Trial Outcomes & Findings for Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders (NCT NCT02940574)

Results Overview

Change From Baseline in Task-related Brain Activity During Biological Motion Recognition Task (Task-based fMRI) After a Single Dose of Nasal Spray BOLD response (Blood-oxygen-level-dependent response)

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

40 participants

Primary outcome timeframe

Value at 30 minutes minus value at baseline

Results posted on

2021-02-10

Participant Flow

Participants were mainly recruited from the Expertise Centrum Autisme of the UZ Leuven between April 2015 and December 2016. Recruitment and patient contact were facilitated by our collaboration with Prof. Dr. Jean Steyaert, head of UZ Leuven ECA.

Participant milestones

Participant milestones
Measure	Syntocinon (Oxytocin, Product Code RVG 03716) Administration via nasal spray Syntocinon (Oxytocin): Syntocinon nasal spray. A single dose (24IU) of nasal spray (3 puffs of 4IU per nostril), followed by 4 weeks of a daily single dose (24IU; 3 puffs of 4IU per nostril) of nasal spray	Placebo (Physiological Water(Sodium Chloride (NaCl) Solution)) Administration via nasal spray Placebo (Physiological water (solution of sodium chloride (NaCl) in water)): Placebo nasal spray. A single dose (24IU) of nasal spray (3 puffs of 4IU per nostril), followed by 4 weeks of a daily single dose (24IU; 3 puffs of 4IU per nostril) of nasal spray
From Study Start to 1-month Follow-up STARTED	22	18
From Study Start to 1-month Follow-up COMPLETED	21	18
From Study Start to 1-month Follow-up NOT COMPLETED	1	0
1-year Follow-up STARTED	21	18
1-year Follow-up COMPLETED	18	14
1-year Follow-up NOT COMPLETED	3	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Syntocinon (Oxytocin, Product Code RVG 03716) Administration via nasal spray Syntocinon (Oxytocin): Syntocinon nasal spray. A single dose (24IU) of nasal spray (3 puffs of 4IU per nostril), followed by 4 weeks of a daily single dose (24IU; 3 puffs of 4IU per nostril) of nasal spray	Placebo (Physiological Water(Sodium Chloride (NaCl) Solution)) Administration via nasal spray Placebo (Physiological water (solution of sodium chloride (NaCl) in water)): Placebo nasal spray. A single dose (24IU) of nasal spray (3 puffs of 4IU per nostril), followed by 4 weeks of a daily single dose (24IU; 3 puffs of 4IU per nostril) of nasal spray
From Study Start to 1-month Follow-up Withdrawal by Subject	1	0
1-year Follow-up Lost to Follow-up	3	4

Baseline Characteristics

Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Syntocinon (Oxytocin, Product Code RVG 03716) n=22 Participants Administration via nasal spray Syntocinon (Oxytocin): Syntocinon nasal spray. A single dose (24IU) of nasal spray (3 puffs of 4IU per nostril), followed by 4 weeks of a daily single dose (24IU; 3 puffs of 4IU per nostril) of nasal spray	Placebo (Physiological Water(Sodium Chloride (NaCl) Solution)) n=18 Participants Administration via nasal spray Placebo (Physiological water (solution of sodium chloride (NaCl) in water)): Placebo nasal spray. A single dose (24IU) of nasal spray (3 puffs of 4IU per nostril), followed by 4 weeks of a daily single dose (24IU; 3 puffs of 4IU per nostril) of nasal spray	Total n=40 Participants Total of all reporting groups
Age, Continuous	25.00 years STANDARD_DEVIATION 4.86 • n=5 Participants	24.00 years STANDARD_DEVIATION 5.55 • n=7 Participants	24.38 years STANDARD_DEVIATION 5.11 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	22 Participants n=5 Participants	18 Participants n=7 Participants	40 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	22 Participants n=5 Participants	18 Participants n=7 Participants	40 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment Belgium	22 participants n=5 Participants	18 participants n=7 Participants	38 participants n=5 Participants
Total IQ	102.27 units on a scale STANDARD_DEVIATION 12.45 • n=5 Participants	104.61 units on a scale STANDARD_DEVIATION 21.59 • n=7 Participants	104.24 units on a scale STANDARD_DEVIATION 15.72 • n=5 Participants

PRIMARY outcome

Timeframe: Value at 30 minutes minus value at baseline

Population: 1 subject lost in Syntocinon group due to subject withdrawal. 1 subject lost in Placebo group due to low data quality (excessive in-scanner head motion)

Change From Baseline in Task-related Brain Activity During Biological Motion Recognition Task (Task-based fMRI) After a Single Dose of Nasal Spray BOLD response (Blood-oxygen-level-dependent response)

Outcome measures

Outcome measures
Measure	Syntocinon (Oxytocin, Product Code RVG 03716) n=21 Participants Administration via nasal spray Syntocinon (Oxytocin): Syntocinon nasal spray. A single dose (24IU) of nasal spray (3 puffs of 4IU per nostril).	Placebo (Physiological Water(Sodium Chloride (NaCl) Solution)) n=17 Participants Administration via nasal spray Placebo (Physiological water (solution of sodium chloride (NaCl) in water)): Placebo nasal spray.
Change From Baseline in Brain Activity During Task (Task-based fMRI) After a Single Dose of Nasal Spray Brain activity - Superior temporal sulcus	0.11 Change-from-baseline (BOLD response) Standard Deviation 0.49	-0.26 Change-from-baseline (BOLD response) Standard Deviation 0.72
Change From Baseline in Brain Activity During Task (Task-based fMRI) After a Single Dose of Nasal Spray Brain activity - Amygdala	-0.15 Change-from-baseline (BOLD response) Standard Deviation 0.50	-0.16 Change-from-baseline (BOLD response) Standard Deviation 0.58

PRIMARY outcome

Timeframe: Value at 4 weeks minus value at baseline

Population: 1 subject lost in Syntocinon group due to subject withdrawal. 1 subject lost in Placebo group due to low data quality (excessive in-scanner head motion)

Change From Baseline in Task-related Brain Activity During Biological Motion Recognition Task (Task-based fMRI) after 4 weeks of nasal spray BOLD response (Blood-oxygen-level-dependent response)

Outcome measures

Outcome measures
Measure	Syntocinon (Oxytocin, Product Code RVG 03716) n=21 Participants Administration via nasal spray Syntocinon (Oxytocin): Syntocinon nasal spray. A single dose (24IU) of nasal spray (3 puffs of 4IU per nostril).	Placebo (Physiological Water(Sodium Chloride (NaCl) Solution)) n=17 Participants Administration via nasal spray Placebo (Physiological water (solution of sodium chloride (NaCl) in water)): Placebo nasal spray.
Change From Baseline in Brain Activity During Task (Task-based fMRI) After 4 Weeks of Nasal Spray Brain activity - Superior temporal sulcus	-0.10 Change-from-baseline (BOLD response) Standard Deviation 0.59	-0.29 Change-from-baseline (BOLD response) Standard Deviation 0.68
Change From Baseline in Brain Activity During Task (Task-based fMRI) After 4 Weeks of Nasal Spray Brain activity - Amygdala	-0.09 Change-from-baseline (BOLD response) Standard Deviation 0.46	0.06 Change-from-baseline (BOLD response) Standard Deviation 0.45

PRIMARY outcome

Timeframe: Value at 8 weeks minus value at baseline

Population: 1 subject lost in Syntocinon group due to subject withdrawal. 1 subject lost in Placebo group due to low data quality (excessive in-scanner head motion)

Change From Baseline in Task-related Brain Activity During Biological Motion Recognition Task (Task-based fMRI) after 8 weeks, including 4 weeks without nasal spray BOLD response (Blood-oxygen-level-dependent response)

Outcome measures

Outcome measures
Measure	Syntocinon (Oxytocin, Product Code RVG 03716) n=21 Participants Administration via nasal spray Syntocinon (Oxytocin): Syntocinon nasal spray. A single dose (24IU) of nasal spray (3 puffs of 4IU per nostril).	Placebo (Physiological Water(Sodium Chloride (NaCl) Solution)) n=17 Participants Administration via nasal spray Placebo (Physiological water (solution of sodium chloride (NaCl) in water)): Placebo nasal spray.
Change From Baseline in Brain Activity During Task (Task-based fMRI) After 8 Weeks, Including 4 Weeks Without Nasal Spray Brain activity - Superior temporal sulcus	-0.21 Change-from-baseline (BOLD response) Standard Deviation 0.58	-0.16 Change-from-baseline (BOLD response) Standard Deviation 0.66
Change From Baseline in Brain Activity During Task (Task-based fMRI) After 8 Weeks, Including 4 Weeks Without Nasal Spray Brain activity - Amygdala	-0.18 Change-from-baseline (BOLD response) Standard Deviation 0.52	0.04 Change-from-baseline (BOLD response) Standard Deviation 0.56

PRIMARY outcome

Timeframe: Value at 52 weeks minus value at baseline

Population: 1 subject lost in Syntocinon group due to subject withdrawal. (+ 3 additional participants lost for 1-year follow-up) 1 subject lost in Placebo group due to low data quality (excessive in-scanner head motion) (+ 3 additional participants lost for 1-year follow-up)

Change From Baseline in Task-related Brain Activity During Biological Motion Recognition Task (Task-based fMRI) after 52 weeks, including 48 weeks without nasal spray BOLD response (Blood-oxygen-level-dependent response)

Outcome measures

Outcome measures
Measure	Syntocinon (Oxytocin, Product Code RVG 03716) n=18 Participants Administration via nasal spray Syntocinon (Oxytocin): Syntocinon nasal spray. A single dose (24IU) of nasal spray (3 puffs of 4IU per nostril).	Placebo (Physiological Water(Sodium Chloride (NaCl) Solution)) n=14 Participants Administration via nasal spray Placebo (Physiological water (solution of sodium chloride (NaCl) in water)): Placebo nasal spray.
Change From Baseline in Brain Activity During Task (Task-based fMRI) After 52 Weeks, Including 48 Weeks Without Nasal Spray Brain activity - Superior temporal sulcus	-0.18 Change-from-baseline (BOLD response) Standard Deviation 0.56	-0.48 Change-from-baseline (BOLD response) Standard Deviation 0.73
Change From Baseline in Brain Activity During Task (Task-based fMRI) After 52 Weeks, Including 48 Weeks Without Nasal Spray Brain activity - Amygdala	-0.21 Change-from-baseline (BOLD response) Standard Deviation 0.51	0.03 Change-from-baseline (BOLD response) Standard Deviation 0.40

PRIMARY outcome

Timeframe: Value at 30 minutes minus value at baseline

Population: 1 subject lost in Syntocinon group due to subject withdrawal. 1 subject lost in Placebo group due to low data quality (excessive in-scanner head motion)

Change From Baseline in Brain Connectivity During Rest (Resting-state fMRI) After a Single Dose of Nasal Spray Amygdala connectivity (Change-from-baseline z-transformed r-value) Higher z-transformed r-value indicates higher connectivity (higher correlated brain activity)

Outcome measures

Outcome measures
Measure	Syntocinon (Oxytocin, Product Code RVG 03716) n=21 Participants Administration via nasal spray Syntocinon (Oxytocin): Syntocinon nasal spray. A single dose (24IU) of nasal spray (3 puffs of 4IU per nostril).	Placebo (Physiological Water(Sodium Chloride (NaCl) Solution)) n=17 Participants Administration via nasal spray Placebo (Physiological water (solution of sodium chloride (NaCl) in water)): Placebo nasal spray.
Change From Baseline in Brain Connectivity During Rest (Resting-state fMRI) After a Single Dose of Nasal Spray	-0.07 Change-from-base z-transformed r-value Standard Deviation 0.21	0.03 Change-from-base z-transformed r-value Standard Deviation 0.20

PRIMARY outcome

Timeframe: Value at 4 weeks minus value at baseline

Population: 1 subject lost in Syntocinon group due to subject withdrawal. 1 subject lost in Placebo group due to low data quality (excessive in-scanner head motion)

Change from baseline in brain connectivity during rest (resting-state fMRI) after 4 weeks of nasal spray Amygdala connectivity (Change-from-baseline z-transformed r-value) Higher z-transformed r-value indicates higher connectivity (higher correlated brain activity)

Outcome measures

Outcome measures
Measure	Syntocinon (Oxytocin, Product Code RVG 03716) n=21 Participants Administration via nasal spray Syntocinon (Oxytocin): Syntocinon nasal spray. A single dose (24IU) of nasal spray (3 puffs of 4IU per nostril).	Placebo (Physiological Water(Sodium Chloride (NaCl) Solution)) n=17 Participants Administration via nasal spray Placebo (Physiological water (solution of sodium chloride (NaCl) in water)): Placebo nasal spray.
Change From Baseline in Brain Connectivity During Rest (Resting-state fMRI) After 4 Weeks of Nasal Spray	-0.04 Change-from-base z-transformed r-value Standard Deviation 0.22	0.11 Change-from-base z-transformed r-value Standard Deviation 0.21

PRIMARY outcome

Timeframe: Value at 8 weeks minus value at baseline

Change from baseline in brain connectivity during rest (resting-state fMRI) after 8 weeks, including 4 weeks without nasal spray Amygdala connectivity (Change-from-baseline z-transformed r-value) Higher z-transformed r-value indicates higher connectivity (higher correlated brain activity)

Outcome measures

Outcome measures
Measure	Syntocinon (Oxytocin, Product Code RVG 03716) n=21 Participants Administration via nasal spray Syntocinon (Oxytocin): Syntocinon nasal spray. A single dose (24IU) of nasal spray (3 puffs of 4IU per nostril).	Placebo (Physiological Water(Sodium Chloride (NaCl) Solution)) n=17 Participants Administration via nasal spray Placebo (Physiological water (solution of sodium chloride (NaCl) in water)): Placebo nasal spray.
Change From Baseline in Brain Connectivity During Rest (Resting-state fMRI) After 8 Weeks, Including 4 Weeks Without Nasal Spray	-0.07 Change-from-base z-transformed r-value Standard Deviation 0.17	0.13 Change-from-base z-transformed r-value Standard Deviation 0.18

PRIMARY outcome

Timeframe: Value at 52 weeks minus value at baseline

Population: 1 subject lost in Syntocinon group due to subject withdrawal. (+ 3 additional participants lost for 1-year follow-up) 1 subject lost in Placebo group due to low data quality (excessive in-scanner head motion) (+ 3 additional participants lost for 1-year follow-up)

Change from baseline in brain connectivity during rest (resting-state fMRI) after 52 weeks, including 48 weeks without nasal spray Amygdala connectivity (Change-from-baseline z-transformed r-value) Higher z-transformed r-value indicates higher connectivity (higher correlated brain activity)

Outcome measures

Outcome measures
Measure	Syntocinon (Oxytocin, Product Code RVG 03716) n=18 Participants Administration via nasal spray Syntocinon (Oxytocin): Syntocinon nasal spray. A single dose (24IU) of nasal spray (3 puffs of 4IU per nostril).	Placebo (Physiological Water(Sodium Chloride (NaCl) Solution)) n=14 Participants Administration via nasal spray Placebo (Physiological water (solution of sodium chloride (NaCl) in water)): Placebo nasal spray.
Change From Baseline in Brain Connectivity During Rest (Resting-state fMRI) After 52 Weeks, Including 48 Weeks Without Nasal Spray	-0.06 Change-from-base z-transformed r-value Standard Deviation 0.20	0.11 Change-from-base z-transformed r-value Standard Deviation 0.23

SECONDARY outcome

Timeframe: Value at 30 minutes minus value at baseline

Population: 1 subject lost in Syntocinon group due to subject withdrawal. 1 subject lost in Placebo group due to low data quality (excessive in-scanner head motion)

Change from baseline in performance on the emotion recognition task (accuracy/reaction time) after a single dose of nasal spray Emotion recognition from point-light displays conveying biological motion. Accuracy (acc) is measured in % of correct responses. Reaction time (rt) is measured in milliseconds. Higher (accuracy/ reaction time) ratio indicates better performance.

Outcome measures

Outcome measures
Measure	Syntocinon (Oxytocin, Product Code RVG 03716) n=21 Participants Administration via nasal spray Syntocinon (Oxytocin): Syntocinon nasal spray. A single dose (24IU) of nasal spray (3 puffs of 4IU per nostril).	Placebo (Physiological Water(Sodium Chloride (NaCl) Solution)) n=17 Participants Administration via nasal spray Placebo (Physiological water (solution of sodium chloride (NaCl) in water)): Placebo nasal spray.
Change From Baseline in Performance on the Emotion Recognition Task (Accuracy/Reaction Time) After a Single Dose of Nasal Spray	0.000029 Change in performance (acc/rt ratio) Standard Deviation 0.000069	0.000065 Change in performance (acc/rt ratio) Standard Deviation 0.000071

SECONDARY outcome

Timeframe: Value at 4 weeks minus value at baseline

Population: 1 subject lost in Syntocinon group due to subject withdrawal. 1 subject lost in Placebo group due to low data quality (excessive in-scanner head motion)

Change from baseline in performance on the emotion recognition task (accuracy/ reaction time) after 4 weeks of nasal spray. Emotion recognition from point-light displays conveying biological motion. Accuracy (acc) is measured in % of correct responses. Reaction time (rt) is measured in milliseconds. Higher (accuracy/ reaction time) ratio indicates better performance.

Outcome measures

Outcome measures
Measure	Syntocinon (Oxytocin, Product Code RVG 03716) n=21 Participants Administration via nasal spray Syntocinon (Oxytocin): Syntocinon nasal spray. A single dose (24IU) of nasal spray (3 puffs of 4IU per nostril).	Placebo (Physiological Water(Sodium Chloride (NaCl) Solution)) n=17 Participants Administration via nasal spray Placebo (Physiological water (solution of sodium chloride (NaCl) in water)): Placebo nasal spray.
Change From Baseline in Performance on the Emotion Recognition Task (Accuracy/ Reaction Time) After 4 Weeks of Nasal Spray	0.000044 Change in performance (acc/rt ratio) Standard Deviation 0.000079	0.000073 Change in performance (acc/rt ratio) Standard Deviation 0.000071

SECONDARY outcome

Timeframe: Value at 8 weeks minus value at baseline

Population: 1 subject lost in Syntocinon group due to subject withdrawal. 1 subject lost in Placebo group due to low data quality (excessive in-scanner head motion)

Change from baseline in performance on the emotion recognition task (accuracy/ reaction time) after 8 weeks (including 4 weeks without nasal spray). Emotion recognition from point-light displays conveying biological motion. Accuracy (acc) is measured in % of correct responses. Reaction time (rt) is measured in milliseconds. Higher (accuracy/ reaction time) ratio indicates better performance.

Outcome measures

Outcome measures
Measure	Syntocinon (Oxytocin, Product Code RVG 03716) n=21 Participants Administration via nasal spray Syntocinon (Oxytocin): Syntocinon nasal spray. A single dose (24IU) of nasal spray (3 puffs of 4IU per nostril).	Placebo (Physiological Water(Sodium Chloride (NaCl) Solution)) n=17 Participants Administration via nasal spray Placebo (Physiological water (solution of sodium chloride (NaCl) in water)): Placebo nasal spray.
Change From Baseline in Performance on the Emotion Recognition Task (Accuracy/ Reaction Time) After 8 Weeks (Including 4 Weeks Without Nasal Spray)	0.000070 Change in performance (acc/rt ratio) Standard Deviation 0.000084	0.000088 Change in performance (acc/rt ratio) Standard Deviation 0.000089

SECONDARY outcome

Timeframe: Value at 52 weeks minus value at baseline

Population: 1 subject lost in Syntocinon group due to subject withdrawal. (+ 3 additional participants lost for 1-year follow-up) 1 subject lost in Placebo group due to low data quality (excessive in-scanner head motion) (+ 3 additional participants lost for 1-year follow-up)

Change from baseline in performance on the emotion recognition task (accuracy/ reaction time) after 52 weeks (including 48 weeks without nasal spray) Accuracy (acc) is measured in % of correct responses. Reaction time (rt) is measured in milliseconds. Higher (accuracy/ reaction time) ratio indicates better performance.

Outcome measures

Outcome measures
Measure	Syntocinon (Oxytocin, Product Code RVG 03716) n=18 Participants Administration via nasal spray Syntocinon (Oxytocin): Syntocinon nasal spray. A single dose (24IU) of nasal spray (3 puffs of 4IU per nostril).	Placebo (Physiological Water(Sodium Chloride (NaCl) Solution)) n=14 Participants Administration via nasal spray Placebo (Physiological water (solution of sodium chloride (NaCl) in water)): Placebo nasal spray.
Change From Baseline in Performance on the Emotion Recognition Task (Accuracy/ Reaction Time) After 52 Weeks (Including 48 Weeks Without Nasal Spray)	0.000071 Change in performance (acc/rt ratio) Standard Deviation 0.000079	0.000084 Change in performance (acc/rt ratio) Standard Deviation 0.000094

SECONDARY outcome

Timeframe: Value at 4 weeks minus value at baseline

Population: Intention-to-treat Syntocinon: IPPA Mother, IPPA Father (n= 21) (listwise missing data: n= 1) SRS-A informant (n= 17) (missing baseline data: n= 5) Placebo: RBS-R, WHO-QOL (n= 17) (missing baseline data n= 1) SRS-A informant (n= 15) (missing baseline data: n= 3)

The Social Responsiveness Scale (for adults) (SRS-A) uses a four-point Likert-scale. Higher scores indicate lower social responsiveness. The Repetitive Behavior Scale - Revised (RBS-R) uses a four-point Likert-scale. Higher scores indicate a higher frequency and/or higher severity of restricted and repetitive behaviors. The State Adult Attachment Measure (SAAM) uses a seven-point Likert-scale.Higher scores indicate lower perceived secure attachment on the attachment avoidance and attachment anxiety subscales, and higher perceived secure attachment on the attachment security subscale. Inventory of Parent and Peer Attachment (IPPA) uses a four-point Likert-scale. Higher scores indicate indicate increased feelings of secure attachment towards peers or parents. World Health Organization Quality of Life - Bref (WHO-QL) uses a five-point Likert scale. Higher scores indicate better quality of life. Profile of Mood States (POMS). five-point Likert scale.

Outcome measures

SECONDARY outcome

Timeframe: Value at 8 weeks minus value at baseline

Population: Intention-to-treat Syntocinon: IPPA Mother, IPPA Father (n= 21) (listwise missing data: n= 1) SRS-A informant (n= 17) (missing baseline data: n= 5) Placebo: RBS-R, WHO-QOL (n= 17) (missing baseline data n= 1) SRS-A informant (n= 15) (missing baseline data: n= 3)

The Social Responsiveness Scale (for adults) (SRS-A) uses a four-point Likert-scale. Higher scores indicate lower social responsiveness. The Repetitive Behavior Scale - Revised (RBS-R) uses a four-point Likert-scale. Higher scores indicate a higher frequency and/or higher severity of restricted and repetitive behaviors. The State Adult Attachment Measure (SAAM) uses a seven-point Likert-scale.Higher scores indicate lower perceived secure attachment on the attachment avoidance and attachment anxiety subscales, and higher perceived secure attachment on the attachment security subscale. Inventory of Parent and Peer Attachment (IPPA) uses a four-point Likert-scale. Higher scores indicate indicate increased feelings of secure attachment towards peers or parents. World Health Organization Quality of Life - Bref (WHO-QL) uses a five-point Likert scale. Higher scores indicate better quality of life. Profile of Mood States (POMS). five-point Likert scale.

Outcome measures

SECONDARY outcome

Timeframe: Value at 52 weeks minus value at baseline

Population: Intention-to-treat Syntocinon: IPPA Mother, IPPA Father (n= 21) (listwise missing data: n= 1) SRS-A informant (n= 17) (missing baseline data: n= 5) Placebo: RBS-R, WHO-QOL (n= 17) (missing baseline data n= 1) SRS-A informant (n= 15) (missing baseline data: n= 3)

The Social Responsiveness Scale (for adults) (SRS-A) uses a four-point Likert-scale. Higher scores indicate lower social responsiveness. The Repetitive Behavior Scale - Revised (RBS-R) uses a four-point Likert-scale. Higher scores indicate a higher frequency and/or higher severity of restricted and repetitive behaviors. The State Adult Attachment Measure (SAAM) uses a seven-point Likert-scale.Higher scores indicate lower perceived secure attachment on the attachment avoidance and attachment anxiety subscales, and higher perceived secure attachment on the attachment security subscale. Inventory of Parent and Peer Attachment (IPPA) uses a four-point Likert-scale. Higher scores indicate indicate increased feelings of secure attachment towards peers or parents. World Health Organization Quality of Life - Bref (WHO-QOL) uses a five-point Likert scale. Higher scores indicate better quality of life. Profile of Mood States (POMS). five-point Likert scale.

Outcome measures

SECONDARY outcome

Timeframe: Value at 30 minutes minus value at baseline

Change from baseline in scores on one questionnaire assessing mood (Profile of Mood States - POMS) after a single dose of nasal spray. This instrument comprises emotional adjectives subdivided in five domains: tension (6 items). depression (8 items). vigor (5 items). fatigue (6 items) and anger (7 items) which have to be rated on a five-point Likert scale ranging from 0 (not at all), 1 (a little), 2 (moderately), 3 (quite a lot), to 4 (extremely). Only for the vigor scale, higher scores indicate improvement.

Outcome measures

Outcome measures
Measure	Syntocinon (Oxytocin, Product Code RVG 03716) n=22 Participants Administration via nasal spray Syntocinon (Oxytocin): Syntocinon nasal spray. A single dose (24IU) of nasal spray (3 puffs of 4IU per nostril).	Placebo (Physiological Water(Sodium Chloride (NaCl) Solution)) n=18 Participants Administration via nasal spray Placebo (Physiological water (solution of sodium chloride (NaCl) in water)): Placebo nasal spray.
Change From Baseline in Scores on Questionnaire Assessing Mood After a Single Dose of Nasal Spray POMS - Tension	-1.59 Change from base (units on a scale) Standard Deviation 2.11	-1.39 Change from base (units on a scale) Standard Deviation 2.15
Change From Baseline in Scores on Questionnaire Assessing Mood After a Single Dose of Nasal Spray POMS - Anger	-0.09 Change from base (units on a scale) Standard Deviation 2.39	-0.28 Change from base (units on a scale) Standard Deviation 0.89
Change From Baseline in Scores on Questionnaire Assessing Mood After a Single Dose of Nasal Spray POMS - Depression	-0.23 Change from base (units on a scale) Standard Deviation 1.45	-0.67 Change from base (units on a scale) Standard Deviation 2.25
Change From Baseline in Scores on Questionnaire Assessing Mood After a Single Dose of Nasal Spray POMS - Vigor	0.27 Change from base (units on a scale) Standard Deviation 2.37	-0.50 Change from base (units on a scale) Standard Deviation 2.38
Change From Baseline in Scores on Questionnaire Assessing Mood After a Single Dose of Nasal Spray POMS - Fatigue	-1.00 Change from base (units on a scale) Standard Deviation 2.41	-0.72 Change from base (units on a scale) Standard Deviation 3.68

Adverse Events

Syntocinon (Oxytocin, Product Code RVG 03716)

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Placebo (Physiological Water(Sodium Chloride (NaCl) Solution))

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Syntocinon (Oxytocin, Product Code RVG 03716) n=22 participants at risk Administration via nasal spray Syntocinon (Oxytocin): Syntocinon nasal spray. A single dose (24IU) of nasal spray (3 puffs of 4IU per nostril), followed by 4 weeks of a daily single dose (24IU; 3 puffs of 4IU per nostril) of nasal spray	Placebo (Physiological Water(Sodium Chloride (NaCl) Solution)) n=18 participants at risk Administration via nasal spray Placebo (Physiological water (solution of sodium chloride (NaCl) in water)): Placebo nasal spray. A single dose (24IU) of nasal spray (3 puffs of 4IU per nostril), followed by 4 weeks of a daily single dose (24IU; 3 puffs of 4IU per nostril) of nasal spray
Respiratory, thoracic and mediastinal disorders Nasal irritation/ runny nose	9.1% 2/22 • Number of events 2 • Adverse event data were collected over a period of (approximately) four weeks. Adverse event data were collected via weekly journal entries. In the journal we provided an extensive list of potential adverse events and a blank space below the list to write down adverse events not mentioned in the list. Participants were asked to indicate whether or not they had experienced the event, when it started, how long it lasted, and the severity of the adverse event (mild, moderate, severe).	16.7% 3/18 • Number of events 3 • Adverse event data were collected over a period of (approximately) four weeks. Adverse event data were collected via weekly journal entries. In the journal we provided an extensive list of potential adverse events and a blank space below the list to write down adverse events not mentioned in the list. Participants were asked to indicate whether or not they had experienced the event, when it started, how long it lasted, and the severity of the adverse event (mild, moderate, severe).

Additional Information

Prof. Dr. Kaat Alaerts

KU Leuven

Phone: 16 37 64 46

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Syntocinon (Oxytocin, Product Code RVG 03716) n=22 Participants Administration via nasal spray Syntocinon (Oxytocin): Syntocinon nasal spray. A single dose (24IU) of nasal spray (3 puffs of 4IU per nostril).	Placebo (Physiological Water(Sodium Chloride (NaCl) Solution)) n=18 Participants Administration via nasal spray Placebo (Physiological water (solution of sodium chloride (NaCl) in water)): Placebo nasal spray.
Change From Baseline in Informant-based/ Self-report Scores on Questionnaires Assessing Attachment, Social Functioning, Quality of Life and Mood After 4 Weeks of Nasal Spray SRS-A informant-based	0.0 Change from base (units on a scale) Standard Deviation 15.86	-0.87 Change from base (units on a scale) Standard Deviation 12.83
Change From Baseline in Informant-based/ Self-report Scores on Questionnaires Assessing Attachment, Social Functioning, Quality of Life and Mood After 4 Weeks of Nasal Spray RBS-R	-4.77 Change from base (units on a scale) Standard Deviation 6.47	-1.76 Change from base (units on a scale) Standard Deviation 4.75
Change From Baseline in Informant-based/ Self-report Scores on Questionnaires Assessing Attachment, Social Functioning, Quality of Life and Mood After 4 Weeks of Nasal Spray SAAM avoidance	-0.40 Change from base (units on a scale) Standard Deviation 0.71	0.06 Change from base (units on a scale) Standard Deviation 0.98
Change From Baseline in Informant-based/ Self-report Scores on Questionnaires Assessing Attachment, Social Functioning, Quality of Life and Mood After 4 Weeks of Nasal Spray SAAM security	0.27 Change from base (units on a scale) Standard Deviation 0.77	0.05 Change from base (units on a scale) Standard Deviation 0.66
Change From Baseline in Informant-based/ Self-report Scores on Questionnaires Assessing Attachment, Social Functioning, Quality of Life and Mood After 4 Weeks of Nasal Spray IPPA Peers	1.45 Change from base (units on a scale) Standard Deviation 3.85	0.56 Change from base (units on a scale) Standard Deviation 4.05
Change From Baseline in Informant-based/ Self-report Scores on Questionnaires Assessing Attachment, Social Functioning, Quality of Life and Mood After 4 Weeks of Nasal Spray IPPA Mother	-0.52 Change from base (units on a scale) Standard Deviation 2.71	0.44 Change from base (units on a scale) Standard Deviation 3.45
Change From Baseline in Informant-based/ Self-report Scores on Questionnaires Assessing Attachment, Social Functioning, Quality of Life and Mood After 4 Weeks of Nasal Spray IPPA Father	0.43 Change from base (units on a scale) Standard Deviation 3.30	-0.61 Change from base (units on a scale) Standard Deviation 3.81
Change From Baseline in Informant-based/ Self-report Scores on Questionnaires Assessing Attachment, Social Functioning, Quality of Life and Mood After 4 Weeks of Nasal Spray WHO-QOL	1.77 Change from base (units on a scale) Standard Deviation 8.04	-1.35 Change from base (units on a scale) Standard Deviation 6.74
Change From Baseline in Informant-based/ Self-report Scores on Questionnaires Assessing Attachment, Social Functioning, Quality of Life and Mood After 4 Weeks of Nasal Spray POMS - Tension	-2.00 Change from base (units on a scale) Standard Deviation 2.29	-2.39 Change from base (units on a scale) Standard Deviation 3.03
Change From Baseline in Informant-based/ Self-report Scores on Questionnaires Assessing Attachment, Social Functioning, Quality of Life and Mood After 4 Weeks of Nasal Spray POMS - Anger	0.00 Change from base (units on a scale) Standard Deviation 4.05	-0.61 Change from base (units on a scale) Standard Deviation 2.73
Change From Baseline in Informant-based/ Self-report Scores on Questionnaires Assessing Attachment, Social Functioning, Quality of Life and Mood After 4 Weeks of Nasal Spray POMS - Depression	-1.14 Change from base (units on a scale) Standard Deviation 4.50	-0.33 Change from base (units on a scale) Standard Deviation 2.81
Change From Baseline in Informant-based/ Self-report Scores on Questionnaires Assessing Attachment, Social Functioning, Quality of Life and Mood After 4 Weeks of Nasal Spray POMS - Vigor	-1.00 Change from base (units on a scale) Standard Deviation 2.53	-2.94 Change from base (units on a scale) Standard Deviation 3.64
Change From Baseline in Informant-based/ Self-report Scores on Questionnaires Assessing Attachment, Social Functioning, Quality of Life and Mood After 4 Weeks of Nasal Spray POMS - Fatigue	-2.09 Change from base (units on a scale) Standard Deviation 3.99	-1.11 Change from base (units on a scale) Standard Deviation 5.12
Change From Baseline in Informant-based/ Self-report Scores on Questionnaires Assessing Attachment, Social Functioning, Quality of Life and Mood After 4 Weeks of Nasal Spray SRS-A self-report	-5.55 Change from base (units on a scale) Standard Deviation 11.40	-1.06 Change from base (units on a scale) Standard Deviation 10.01
Change From Baseline in Informant-based/ Self-report Scores on Questionnaires Assessing Attachment, Social Functioning, Quality of Life and Mood After 4 Weeks of Nasal Spray SAAM anxiety	-0.14 Change from base (units on a scale) Standard Deviation 0.75	0.28 Change from base (units on a scale) Standard Deviation 0.95

Measure	Syntocinon (Oxytocin, Product Code RVG 03716) n=22 Participants Administration via nasal spray Syntocinon (Oxytocin): Syntocinon nasal spray. A single dose (24IU) of nasal spray (3 puffs of 4IU per nostril).	Placebo (Physiological Water(Sodium Chloride (NaCl) Solution)) n=18 Participants Administration via nasal spray Placebo (Physiological water (solution of sodium chloride (NaCl) in water)): Placebo nasal spray.
Change From Baseline in Informant-based/ Self-report Scores on Questionnaires Assessing Attachment, Social Functioning, Quality of Life and Mood After 8 Weeks, Including 4 Weeks Without Nasal Spray SRS-A self-report	-5.64 Change from base (units on a scale) Standard Deviation 12.57	-7.67 Change from base (units on a scale) Standard Deviation 12.09
Change From Baseline in Informant-based/ Self-report Scores on Questionnaires Assessing Attachment, Social Functioning, Quality of Life and Mood After 8 Weeks, Including 4 Weeks Without Nasal Spray SRS-A informant-based	-9.59 Change from base (units on a scale) Standard Deviation 10.98	-1.20 Change from base (units on a scale) Standard Deviation 10.73
Change From Baseline in Informant-based/ Self-report Scores on Questionnaires Assessing Attachment, Social Functioning, Quality of Life and Mood After 8 Weeks, Including 4 Weeks Without Nasal Spray RBS-R	-4.91 Change from base (units on a scale) Standard Deviation 6.33	-2.35 Change from base (units on a scale) Standard Deviation 3.43
Change From Baseline in Informant-based/ Self-report Scores on Questionnaires Assessing Attachment, Social Functioning, Quality of Life and Mood After 8 Weeks, Including 4 Weeks Without Nasal Spray SAAM avoidance	-0.38 Change from base (units on a scale) Standard Deviation 0.70	-0.06 Change from base (units on a scale) Standard Deviation 0.76
Change From Baseline in Informant-based/ Self-report Scores on Questionnaires Assessing Attachment, Social Functioning, Quality of Life and Mood After 8 Weeks, Including 4 Weeks Without Nasal Spray SAAM security	0.04 Change from base (units on a scale) Standard Deviation 1.01	-0.40 Change from base (units on a scale) Standard Deviation 0.99
Change From Baseline in Informant-based/ Self-report Scores on Questionnaires Assessing Attachment, Social Functioning, Quality of Life and Mood After 8 Weeks, Including 4 Weeks Without Nasal Spray SAAM anxiety	0.08 Change from base (units on a scale) Standard Deviation 1.05	0.11 Change from base (units on a scale) Standard Deviation 0.87
Change From Baseline in Informant-based/ Self-report Scores on Questionnaires Assessing Attachment, Social Functioning, Quality of Life and Mood After 8 Weeks, Including 4 Weeks Without Nasal Spray IPPA Peers	1.32 Change from base (units on a scale) Standard Deviation 3.71	0.06 Change from base (units on a scale) Standard Deviation 3.70
Change From Baseline in Informant-based/ Self-report Scores on Questionnaires Assessing Attachment, Social Functioning, Quality of Life and Mood After 8 Weeks, Including 4 Weeks Without Nasal Spray IPPA Mother	-0.38 Change from base (units on a scale) Standard Deviation 3.43	0.06 Change from base (units on a scale) Standard Deviation 4.35
Change From Baseline in Informant-based/ Self-report Scores on Questionnaires Assessing Attachment, Social Functioning, Quality of Life and Mood After 8 Weeks, Including 4 Weeks Without Nasal Spray IPPA Father	0.52 Change from base (units on a scale) Standard Deviation 3.59	-0.33 Change from base (units on a scale) Standard Deviation 3.87
Change From Baseline in Informant-based/ Self-report Scores on Questionnaires Assessing Attachment, Social Functioning, Quality of Life and Mood After 8 Weeks, Including 4 Weeks Without Nasal Spray WHO-QOL	1.14 Change from base (units on a scale) Standard Deviation 5.48	0.35 Change from base (units on a scale) Standard Deviation 4.53
Change From Baseline in Informant-based/ Self-report Scores on Questionnaires Assessing Attachment, Social Functioning, Quality of Life and Mood After 8 Weeks, Including 4 Weeks Without Nasal Spray POMS - Tension	-2.64 Change from base (units on a scale) Standard Deviation 2.80	-2.11 Change from base (units on a scale) Standard Deviation 3.22
Change From Baseline in Informant-based/ Self-report Scores on Questionnaires Assessing Attachment, Social Functioning, Quality of Life and Mood After 8 Weeks, Including 4 Weeks Without Nasal Spray POMS - Anger	0.36 Change from base (units on a scale) Standard Deviation 3.68	-0.39 Change from base (units on a scale) Standard Deviation 3.91
Change From Baseline in Informant-based/ Self-report Scores on Questionnaires Assessing Attachment, Social Functioning, Quality of Life and Mood After 8 Weeks, Including 4 Weeks Without Nasal Spray POMS - Depression	-0.82 Change from base (units on a scale) Standard Deviation 2.63	0.22 Change from base (units on a scale) Standard Deviation 3.41
Change From Baseline in Informant-based/ Self-report Scores on Questionnaires Assessing Attachment, Social Functioning, Quality of Life and Mood After 8 Weeks, Including 4 Weeks Without Nasal Spray POMS - Vigor	0.14 Change from base (units on a scale) Standard Deviation 3.58	-1.44 Change from base (units on a scale) Standard Deviation 4.33
Change From Baseline in Informant-based/ Self-report Scores on Questionnaires Assessing Attachment, Social Functioning, Quality of Life and Mood After 8 Weeks, Including 4 Weeks Without Nasal Spray POMS - Fatigue	-2.69 Change from base (units on a scale) Standard Deviation 2.71	-2.33 Change from base (units on a scale) Standard Deviation 4.47

Measure	Syntocinon (Oxytocin, Product Code RVG 03716) n=22 Participants Administration via nasal spray Syntocinon (Oxytocin): Syntocinon nasal spray. A single dose (24IU) of nasal spray (3 puffs of 4IU per nostril).	Placebo (Physiological Water(Sodium Chloride (NaCl) Solution)) n=18 Participants Administration via nasal spray Placebo (Physiological water (solution of sodium chloride (NaCl) in water)): Placebo nasal spray.
Change From Baseline in Informant-based/ Self-report Scores on Questionnaires Assessing Attachment, Social Functioning, Quality of Life and Mood After 52 Weeks, Including 48 Weeks Without Nasal Spray RBS-R	-4.91 Change from base (units on a scale) Standard Deviation 9.46	-0.41 Change from base (units on a scale) Standard Deviation 4.27
Change From Baseline in Informant-based/ Self-report Scores on Questionnaires Assessing Attachment, Social Functioning, Quality of Life and Mood After 52 Weeks, Including 48 Weeks Without Nasal Spray IPPA Peers	0.68 Change from base (units on a scale) Standard Deviation 6.26	1.28 Change from base (units on a scale) Standard Deviation 4.17
Change From Baseline in Informant-based/ Self-report Scores on Questionnaires Assessing Attachment, Social Functioning, Quality of Life and Mood After 52 Weeks, Including 48 Weeks Without Nasal Spray IPPA Mother	0.33 Change from base (units on a scale) Standard Deviation 3.91	1.50 Change from base (units on a scale) Standard Deviation 5.44
Change From Baseline in Informant-based/ Self-report Scores on Questionnaires Assessing Attachment, Social Functioning, Quality of Life and Mood After 52 Weeks, Including 48 Weeks Without Nasal Spray WHO-QOL	1.14 Change from base (units on a scale) Standard Deviation 8.37	0.29 Change from base (units on a scale) Standard Deviation 4.21
Change From Baseline in Informant-based/ Self-report Scores on Questionnaires Assessing Attachment, Social Functioning, Quality of Life and Mood After 52 Weeks, Including 48 Weeks Without Nasal Spray POMS - Tension	-1.86 Change from base (units on a scale) Standard Deviation 2.29	-2.28 Change from base (units on a scale) Standard Deviation 3.46
Change From Baseline in Informant-based/ Self-report Scores on Questionnaires Assessing Attachment, Social Functioning, Quality of Life and Mood After 52 Weeks, Including 48 Weeks Without Nasal Spray POMS - Anger	0.59 Change from base (units on a scale) Standard Deviation 3.69	0.06 Change from base (units on a scale) Standard Deviation 3.84
Change From Baseline in Informant-based/ Self-report Scores on Questionnaires Assessing Attachment, Social Functioning, Quality of Life and Mood After 52 Weeks, Including 48 Weeks Without Nasal Spray SRS-A self-report	-8.59 Change from base (units on a scale) Standard Deviation 20.95	-6.72 Change from base (units on a scale) Standard Deviation 21.01
Change From Baseline in Informant-based/ Self-report Scores on Questionnaires Assessing Attachment, Social Functioning, Quality of Life and Mood After 52 Weeks, Including 48 Weeks Without Nasal Spray SRS-A informant-based	-7.41 Change from base (units on a scale) Standard Deviation 19.26	-4.13 Change from base (units on a scale) Standard Deviation 24.64
Change From Baseline in Informant-based/ Self-report Scores on Questionnaires Assessing Attachment, Social Functioning, Quality of Life and Mood After 52 Weeks, Including 48 Weeks Without Nasal Spray SAAM avoidance	-0.52 Change from base (units on a scale) Standard Deviation 1.18	0.0 Change from base (units on a scale) Standard Deviation 0.75
Change From Baseline in Informant-based/ Self-report Scores on Questionnaires Assessing Attachment, Social Functioning, Quality of Life and Mood After 52 Weeks, Including 48 Weeks Without Nasal Spray SAAM security	0.20 Change from base (units on a scale) Standard Deviation 1.52	-0.14 Change from base (units on a scale) Standard Deviation 0.66
Change From Baseline in Informant-based/ Self-report Scores on Questionnaires Assessing Attachment, Social Functioning, Quality of Life and Mood After 52 Weeks, Including 48 Weeks Without Nasal Spray SAAM anxiety	0.17 Change from base (units on a scale) Standard Deviation 0.94	0.11 Change from base (units on a scale) Standard Deviation 1.21
Change From Baseline in Informant-based/ Self-report Scores on Questionnaires Assessing Attachment, Social Functioning, Quality of Life and Mood After 52 Weeks, Including 48 Weeks Without Nasal Spray IPPA Father	0.57 Change from base (units on a scale) Standard Deviation 4.08	-0.50 Change from base (units on a scale) Standard Deviation 4.53
Change From Baseline in Informant-based/ Self-report Scores on Questionnaires Assessing Attachment, Social Functioning, Quality of Life and Mood After 52 Weeks, Including 48 Weeks Without Nasal Spray POMS - Depression	0.50 Change from base (units on a scale) Standard Deviation 2.63	-0.28 Change from base (units on a scale) Standard Deviation 3.51
Change From Baseline in Informant-based/ Self-report Scores on Questionnaires Assessing Attachment, Social Functioning, Quality of Life and Mood After 52 Weeks, Including 48 Weeks Without Nasal Spray POMS - Vigor	1.14 Change from base (units on a scale) Standard Deviation 3.88	-0.61 Change from base (units on a scale) Standard Deviation 3.27
Change From Baseline in Informant-based/ Self-report Scores on Questionnaires Assessing Attachment, Social Functioning, Quality of Life and Mood After 52 Weeks, Including 48 Weeks Without Nasal Spray POMS - Fatigue	-0.23 Change from base (units on a scale) Standard Deviation 6.04	0.39 Change from base (units on a scale) Standard Deviation 4.73