (removed then from placebo and oxytocin arms); 2 participants were statistical outliers and removed from oxytocin and placebo arms for N170 latency analysis

The investigators will analyze the latency (i.e., efficiency of processing) of visually elicited ERP components to the non-social stimuli (houses). This assessment will be completed after administration of the intervention (oxytocin) and the placebo to compare the neural response. The investigators hypothesize that there will be no difference between the intervention and placebo on ERP latency measures in the non-social condition.

Outcome measures

Outcome measures
Measure	Oxytocin n=23 Participants Each participant will receive both the oxytocin nasal spray in one visit AND the placebo nasal spray in another visit (randomized) in this design. Oxytocin: 24 International Units of Oxytocin in a Nasal Spray	Placebo n=23 Participants Each participant will receive both the oxytocin nasal spray in one visit AND the placebo nasal spray in another visit (randomized) in this design. Placebo: Placebo will contain all ingredients except the active oxytocin in the Nasal Spray.
Latency Non-Social Left N170 House	171 milliseconds Standard Deviation 13	174 milliseconds Standard Deviation 14
Latency Non-Social Right N170 House	166 milliseconds Standard Deviation 9	169 milliseconds Standard Deviation 13

SECONDARY outcome

Timeframe: Within 20 minutes of study visit commencing

Population: Only participants included that have ERP data to analyze (excluding participant lost to follow-up and data loss)

The investigators will assess depression by employing the Beck Depression Inventory (Beck et al., 1961). Specifically addressing whether the level of depression symptomatology in participants and whether this is associated with the neural correlates of social and non-social perception during both intervention and placebo visits. It is not yet known the extent to which variation in depression symptoms are associated with this methodology, although prior research has suggested depression modulates the neural response to social cues. This measure includes a question regarding suicidal ideation and therefore it is acknowledged there may be a safety issue in response to the questionnaire. Scores range from 0-63, with higher scores indicating greater levels of depression (scores 29+ indicates severe depression).

Outcome measures

Outcome measures
Measure	Oxytocin n=24 Participants Each participant will receive both the oxytocin nasal spray in one visit AND the placebo nasal spray in another visit (randomized) in this design. Oxytocin: 24 International Units of Oxytocin in a Nasal Spray	Placebo n=24 Participants Each participant will receive both the oxytocin nasal spray in one visit AND the placebo nasal spray in another visit (randomized) in this design. Placebo: Placebo will contain all ingredients except the active oxytocin in the Nasal Spray.
Depression	4.00 units on a scale Standard Deviation 6.06	4.33 units on a scale Standard Deviation 5.75

SECONDARY outcome

Timeframe: Within 30 minutes of study visit commencing

Population: 1 participant was lost to follow-up

Participants will complete a CO breathalyzer and the Fagerstrom Test for Nicotine Dependence (Heatherton, Kozlowski, Frecker, \& Fagerstrom, 1991) to assess smoking behavior. These measures are included to characterize the sample in respect of substance use.

Outcome measures

Outcome measures
Measure	Oxytocin n=26 Participants Each participant will receive both the oxytocin nasal spray in one visit AND the placebo nasal spray in another visit (randomized) in this design. Oxytocin: 24 International Units of Oxytocin in a Nasal Spray	Placebo n=25 Participants Each participant will receive both the oxytocin nasal spray in one visit AND the placebo nasal spray in another visit (randomized) in this design. Placebo: Placebo will contain all ingredients except the active oxytocin in the Nasal Spray.
Smoking FTND indicated smoking status	1 Participants	0 Participants
Smoking CO indicated smoking status	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Within 20 minutes of study visit commencing

Population: Only participants included that have ERP data to analyze (excluding participant lost to follow-up and data loss)

The investigators will assess anxiety using the State-Trait Anxiety Inventory (Spielberger et al., 1970). Specifically, it will be explored whether participant anxiety symptoms are associated with the neural correlates of social and non-social perception during both intervention and placebo visits. It is not yet known the extent to which variation in anxiety symptoms are associated with this methodology, although prior research has suggested anxiety modulates the neural response to social cues. Scores range from 20-80 and a higher score on both state and trait measures indicate higher levels of anxiety. A potential clinical cut off has been proposed for participants scoring over 39-40 as being high anxious.

Outcome measures

Outcome measures
Measure	Oxytocin n=24 Participants Each participant will receive both the oxytocin nasal spray in one visit AND the placebo nasal spray in another visit (randomized) in this design. Oxytocin: 24 International Units of Oxytocin in a Nasal Spray	Placebo n=24 Participants Each participant will receive both the oxytocin nasal spray in one visit AND the placebo nasal spray in another visit (randomized) in this design. Placebo: Placebo will contain all ingredients except the active oxytocin in the Nasal Spray.
Anxiety State Anxiety	31.54 units on a scale Standard Deviation 10.67	35.50 units on a scale Standard Deviation 11.27
Anxiety Trait Anxiety	30.58 units on a scale Standard Deviation 10.11	30.79 units on a scale Standard Deviation 7.82

SECONDARY outcome

Timeframe: Within 20 minutes of study visit commencing

Population: Only participants included that have ERP data to analyze (excluding participant lost to follow-up and data loss)

The investigators will measure current levels of stress by using the Perceived Stress Scale (Cohen et al., 1983). It is not yet known the extent to which variation in perceived stress is associated with this methodology, but it is anticipated stress will be associated with levels of depression and anxiety in the sample. The PSS consists of 14 items, with scores ranging from 0 to 42, with higher scores indicating higher levels of perceived stress. A score of 21+ is considered to indicate that participants have higher than average stress.

Outcome measures

Outcome measures
Measure	Oxytocin n=24 Participants Each participant will receive both the oxytocin nasal spray in one visit AND the placebo nasal spray in another visit (randomized) in this design. Oxytocin: 24 International Units of Oxytocin in a Nasal Spray	Placebo n=24 Participants Each participant will receive both the oxytocin nasal spray in one visit AND the placebo nasal spray in another visit (randomized) in this design. Placebo: Placebo will contain all ingredients except the active oxytocin in the Nasal Spray.
Stress	17.54 units on a scale Standard Deviation 8.28	18.13 units on a scale Standard Deviation 8.23

SECONDARY outcome

Timeframe: Within 20 minutes of study visit commencing

Population: Only participants included that have ERP data to analyze (excluding participant lost to follow-up and data loss); 1 participant did not know their father and did not complete the measure for paternal assessment

The investigators will employ the Parental Bonding Instrument (Parker, Tupling, \& Brown, 1979) to assess the early relationship experiences participants have with their caregivers. Existing research employing intranasal oxytocin suggests that the quality of early relationships may impact the strength of any modulation of brain or behavior by oxytocin administration and therefore this variable will be included in the analyses in support of this hypothesis. There are 12 items that capture parental care and 13 items that capture parental overprotection. Items are scored on a 4-point likert scale from "very like" to "very unlike". The PBI is typically scored by identifying optimal (High Care Scores, Low Protection Scores) and less optimal (Low Care Scores, Low Protection Scores) scores on the mother and father subscales (NB: protection refers to overprotection). For the care items, scores can range from 0 to 36; for overprotection items, scores can range from 0 to 39.

Outcome measures

Outcome measures
Measure	Oxytocin n=24 Participants Each participant will receive both the oxytocin nasal spray in one visit AND the placebo nasal spray in another visit (randomized) in this design. Oxytocin: 24 International Units of Oxytocin in a Nasal Spray	Placebo n=24 Participants Each participant will receive both the oxytocin nasal spray in one visit AND the placebo nasal spray in another visit (randomized) in this design. Placebo: Placebo will contain all ingredients except the active oxytocin in the Nasal Spray.
Early Experience Maternal Care Score	30.13 units on a scale Standard Deviation 6.69	29.50 units on a scale Standard Deviation 6.79
Early Experience Paternal Care Score	27.74 units on a scale Standard Deviation 8.67	28.13 units on a scale Standard Deviation 8.95
Early Experience Maternal Protectiveness Score	13.71 units on a scale Standard Deviation 8.01	13.75 units on a scale Standard Deviation 8.51
Early Experience Paternal Protectiveness Score	11.91 units on a scale Standard Deviation 8.30	10.91 units on a scale Standard Deviation 9.34

SECONDARY outcome

Timeframe: Within 30 minutes of study visit commencing

Population: 1 participant lost to follow-up; count of participants where substance dependence indicated

The investigators will employ the ASI Lite (McLellan, Luborsky, Woody, \& O'Brien, 1980) to assess for current substance use. This measure is included to characterize the sample in respect of substance use; however the ASI Lite did not provide a measure of substance dependance and therefore we report the data from the Mini International Neuropsychiatric Interview substance dependance module (Sheehan et al., 1998) to provide a specific indication of the presence of absence of substance dependance.

Outcome measures

Outcome measures
Measure	Oxytocin n=11 Participants Each participant will receive both the oxytocin nasal spray in one visit AND the placebo nasal spray in another visit (randomized) in this design. Oxytocin: 24 International Units of Oxytocin in a Nasal Spray	Placebo n=14 Participants Each participant will receive both the oxytocin nasal spray in one visit AND the placebo nasal spray in another visit (randomized) in this design. Placebo: Placebo will contain all ingredients except the active oxytocin in the Nasal Spray.
Number of Participants Endorsing Substance Use	0 Participants	2 Participants

SECONDARY outcome

Timeframe: Within 30 minutes of study visit commencing

Population: 1 participant lost to follow-up; data indicates number of participants with alcohol in their system

Participants will complete an alcohol breathalyzer to characterize the alcohol use status of the sample.

Outcome measures

Outcome measures
Measure	Oxytocin n=11 Participants Each participant will receive both the oxytocin nasal spray in one visit AND the placebo nasal spray in another visit (randomized) in this design. Oxytocin: 24 International Units of Oxytocin in a Nasal Spray	Placebo n=14 Participants Each participant will receive both the oxytocin nasal spray in one visit AND the placebo nasal spray in another visit (randomized) in this design. Placebo: Placebo will contain all ingredients except the active oxytocin in the Nasal Spray.
Number of Participants Testing Positive for Alcohol Use Following a Breathalyzer	0 Participants	0 Participants

Adverse Events

Oxytocin

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Helena Rutherford

Yale University

Phone: 203-737-3408

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place