A Phase 2 interventional study of Oxytocin nasal spray and Placebo in Autism, sponsored by Stanford University. Completed at 1 site in United States. Open to participants aged 6 Years to 12 Years. Per ClinicalTrials.gov, last updated 2019-07-15.
Sponsored by Stanford University · Phase 2, Interventional, and Treatment
Autism is a pervasive developmental disorder characterized by core deficits in social behavior and communication, and the presence of repetitive or stereotyped behaviors. It is one of three recognized disorders in the autism spectrum which affects an estimated 1 in 88 children in the United States. At present, pharmacotherapies target only associated features of autism, with no effective drug treatments for the social impairments. Several lines of evidence now suggest that the neuropeptide oxytocin (OT) may be an effective treatment for the core social deficits in autism. Here we will test the effects of twice daily intranasal OT (24 IU) over a 4-week period for enhancing social deficits in male and female children aged 6-12 years with autism. This research has high potential to lead to the development of more effective treatments and earlier interventions for children with autism.
In recent years, the neuropeptide oxytocin (OT) has been implicated in a wide range of social behaviors including attachment bonds, emotion recognition, eye gaze to social cues, and memory for social information. Social impairments represent one of the most intractable features of autism, and evidence now suggests that OT biology is dysregulated in individuals with this disorder. The central aim of the research outlined here is to test whether OT administration to children with autism increases their quality and quantity of social interactions and enhances their ability to process emotional and social information. Findings from initial single-dose OT administration studies in teenaged and adult males with autism have shown improvement in some aspects of social functioning, but replication and extension to well-controlled treatment trials with younger male and female subjects is necessary to evaluate effectiveness. We therefore aim to investigate the effect of intranasal OT on social cognition and behavior immediately following a single-dose (24IU) and following a 4-week period of OT (24IU BID) administration in a sample of 50 subjects with autism aged 6 to 12 years. The primary outcome for this study is change in social behavior, as determined by parent ratings on the Social Responsiveness Scale (SRS) after the 4-week treatment period. Secondary outcomes are changes in functioning on laboratory-based measures of social behavior and cognition following single-dose and 4-week OT administration. Research in a small study sample (N=13) also identified treatment responders and non-responders to a single-dose of OT. Thus, we also aim to identify biological and cognitive and behavioral variables (i.e., pretreatment levels of social functioning and pretreatment plasma hormone levels) that may influence treatment response efficacy in our larger study sample. On completion of the 4-week treatment period all subjects will have the option of participating in another 4-week double-blind trial in which they will be switched to the alternate nasal spray to that which they previously received. They will then undergo a fourth and final assessment time-point using the same testing procedures as outlined above on completion of the 4-week dosing. By providing subjects with the option of participating in a second 4-week treatment trial, all subjects will have an opportunity to receive the active oxytocin nasal spray. We also will be able to examine any ongoing effects of oxytocin treatment in the group receiving placebo during the second 4-week administration period. Subjects not willing to take part in the second trial will exit the study and will be referred to their treating physician.
1,344 studies on the registry are indexed under Autistic Disorder; 334 are open to participants now.
This study's enrollment of 54 is above the median of 45 across 1,044 interventional studies indexed under Autistic Disorder.
Browse Autistic Disorder studies →Stanford University is the lead sponsor of 2,117 studies on the registry; 425 are open to participants now.
Of its 259 completed or terminated interventional studies of FDA-regulated products, 197 (76%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Prior to randomization, all subjects will participate in a 1-week open-label placebo lead-in trial. Each subject will be administered the placebo nasal spray at Stanford University and then their parent will continue administering the nasal spray to the subject for 1 week at home. Each subject will then be randomly assigned either to the active group or to the placebo (stratified by gender) and will be given the appropriate nasal spray bottle and their parents will be responsible for administering 3 puffs per nostril (4 IU/puff) to their child for a total dose of 24 IU oxytocin or placebo twice daily (BID; morning and evening) for 4-weeks. On completion of this 4-week treatment trial subjects will have the option of participating in a second double-blind trial in which they will be assigned to the alternate nasal spray, to that which they received during the first 4-week trial, for an additional 4-week period.
Drug: Oxytocin nasal spray
The placebo nasal spray bottles will be prepared by adding all of the ingredients used in the Syntocinon nasal sprays with the exception of the concentrated oxytocin solution.
Drug: Placebo
24IU BID (3 x 0.1 mL \[4IU\] sprays per nostril twice daily for 4-weeks.
Also known as: Syntocinon® Nasal Spray
3 x 0.1 mL sprays per nostril twice daily for 4-weeks.
Change From Baseline in Parent Rated Social Responsiveness Scale (SRS) Scores During Treatment.
Social Responsiveness Scale (SRS) raw scores measure social abilities with lower raw scores meaning better social abilities. (Raw Score Range: 0 - 195)
Time frame: Baseline; Week 4
Number of Participants With Side Effects Assessed Using Parent Rated Dosage Record Treatment Emergent Symptom Scale (DOTES) Scores During Treatment
Dosage Record Treatment Emergent Symptom Scale (DOTES) side effects reported by parents during 4-weeks of treatment. Participant Counts are used.
Time frame: Baseline through Week 4
Change From Baseline in Height.
Time frame: Baseline; Week 4
Clinical Global Impression-Improvement (CGI-I) Score at Week 4
This outcome is reported as the count of participants in each CGI-I rating category at the week 4 visit, assessing change over the 4-week period. CGI-I rating of 1=Very Much Improved, 2=Much Improved, 3=Minimally Improved, 4=No Change, 5=Minimally Worse, 6=Much Worse, and 7=Very Much Worse.
Time frame: Baseline to Week 4
Parent Rated Aberrant Behavior Checklist (ABC) Irritability Scores at Baseline and Week 4
Higher scores indicate more symptoms, lower scores indicate fewer symptoms. Irritability scores can range from 0-45. Lethargy scores can range from 0-48. Stereotypy scores can range from 0-21. Hyperactivity scores can range from 0-48. Inappropriate speech scores can from 0-12.
Time frame: Baseline; Week 4
Change From Baseline in Parent Rated Spence Children's Anxiety Scale (SCAS) During Treatment.
Scale measuring severity of anxiety symptoms. Higher scores mean higher levels of anxiety, lower scores mean lower levels of anxiety. (Raw Score Range: 0 - 114)
Time frame: Baseline; Week 4
Change From Baseline in Vineland Adaptive Behavior Scales, Second Edition - Social and Communication Subscales During Treatment.
Higher Social Standard Score means better social skills, lower Social Standard Score means worse social skills. Higher Communication Standard Score means better communication skills, lower Communication Standard Score means worse communication skills. Standard Scores can range from 20 to 160.
Time frame: Baseline; Week 4
Change From Baseline in Laboratory Based Facial Emotion Recognition Abilities During Treatment.
Time frame: Up to 4 weeks
Change From Baseline in Laboratory Based Eye-gaze to Social Cues During Treatment.
Time frame: Baseline; Week 4
Change From Baseline in Reading the Mind in the Eyes Test, Child Version (RMET-child) Scores During Treatment.
Time frame: Up to 4 weeks
Change From Baseline in Laboratory Based Social Mimicry Abilities During Treatment.
Time frame: Up to 4 weeks
Change From Baseline in Developmental NEuroPSYchological Assessment (NEPSY-II) Affect Recognition Scores During Treatment.
Higher Affect Recognition scores mean better affect recognition abilities, lower Affect Recognition scores mean worse affect recognition abilities. Scores can range from 1 to 19.
Time frame: Baseline; Week 4
Change From Baseline in Plasma Oxytocin Levels During Treatment.
This outcome originally specified that oxytocin, vasopressin, and cortisol levels would be assessed; however, data on vasopressin and cortisol levels were not collected during the study. There are no clinical laboratory tests that establish a normative range for oxytocin. Measurements prior to and following treatment were intended to evaluate oxytocin level as a predictor of response.
Time frame: Up to 4 weeks
Change From Baseline in Parent Rated Repetitive Behavior Scale- Revised (RBS-R) Scores During Treatment.
Higher scores on the Repetitive Behavior Scale- Revised mean higher levels of repetitive and restricted behaviors. (Raw Score Total Range: 0 - 129)
Time frame: Baseline; Week 4
Change From Baseline in Weight
Time frame: Baseline; Week 4
Change From Baseline in Heart Rate
Time frame: Baseline; Week 4
Change From Baseline in Blood Pressure
Time frame: Baseline; Week 4
This study was conducted in the Autism and Developmental Disabilities Clinic in the Division of Child and Adolescent Psychiatry at Stanford University. Recruitment began in June 2012 and ended in April 2016. Participants were recruited through the Stanford Autism Research Registry, flyers posted in the community, posted online and special events.
| Milestone | Oxytocin Nasal Spray | Placebo Nasal Spray |
|---|---|---|
| Started | 16 | 18 |
| Completed | 14 | 18 |
| Not completed | 2 | 0 |
| Withdrew: Lost to follow-up | 1 | 0 |
| Withdrew: Withdrawal by subject | 1 | 0 |
Social Responsiveness Scale (SRS) raw scores measure social abilities with lower raw scores meaning better social abilities. (Raw Score Range: 0 - 195)
| units on a scale | Oxytocin Nasal Spray | Placebo Nasal Spray |
|---|---|---|
| Change From Baseline in Parent Rated Social Responsiveness Scale (SRS) Scores During Treatment. | 9.73 ± 2.64 | 3.18 ± 2.18 |
Dosage Record Treatment Emergent Symptom Scale (DOTES) side effects reported by parents during 4-weeks of treatment. Participant Counts are used.
| participants | Oxytocin Nasal Spray | Placebo Nasal Spray |
|---|---|---|
| Cold Symptoms | 0 | 1 |
| Fever | 0 | 1 |
| Cough | 1 | 0 |
| Headache | 1 | 0 |
| Insomnia | 1 | 1 |
| Excitement/Agitation | 1 | 2 |
| Depressive Affect | 0 | 1 |
| Labile Mood | 1 | 1 |
| Silly Behavior | 1 | 0 |
| More Distractible | 1 | 0 |
| Nasal Congestion | 3 | 0 |
| Epistaxis | 1 | 0 |
| Sneezing | 0 | 1 |
| Mouth Pain | 0 | 1 |
| Intranasal Swelling | 1 | 0 |
| Runny Nose | 1 | 0 |
| Blinking Eyes | 0 | 1 |
| Earache | 0 | 1 |
| Nasal Discomfort | 0 | 1 |
| Loose Stool | 1 | 0 |
| Constipation | 1 | 0 |
| Stomach Discomfort | 0 | 1 |
| Skin Cut | 0 | 2 |
| cm | Oxytocin Nasal Spray | Placebo Nasal Spray |
|---|---|---|
| Baseline | 134 (126 to 141) | 129 (122 to 135) |
| Week 4 | 134 (127 to 142) | 129 (122 to 136) |
This outcome is reported as the count of participants in each CGI-I rating category at the week 4 visit, assessing change over the 4-week period. CGI-I rating of 1=Very Much Improved, 2=Much Improved, 3=Minimally Improved, 4=No Change, 5=Minimally Worse, 6=Much Worse, and 7=Very Much Worse.
| Participants | Oxytocin Nasal Spray | Placebo Nasal Spray |
|---|---|---|
| Very Much Improved | 0 | 0 |
| Much Improved | 3 | 3 |
| Minimally Improved | 2 | 5 |
| No Change | 9 | 10 |
| Minimally Worse | 0 | 0 |
| Much Worse | 0 | 0 |
| Very Much Worse | 0 | 0 |
Higher scores indicate more symptoms, lower scores indicate fewer symptoms. Irritability scores can range from 0-45. Lethargy scores can range from 0-48. Stereotypy scores can range from 0-21. Hyperactivity scores can range from 0-48. Inappropriate speech scores can from 0-12.
| units on a scale | Oxytocin Nasal Spray | Placebo Nasal Spray |
|---|---|---|
| Baseline Irritablity | 13.20 ± 11.91 | 13.94 ± 8.71 |
| Week 4 Irritability | 8.86 ± 8.87 | 11.78 ± 8.11 |
| Baseline Lethargy | 14.13 ± 8.70 | 11.7 ± 8.34 |
| Week 4 Lethargy | 10.6 ± 4.07 | 7.33 ± 6.30 |
| Baseline Stereotypy | 5.69 ± 6.20 | 5.61 ± 4.55 |
| Week 4 Stereotypy | 4.86 ± 5.07 | 5.50 ± 4.85 |
| Baseline Hyperactivity | 15.00 ± 13.74 | 23.28 ± 10.74 |
| Week 4 Hyperactivity | 10.50 ± 10.17 | 19.11 ± 9.68 |
| Baseline Inappropriate Speech | 3.94 ± 3.28 | 5.44 ± 3.99 |
| Week 4 Inappropriate Speech | 2.86 ± 3.23 | 4.17 ± 3.31 |
Scale measuring severity of anxiety symptoms. Higher scores mean higher levels of anxiety, lower scores mean lower levels of anxiety. (Raw Score Range: 0 - 114)
| units on a scale | Oxytocin Nasal Spray | Placebo Nasal Spray |
|---|---|---|
| Change From Baseline in Parent Rated Spence Children's Anxiety Scale (SCAS) During Treatment. | 1.66 ± 3.05 | 4.53 ± 2.21 |
Higher Social Standard Score means better social skills, lower Social Standard Score means worse social skills. Higher Communication Standard Score means better communication skills, lower Communication Standard Score means worse communication skills. Standard Scores can range from 20 to 160.
| units on a scale | Oxytocin Nasal Spray | Placebo Nasal Spray |
|---|---|---|
| Baseline Social Standard Score | 61.4 ± 12.82 | 67.75 ± 12.45 |
| Week 4 Social Standard Score | 66.11 ± 16.03 | 70.92 ± 14.23 |
| Baseline Communication Standard Scores | 66.91 ± 19.60 | 71.80 ± 17.85 |
| Week 4 Communication Standard Scores | 71.33 ± 11.43 | 78.29 ± 19.12 |
No measurements were reported for this outcome.
No measurements were reported for this outcome.
No measurements were reported for this outcome.
No measurements were reported for this outcome.
Higher Affect Recognition scores mean better affect recognition abilities, lower Affect Recognition scores mean worse affect recognition abilities. Scores can range from 1 to 19.
| units on a scale | Oxytocin Nasal Spray | Placebo Nasal Spray |
|---|---|---|
| Baseline Affect Recognition Score | 10 ± 1.89 | 9.43 ± 3.78 |
| Week 4 Affect Recognition Score | 8.75 ± 1.5 | 6.43 ± 4.08 |
This outcome originally specified that oxytocin, vasopressin, and cortisol levels would be assessed; however, data on vasopressin and cortisol levels were not collected during the study. There are no clinical laboratory tests that establish a normative range for oxytocin. Measurements prior to and following treatment were intended to evaluate oxytocin level as a predictor of response.
| pg/mL | Oxytocin Nasal Spray | Placebo Nasal Spray |
|---|---|---|
| Baseline | 8.82 ± 4.67 | 8.66 ± 3.85 |
| Week 4 | 10.36 ± 3.57 | 8.40 ± 3.57 |
Higher scores on the Repetitive Behavior Scale- Revised mean higher levels of repetitive and restricted behaviors. (Raw Score Total Range: 0 - 129)
| units on a scale | Oxytocin Nasal Spray | Placebo Nasal Spray |
|---|---|---|
| Change From Baseline in Parent Rated Repetitive Behavior Scale- Revised (RBS-R) Scores During Treatment. | 5.68 ± 3.32 | 5.79 ± 2.78 |
| kilograms | Oxytocin Nasal Spray | Placebo Nasal Spray |
|---|---|---|
| Baseline | 32.7 (27.0 to 39.5) | 28.0 (23.5 to 33.2) |
| Week 4 | 33.5 (27.7 to 40.4) | 28.4 (23.9 to 33.7) |
| beats per minute | Oxytocin Nasal Spray | Placebo Nasal Spray |
|---|---|---|
| Baseline Sitting Heart Rate | 92.5 (83.0 to 101.9) | 92.7 (83.6 to 101.8) |
| Post 4 -Week Sitting Heart Rate | 97.1 (87.7 to 106.5) | 101.6 (92.5 to 110.6) |
| mmHg | Oxytocin Nasal Spray | Placebo Nasal Spray |
|---|---|---|
| Baseline Systolic Blood Pressure, Sitting | 104.2 (98.7 to 109.8) | 101.0 (95.6 to 106.4) |
| Post 4 -Week Systolic Blood Pressure, Sitting | 111.1 (105.5 to 116.6) | 110.9 (105.6 to 116.3) |
| Baseline Diastolic Blood Pressure, Sitting | 64.3 (59.0 to 69.6) | 64.6 (59.4 to 69.7) |
| Post 4 -Week Diastolic Blood Pressure, Sitting | 71.4 (66.1 to 76.7) | 68.9 (63.8 to 74.1) |
| Baseline Systolic Blood Pressure, Standing | 101.6 (95.2 to 108.1) | 107.7 (101.5 to 113.9) |
| Post 4 -Week Systolic Blood Pressure, Standing | 111.6 (105.2 to 118.1) | 105.6 (99.4 to 111.9) |
| Baseline Diastolic Blood Pressure, Standing | 63.3 (58.0 to 68.6) | 68.2 (63.1 to 73.3) |
| Post 4 -Week Diastolic Blood Pressure, Standing | 70.9 (65.6 to 76.2) | 69.8 (64.7 to 74.9) |
Collected over 4 weeks. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Oxytocin Nasal Spray | 0/14 (0%) | 0/14 (0%) | 11/14 (78.6%) |
| Placebo Nasal Spray | 0/18 (0%) | 0/18 (0%) | 12/18 (66.7%) |
| Event | Oxytocin Nasal Spray | Placebo Nasal Spray |
|---|---|---|
| Nasal CongestionGeneral disorders | 3/14 | 0/18 |
| Excitement/AgitationPsychiatric disorders | 1/14 | 2/18 |
| Skin CutSkin and subcutaneous tissue disorders | 0/14 | 2/18 |
| CoughGeneral disorders | 1/14 | 0/18 |
| HeadacheNervous system disorders | 1/14 | 0/18 |
| InsomniaPsychiatric disorders | 1/14 | 1/18 |
| Labile MoodPsychiatric disorders | 1/14 | 1/18 |
| Silly BehaviorPsychiatric disorders | 1/14 | 0/18 |
| More DistractiblePsychiatric disorders | 1/14 | 0/18 |
| EpistaxisGeneral disorders | 1/14 | 0/18 |
| Age, Categorical(Participants) | Oxytocin Nasal Spray | Placebo Nasal Spray | Total |
|---|---|---|---|
| <=18 years | 16 | 18 | 34 |
| Between 18 and 65 years | 0 | 0 | 0 |
| >=65 years | 0 | 0 | 0 |
| Sex: Female, Male(Participants) | Oxytocin Nasal Spray | Placebo Nasal Spray | Total |
|---|---|---|---|
| Female | 2 | 4 | 6 |
| Male | 14 | 14 | 28 |
| Race/Ethnicity, Customized(Participants) | Oxytocin Nasal Spray | Placebo Nasal Spray | Total |
|---|---|---|---|
| Caucasian | 6 | 8 | 14 |
| Asian | 4 | 5 | 9 |
| Other | 6 | 5 | 11 |
| Region of Enrollment(Participants) | Oxytocin Nasal Spray | Placebo Nasal Spray | Total |
|---|---|---|---|
| United States | 16 | 18 | 34 |
This study is completed, as verified in Jul 2019. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Stanford University