The Role of Vasopressin in the Social Deficits of Autism

• Sponsor: Stanford University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01962870
• Collaborator: National Institute of Mental Health (NIMH) (NIH)
• Enrollment: 68
• Location: 1
• Arms: 2
• Actual Duration (Months): 41.9
• Patients Per Site Per Month: 1.6

Study Details

Study Description

Brief Summary

Researchers at the Stanford University School of Medicine are seeking participants for a study examining the effectiveness of vasopressin, a neuropeptide, in treating children with autism spectrum disorder. Difficulty with social interactions is characteristic of people with autism, who often have problems interpreting facial expressions or maintaining eye contact while talking with someone. There are currently no effective medicines available to treat social problems in individuals with autism. Neuropeptides, such as vasopressin and oxytocin, are molecules used by neurons in the brain to communicate with one another. Vasopressin is closely related to oxytocin, which is currently being tested as a treatment for autism, and has been shown to enhance social functioning in animals. Animal studies have shown that when the proper functioning of vasopressin is experimentally altered, animals develop a variety of social deficits, including impaired memory for peers and a reduced interest in social interaction. Researchers found that when vasopressin was administered to mice with a genetically induced form of autism, their social functioning improved. Vasopressin is already approved by the Food and Drug Administration for use in humans, and has proved to be a successful treatment for some common pediatric conditions, including bedwetting. Similar to oxytocin, it also has been shown to improve social cognition and memory in people who do not have autism. The researchers will test the effects of vasopressin on social impairments in 50 boys and girls with autism, ages 6 to 12 years old. The study will last four weeks for each participant. Participants will receive either vasopressin or a placebo nasal spray. At the end of this phase of the study, those who received the placebo will have the option of participating in a four-week trial during which they will be given vasopressin. Stanford is the only site for the study. Participants do not need to live locally but will need to come to the Stanford University Department of Psychiatry and Behavioral Sciences for study visits.

Condition or Disease	Intervention/Treatment	Phase
Autism Spectrum Disorders	Drug: Vasopressin; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 68 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Randomized Placebo-controlled Trial of Vasopressin Treatment for Social Deficits in Children With Autism
• Actual Study Start Date: Dec 1, 2013
• Actual Primary Completion Date: May 30, 2017
• Actual Study Completion Date: May 30, 2017

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Placebo Nasal Spray	Drug: Placebo
Active Comparator: Vasopressin Vasopressin Nasal Spray	Drug: Vasopressin; Participants aged 6 to 9.5 years of age will receive the maximum dose of 24 IU (12 IU twice daily). Participants aged 9.6 to 12 years of age will receive the maximum dose of 32 IU (16 IU twice daily).

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Parent Rated Social Responsiveness Scale, 2nd Edition (SRS-2) T-Score After Treatment. [Baseline; Week 4]

   Social Responsiveness Scale, 2nd Edition (SRS) scores measure social abilities with lower scores meaning better social abilities. (T-Score Range: 37- above 90 )

Secondary Outcome Measures

1. Change From Baseline in Clinical Global Impression (CGI) Severity, Social and Communication Scores During Treatment. [Baseline; Week 4]

   Higher Scores on the CGI severity scale mean more greater social and communication deficits (Range 1-7)

2. Change From Baseline in Reading the Mind in the Eyes Test, Child Version (RMET-child) Scores During Treatment. [Baseline; Week 4]

   Higher scores mean better ability to read emotions and lower scores mean worse ability to read emotions. Range 0-28.

3. Change From Baseline in Laboratory Based Facial Emotion Recognition Abilities During Treatment. [Baseline; Week 4]

   Higher scores mean better facial emotion recognition abilities. Lower scores mean worse facial emotion recognition abilities (Range: 0-42).

4. Change From Baseline in Parent Rated Repetitive Behavior Scale Revised (RBS-R) Scores During Treatment. [Baseline; Week 4]

   Higher scores on the Repetitive Behavior Scale- Revised mean higher levels of repetitive and restricted behaviors. (Raw Score Total Range: 0 - 129)

5. Change From Baseline in Parent Rated Spence Children's Anxiety Scale (SCAS) During Treatment. [Baseline; Week 4]

   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)

6. Number of Participants With Side Effects Assessed Using Parent Rated Dosage Record Treatment Emergent Symptom Scale (DOTES) Scores During Treatment [Baseline through Week 4]

   Dosage Record Treatment Emergent Symptom Scale (DOTES) side effects reported by parents during 4-weeks of treatment. Participant Counts are used.

7. Change From Baseline on the Overt Aggression Scale (OAS) During Treatment. [Baseline through Week 4]

   Count of participants reporting an increase of aggression during treatment compared to baseline (pretreatment).

8. Change From Baseline in Heart Rate After Treatment. [Baseline; Week 4]

   Sitting heart rate (beats per minute).

9. Change From Baseline in Parent Rated Aberrant Behavior Checklist (ABC) Scores During Treatment. [Baseline; 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.

10. Change From Baseline in Parent Rated Pediatric Quality of Life (PedQL) Inventory Scores During Treatment. [Baseline; Week 4]

    Higher scores mean better quality of life and lower scores mean worse quality of life (Range: Minimum=0; Maximum=100).

11. Change From Baseline in Parent Rated Vineland Adaptive Behavior Scales Second Edition (VABS-II) - Social and Communication Subscales During Treatment. [Baseline; Week 4]

    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.

12. Change From Baseline in Clinical Chemistry Labs (NA+, K+, Cl-) During Treatment. [Baseline; Week 4]

    Clinical chemistry labs(sodium, potassium, chloride)

13. Change From Baseline in Laboratory Based Eye-gaze to Social Cues During Treatment. [Baseline; Week 4]

14. Change From Baseline in Laboratory Based Social Mimicry Abilities During Treatment. [Baseline; Week 4]

15. Change From Baseline in Blood Pressure After Treatment [Baseline; Week 4]

    Sitting Systolic and Diastolic blood pressure.

16. Change From Baseline in Body Weight After Treatment. [Baseline; Week 4]

17. Change From Baseline in Body Temperature After Treatment [Baseline; Week 4]

18. Change From Baseline in the Awareness of Social Inference Test Revised (TASIT-R) Scores During Treatment. [Baseline, Week 4]

19. Change From Baseline in a Developmental Neuropsychological Assessment, Second Edition. (NEPSY-II) Affect Recognition Scores During Treatment. [Baseline; Week 4]

    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.

20. Change From Baseline in Plasma Vasopressin Levels During Treatment. [Baseline]

    There are no clinical laboratory tests that establish a normative range for vasopressin. Measurements prior to treatment were intended to evaluate vasopressin level as a predictor of response. Plasma vasopressin levels post treatment were not quantified. Baseline vasopressin levels are included in the outcome data below.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Years to 12 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• medically healthy outpatients between 6 and 12 years of age (cut off: 12 years and 11 months)

• Intelligence Quotient (IQ) equal to or greater than 50 (Stanford-Binet)

• Social Responsiveness Scale (SRS) Total Score equal to or greater than 70

• ability to complete laboratory and cognitive testing

• diagnosis of Autism Spectrum Disorder (ASD) based on expert clinical opinion and confirmed on the Autism Diagnostic Interview-Revised (ADI-R), Autism Diagnostic Observation Schedule (ADOS)

• Clinical Global Impression (CGI) severity rating of 4 or higher

• care provider who can reliably bring participant to clinic visits, provide trustworthy ratings, and interact with the participant on a regular basis

• stable medications for at least 4 weeks

• no planned changes in psychosocial interventions during the trial

• no concurrent participation in any other clinical research trials

• willingness to provide blood samples and electrocardiogram

Exclusion Criteria:

• diagnosis of schizophrenia, schizoaffective disorder, bipolar disorder, or psychotic disorder

• regular nasal obstruction or nosebleeds

• active and unstable medical problems (e.g., migraine; asthma; seizure disorder; anaphylaxis; epilepsy; diabetes; serious liver, renal, or cardiac pathology)

• clinically significant abnormal vital signs or ECG reading

• evidence of a genetic mutation know to cause ASD (e.g., Fragile X Syndrome) or metabolic disorder

• significant hearing or vision impairments

• drinks large volumes of water (e.g., habitual or psychogenic polydipsia)

• pregnant or sexually active females not using a reliable method of contraception (urine pregnancy test will be conducted)

• history of hypersensitivity to vasopressin, its analogs (e.g., Desmopressin), or compounding preservatives (e.g., chlorobutanol)

• current use of any medications known to interact with vasopressin including: 1) carbamazepine (i.e., Tegretol); chlorpropamide; clofibrate; urea; fludrocortisone; tricyclic antidepressants (all of which may potentiate the antidiuretic effect of vasopressin when used concurrently); 2) demeclocycline; norepinephrine; lithium; heparin; alcohol (all of which may decrease the antidiuretic effect of vasopressin when used concurrently); 3) ganglionic blocking agents including benzohexonium, chlorisondamine, pentamine (all of which may produce a marked increase in sensitivity to the pressor effects of vasopressin)

• prior or current use of vasopressin

• abnormal chemistry result

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford University School of Medicine; Psychiatry and Behavioral Sciences	Stanford	California	United States	94305

Sponsors and Collaborators

• Stanford University
• National Institute of Mental Health (NIMH)

Investigators

• Principal Investigator: Antonio Y Hardan, MD, Stanford University
• Principal Investigator: Karen J Parker, PhD, Stanford University

Study Documents (Full-Text)

• Statistical Analysis Plan - Jan 11, 2019
• Study Protocol - Aug 2, 2016

More Information

Publications

None provided.

• Responsible Party: Antonio Hardan, MD, Stanford University
• ClinicalTrials.gov Identifier: NCT01962870
• Other Study ID Numbers: IRB-26034; R21MH100387-01
• First Posted: Oct 14, 2013
• Last Update Posted: May 24, 2019
• Last Verified: May 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Autistic Disorder; Autism Spectrum Disorder; Vasopressins; Arginine Vasopressin

Study Results

Participant Flow

Recruitment Details	This study was conducted in the Autism and Developmental Disorders Clinic in the Division of Child and Adolescent Psychiatry at Stanford University. Recruitment began in December 2013 and ended in May 2017.
Pre-assignment Detail	68 participants signed the consent form and enrolled in the study. Of those 68 participants, 27 participants did not meet the eligibility criteria for the study and 11 participants declined to participate prior to randomization. 30 participants were randomized.

Arm/Group Title	Placebo	Vasopressin
Arm/Group Description	Placebo Nasal Spray Placebo	Vasopressin Nasal Spray Vasopressin: Participants aged 6 to 9.5 years of age will receive the maximum dose of 24 IU (12 IU twice daily). Participants aged 9.6 to 12 years of age will receive the maximum dose of 32 IU (16 IU twice daily).
Period Title: Overall Study
STARTED	13	17
COMPLETED	13	17
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Placebo	Vasopressin	Total
Arm/Group Description	Placebo Nasal Spray Placebo	Vasopressin Nasal Spray Vasopressin: Participants aged 6 to 9.5 years of age will receive the maximum dose of 24 IU (12 IU twice daily). Participants aged 9.6 to 12 years of age will receive the maximum dose of 32 IU (16 IU twice daily).	Total of all reporting groups
Overall Participants	13	17	30
Age (Count of Participants)
<=18 years	13 100%	17 100%	30 100%
Between 18 and 65 years	0 0%	0 0%	0 0%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	2 15.4%	3 17.6%	5 16.7%
Male	11 84.6%	14 82.4%	25 83.3%
Race/Ethnicity, Customized (Count of Participants)
Caucasian	11 84.6%	8 47.1%	19 63.3%
Other	2 15.4%	9 52.9%	11 36.7%
Region of Enrollment (participants) [Number]
United States	13 100%	17 100%	30 100%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Parent Rated Social Responsiveness Scale, 2nd Edition (SRS-2) T-Score After Treatment.
Description	Social Responsiveness Scale, 2nd Edition (SRS) scores measure social abilities with lower scores meaning better social abilities. (T-Score Range: 37- above 90 )
Time Frame	Baseline; Week 4

Outcome Measure Data

Analysis Population Description

Participants who completed the protocol are included in the analysis.

Arm/Group Title	Placebo	Vasopressin
Arm/Group Description	Placebo Nasal Spray Placebo	Vasopressin Nasal Spray Vasopressin: Participants aged 6 to 9.5 years of age will receive the maximum dose of 24 IU (12 IU twice daily). Participants aged 9.6 to 12 years of age will receive the maximum dose of 32 IU (16 IU twice daily).
Measure Participants	13	17
Least Squares Mean (Standard Error) [units on a scale]	10.8 (2.11)	17.6 (1.37)

2. Secondary Outcome

Title	Change From Baseline in Clinical Global Impression (CGI) Severity, Social and Communication Scores During Treatment.
Description	Higher Scores on the CGI severity scale mean more greater social and communication deficits (Range 1-7)
Time Frame	Baseline; Week 4

Outcome Measure Data

Analysis Population Description

Participants with available data are included.

Arm/Group Title	Placebo	Vasopressin
Arm/Group Description	Placebo Nasal Spray Placebo	Vasopressin Nasal Spray Vasopressin: Participants aged 6 to 9.5 years of age will receive the maximum dose of 24 IU (12 IU twice daily). Participants aged 9.6 to 12 years of age will receive the maximum dose of 32 IU (16 IU twice daily).
Measure Participants	13	17
Least Squares Mean (Standard Error) [units on a scale]	0.712 (0.202)	0.873 (0.126)

3. Secondary Outcome

Title	Change From Baseline in Reading the Mind in the Eyes Test, Child Version (RMET-child) Scores During Treatment.
Description	Higher scores mean better ability to read emotions and lower scores mean worse ability to read emotions. Range 0-28.
Time Frame	Baseline; Week 4

Outcome Measure Data

Analysis Population Description

Participants with available data are included in the analysis.

Arm/Group Title	Placebo	Vasopressin
Arm/Group Description	Placebo Nasal Spray Placebo	Vasopressin Nasal Spray Vasopressin: Participants aged 6 to 9.5 years of age will receive the maximum dose of 24 IU (12 IU twice daily). Participants aged 9.6 to 12 years of age will receive the maximum dose of 32 IU (16 IU twice daily).
Measure Participants	13	17
Mean (Standard Error) [units on a scale]	-1.28 (1.24)	4.04 (1.63)

4. Secondary Outcome

Title	Change From Baseline in Laboratory Based Facial Emotion Recognition Abilities During Treatment.
Description	Higher scores mean better facial emotion recognition abilities. Lower scores mean worse facial emotion recognition abilities (Range: 0-42).
Time Frame	Baseline; Week 4

Outcome Measure Data

Analysis Population Description

Participants with available data are included in the analysis.

Arm/Group Title	Placebo	Vasopressin
Arm/Group Description	Placebo Nasal Spray Placebo	Vasopressin Nasal Spray Vasopressin: Participants aged 6 to 9.5 years of age will receive the maximum dose of 24 IU (12 IU twice daily). Participants aged 9.6 to 12 years of age will receive the maximum dose of 32 IU (16 IU twice daily).
Measure Participants	13	17
Mean (Standard Error) [units on a scale]	-7.19 (1.81)	3.10 (2.42)

5. Secondary Outcome

Title	Change From Baseline in Parent Rated Repetitive Behavior Scale Revised (RBS-R) Scores During Treatment.
Description	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

Outcome Measure Data

Analysis Population Description

Participants with available data were analyzed.

Arm/Group Title	Placebo	Vasopressin
Arm/Group Description	Placebo Nasal Spray Placebo	Vasopressin Nasal Spray Vasopressin: Participants aged 6 to 9.5 years of age will receive the maximum dose of 24 IU (12 IU twice daily). Participants aged 9.6 to 12 years of age will receive the maximum dose of 32 IU (16 IU twice daily).
Measure Participants	13	17
Mean (Standard Error) [units on a scale]	21.3 (3.18)	17.2 (1.83)

6. Secondary Outcome

Title	Change From Baseline in Parent Rated Spence Children's Anxiety Scale (SCAS) During Treatment.
Description	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

Outcome Measure Data

Analysis Population Description

Participants with available data were analyzed.

Arm/Group Title	Placebo	Vasopressin
Arm/Group Description	Placebo Nasal Spray Placebo	Vasopressin Nasal Spray Vasopressin: Participants aged 6 to 9.5 years of age will receive the maximum dose of 24 IU (12 IU twice daily). Participants aged 9.6 to 12 years of age will receive the maximum dose of 32 IU (16 IU twice daily).
Measure Participants	13	17
Least Squares Mean (Standard Error) [units on a scale]	9.14 (2.68)	17.9 (1.66)

7. Secondary Outcome

Title	Number of Participants With Side Effects Assessed Using Parent Rated Dosage Record Treatment Emergent Symptom Scale (DOTES) Scores During Treatment
Description	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

Outcome Measure Data

Analysis Population Description

Participants who completed the protocol are included in the analysis.

Arm/Group Title	Placebo	Vasopressin
Arm/Group Description	Placebo Nasal Spray Placebo	Vasopressin Nasal Spray Vasopressin: Participants aged 6 to 9.5 years of age will receive the maximum dose of 24 IU (12 IU twice daily). Participants aged 9.6 to 12 years of age will receive the maximum dose of 32 IU (16 IU twice daily).
Measure Participants	13	17
Fever	1 7.7%	2 11.8%
Cough	0 0%	1 5.9%
Body Ache	0 0%	1 5.9%
Excitement/Agitation	1 7.7%	0 0%
Insomnia	1 7.7%	4 23.5%
Increased Motor Activity	0 0%	4 23.5%
Depressive Affect	1 7.7%	2 11.8%
Headache	0 0%	2 11.8%
Drowsiness	3 23.1%	1 5.9%
Decreased Motor Activity	2 15.4%	1 5.9%
Aggression	1 7.7%	1 5.9%
Akathisia	0 0%	1 5.9%
Head Banging	0 0%	1 5.9%
Dizziness	1 7.7%	0 0%
Lethargy/Tiredness	1 7.7%	0 0%
Nasal Congestion	4 30.8%	3 17.6%
Dry Mouth	3 23.1%	1 5.9%
Blurred Vision	1 7.7%	1 5.9%
Ear Infection	1 7.7%	0 0%
Runny Nose	1 7.7%	0 0%
Sore Throat	1 7.7%	0 0%
Cold Sore	1 7.7%	0 0%
Decreased Appetite	5 38.5%	4 23.5%
Nausea/Vomiting	2 15.4%	2 11.8%
Constipation	0 0%	1 5.9%
Diarrhea	1 7.7%	0 0%
Increased Urination	1 7.7%	1 5.9%
Bed Wetting	0 0%	1 5.9%
Skin Rash	1 7.7%	1 5.9%
Bug Bite	0 0%	1 5.9%
Skin Burn	1 7.7%	0 0%

8. Secondary Outcome

Title	Change From Baseline on the Overt Aggression Scale (OAS) During Treatment.
Description	Count of participants reporting an increase of aggression during treatment compared to baseline (pretreatment).
Time Frame	Baseline through Week 4

Outcome Measure Data

Analysis Population Description

Participants with available data are included in the analysis.

Arm/Group Title	Placebo	Vasopressin
Arm/Group Description	Placebo Nasal Spray Placebo	Vasopressin Nasal Spray Vasopressin: Participants aged 6 to 9.5 years of age will receive the maximum dose of 24 IU (12 IU twice daily). Participants aged 9.6 to 12 years of age will receive the maximum dose of 32 IU (16 IU twice daily).
Measure Participants	13	17
Count of Participants [Participants]	1 7.7%	1 5.9%

9. Secondary Outcome

Title	Change From Baseline in Heart Rate After Treatment.
Description	Sitting heart rate (beats per minute).
Time Frame	Baseline; Week 4

Outcome Measure Data

Analysis Population Description

Participants who completed the protocol are included in the analysis.

Arm/Group Title	Placebo	Vasopressin
Arm/Group Description	Placebo Nasal Spray Placebo	Vasopressin Nasal Spray Vasopressin: Participants aged 6 to 9.5 years of age will receive the maximum dose of 24 IU (12 IU twice daily). Participants aged 9.6 to 12 years of age will receive the maximum dose of 32 IU (16 IU twice daily).
Measure Participants	13	17
Least Squares Mean (Standard Error) [Beats per minute]	7.5 (4.43)	1.9 (3.87)

10. Secondary Outcome

Title	Change From Baseline in Parent Rated Aberrant Behavior Checklist (ABC) Scores During Treatment.
Description	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

Outcome Measure Data

Analysis Population Description

Participants with available data were included in analysis.

Arm/Group Title	Placebo	Vasopressin
Arm/Group Description	Placebo Nasal Spray Placebo	Vasopressin Nasal Spray Vasopressin: Participants aged 6 to 9.5 years of age will receive the maximum dose of 24 IU (12 IU twice daily). Participants aged 9.6 to 12 years of age will receive the maximum dose of 32 IU (16 IU twice daily).
Measure Participants	13	17
Irritability Baseline	14.00 (10.23)	8.29 (7.40)
Irritability Week 4	8.38 (7.23)	6.24 (7.05)
Lethargy Baseline	14.77 (10.69)	10.76 (6.32)
Lethargy Week 4	12.77 (9.81)	7.41 (6.88)
Stereotypy Baseline	5.08 (5.36)	5.18 (3.88)
Stereotypy Week 4	4.54 (4.91)	3.53 (3.59)
Hyperactivity Baseline	21.38 (9.17)	16.00 (11.69)
Hyperactivity Week 4	14.54 (7.34)	12.29 (9.06)
Inappropriate Speech Baseline	4.62 (3.74)	3.94 (2.86)
Inappropriate Speech Week 4	3.69 (3.52)	3.41 (3.08)

11. Secondary Outcome

Title	Change From Baseline in Parent Rated Pediatric Quality of Life (PedQL) Inventory Scores During Treatment.
Description	Higher scores mean better quality of life and lower scores mean worse quality of life (Range: Minimum=0; Maximum=100).
Time Frame	Baseline; Week 4

Outcome Measure Data

Analysis Population Description

Participants with available data were analyzed.

Arm/Group Title	Placebo	Vasopressin
Arm/Group Description	Placebo Nasal Spray Placebo	Vasopressin Nasal Spray Vasopressin: Participants aged 6 to 9.5 years of age will receive the maximum dose of 24 IU (12 IU twice daily). Participants aged 9.6 to 12 years of age will receive the maximum dose of 32 IU (16 IU twice daily).
Measure Participants	13	17
Baseline	57.14 (16.67)	64.53 (13.86)
Week 4	65.96 (14.93)	74.52 (15.38)

12. Secondary Outcome

Title	Change From Baseline in Parent Rated Vineland Adaptive Behavior Scales Second Edition (VABS-II) - Social and Communication Subscales During Treatment.
Description	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

Outcome Measure Data

Analysis Population Description

Not all participants were able to fully complete the measure so not all of the numbers analyzed are the same.

Arm/Group Title	Placebo	Vasopressin
Arm/Group Description	Placebo Nasal Spray Placebo	Vasopressin Nasal Spray Vasopressin: Participants aged 6 to 9.5 years of age will receive the maximum dose of 24 IU (12 IU twice daily). Participants aged 9.6 to 12 years of age will receive the maximum dose of 32 IU (16 IU twice daily).
Measure Participants	13	17
Baseline Social Standard Score	61.33 (13.93)	71.08 (14.38)
Week 4 Social Standard Score	62.25 (7.78)	79.67 (16.83)
Baseline Communication Standard Score	75.67 (13.57)	74.77 (8.60)
Week 4 Communication Standard Score	77.40 (10.55)	81.12 (14.26)

13. Secondary Outcome

Title	Change From Baseline in Clinical Chemistry Labs (NA+, K+, Cl-) During Treatment.
Description	Clinical chemistry labs(sodium, potassium, chloride)
Time Frame	Baseline; Week 4

Outcome Measure Data

Analysis Population Description

Participants with available data are included in the analysis.

Arm/Group Title	Placebo	Vasopressin
Arm/Group Description	Placebo Nasal Spray Placebo	Vasopressin Nasal Spray Vasopressin: Participants aged 6 to 9.5 years of age will receive the maximum dose of 24 IU (12 IU twice daily). Participants aged 9.6 to 12 years of age will receive the maximum dose of 32 IU (16 IU twice daily).
Measure Participants	13	17
Change From Baseline in Sodium	0.15 (0.72)	0.24 (0.63)
Change from Baseline in Potassium	0.06 (0.13)	0.15 (0.11)
Change from Baseline on Chloride	-0.31 (0.64)	1.0 (0.56)

14. Secondary Outcome

Title	Change From Baseline in Laboratory Based Eye-gaze to Social Cues During Treatment.
Time Frame	Baseline; Week 4

Outcome Measure Data

Analysis Population Description

Data were not not collected for this outcome.

Arm/Group Title	Placebo	Vasopressin
Arm/Group Description	Placebo Nasal Spray Placebo	Vasopressin Nasal Spray Vasopressin: Participants aged 6 to 9.5 years of age will receive the maximum dose of 24 IU (12 IU twice daily). Participants aged 9.6 to 12 years of age will receive the maximum dose of 32 IU (16 IU twice daily).
Measure Participants	0	0

15. Secondary Outcome

Title	Change From Baseline in Laboratory Based Social Mimicry Abilities During Treatment.
Time Frame	Baseline; Week 4

Outcome Measure Data

Analysis Population Description

Data were not not collected for this outcome.

Arm/Group Title	Placebo	Vasopressin
Arm/Group Description	Placebo Nasal Spray Placebo	Vasopressin Nasal Spray Vasopressin: Participants aged 6 to 9.5 years of age will receive the maximum dose of 24 IU (12 IU twice daily). Participants aged 9.6 to 12 years of age will receive the maximum dose of 32 IU (16 IU twice daily).
Measure Participants	0	0

16. Secondary Outcome

Title	Change From Baseline in Blood Pressure After Treatment
Description	Sitting Systolic and Diastolic blood pressure.
Time Frame	Baseline; Week 4

Outcome Measure Data

Analysis Population Description

Participants with available data are included in the analysis.

Arm/Group Title	Placebo	Vasopressin
Arm/Group Description	Placebo Nasal Spray Placebo	Vasopressin Nasal Spray Vasopressin: Participants aged 6 to 9.5 years of age will receive the maximum dose of 24 IU (12 IU twice daily). Participants aged 9.6 to 12 years of age will receive the maximum dose of 32 IU (16 IU twice daily).
Measure Participants	13	17
Change from Baseline in Systolic Blood Pressure	-1.1 (2.89)	5.5 (2.53)
Change from Baseline in Diastolic Blood Pressure	-1.8 (2.39)	3.2 (2.09)

17. Secondary Outcome

Title	Change From Baseline in Body Weight After Treatment.
Time Frame	Baseline; Week 4

Outcome Measure Data

Analysis Population Description

Participants with available data are included in the analysis.

Arm/Group Title	Placebo	Vasopressin
Arm/Group Description	Placebo Nasal Spray Placebo	Vasopressin Nasal Spray Vasopressin: Participants aged 6 to 9.5 years of age will receive the maximum dose of 24 IU (12 IU twice daily). Participants aged 9.6 to 12 years of age will receive the maximum dose of 32 IU (16 IU twice daily).
Measure Participants	13	17
Least Squares Mean (Standard Error) [kilograms]	0.2 (0.34)	0.3 (0.30)

18. Secondary Outcome

Title	Change From Baseline in Body Temperature After Treatment
Time Frame	Baseline; Week 4

Outcome Measure Data

Analysis Population Description

Participants with available data are included in the analysis.

Arm/Group Title	Placebo	Vasopressin
Arm/Group Description	Placebo Nasal Spray Placebo	Vasopressin Nasal Spray Vasopressin: Participants aged 6 to 9.5 years of age will receive the maximum dose of 24 IU (12 IU twice daily). Participants aged 9.6 to 12 years of age will receive the maximum dose of 32 IU (16 IU twice daily).
Measure Participants	13	17
Least Squares Mean (Standard Error) [Degrees (Farenheit)]	-0.2 (0.19)	0.2 (0.17)

19. Secondary Outcome

Title	Change From Baseline in the Awareness of Social Inference Test Revised (TASIT-R) Scores During Treatment.
Time Frame	Baseline, Week 4

Outcome Measure Data

Analysis Population Description

Data were not not collected for this outcome.

Arm/Group Title	Placebo	Vasopressin
Arm/Group Description	Placebo Nasal Spray Placebo	Vasopressin Nasal Spray Vasopressin: Participants aged 6 to 9.5 years of age will receive the maximum dose of 24 IU (12 IU twice daily). Participants aged 9.6 to 12 years of age will receive the maximum dose of 32 IU (16 IU twice daily).
Measure Participants	0	0

20. Secondary Outcome

Title	Change From Baseline in a Developmental Neuropsychological Assessment, Second Edition. (NEPSY-II) Affect Recognition Scores During Treatment.
Description	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

Outcome Measure Data

Analysis Population Description

Participants with available data were included.

Arm/Group Title	Placebo	Vasopressin
Arm/Group Description	Placebo Nasal Spray Placebo	Vasopressin Nasal Spray Vasopressin: Participants aged 6 to 9.5 years of age will receive the maximum dose of 24 IU (12 IU twice daily). Participants aged 9.6 to 12 years of age will receive the maximum dose of 32 IU (16 IU twice daily).
Measure Participants	13	17
Least Squares Mean (Standard Error) [units on a scale]	-2.58 (1.9)	0.094 (2.20)

21. Secondary Outcome

Title	Change From Baseline in Plasma Vasopressin Levels During Treatment.
Description	There are no clinical laboratory tests that establish a normative range for vasopressin. Measurements prior to treatment were intended to evaluate vasopressin level as a predictor of response. Plasma vasopressin levels post treatment were not quantified. Baseline vasopressin levels are included in the outcome data below.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Participants with available data were included in the analysis.

Arm/Group Title	Placebo	Vasopressin
Arm/Group Description	Placebo Nasal Spray Placebo	Vasopressin Nasal Spray Vasopressin: Participants aged 6 to 9.5 years of age will receive the maximum dose of 24 IU (12 IU twice daily). Participants aged 9.6 to 12 years of age will receive the maximum dose of 32 IU (16 IU twice daily).
Measure Participants	13	17
Mean (Standard Error) [pg/ml]	1.28 (0.29)	1.32 (0.25)

Adverse Events

Time Frame	4 weeks
Adverse Event Reporting Description	Dosage Record Treatment Emergent Symptom Scale (DOTES) and Overt Aggression Scale (OAS) were used to assess side effects.
Arm/Group Title	Placebo		Vasopressin
Arm/Group Description	Placebo Nasal Spray Placebo		Vasopressin Nasal Spray Vasopressin: Participants aged 6 to 9.5 years of age will receive the maximum dose of 24 IU (12 IU twice daily). Participants aged 9.6 to 12 years of age will receive the maximum dose of 32 IU (16 IU twice daily).
All Cause Mortality
	Placebo		Vasopressin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/13 (0%)		0/17 (0%)
Serious Adverse Events
	Placebo		Vasopressin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/13 (0%)		0/17 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Vasopressin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/13 (92.3%)		13/17 (76.5%)
Ear and labyrinth disorders
Ear Infection	1/13 (7.7%)		0/17 (0%)
Eye disorders
Blurred Vision	1/13 (7.7%)		1/17 (5.9%)
Gastrointestinal disorders
Decreased Appetite	5/13 (38.5%)		4/17 (23.5%)
Nausea/Vomiting	2/13 (15.4%)		2/17 (11.8%)
Constipation	0/13 (0%)		1/17 (5.9%)
Diarrhea	1/13 (7.7%)		0/17 (0%)
General disorders
Fever	1/13 (7.7%)		2/17 (11.8%)
Cough	0/13 (0%)		1/17 (5.9%)
Body Ache	0/13 (0%)		1/17 (5.9%)
Nasal Congestion	4/13 (30.8%)		3/17 (17.6%)
Dry Mouth	3/13 (23.1%)		1/17 (5.9%)
Runny Nose	1/13 (7.7%)		0/17 (0%)
Sore Throat	1/13 (7.7%)		0/17 (0%)
Increased Urination	1/13 (7.7%)		1/17 (5.9%)
Bed Wetting	0/13 (0%)		1/17 (5.9%)
Nervous system disorders
Insomnia	1/13 (7.7%)		4/17 (23.5%)
Increased Motor Activity	0/13 (0%)		4/17 (23.5%)
Headache	0/13 (0%)		2/17 (11.8%)
Drowsiness	3/13 (23.1%)		1/17 (5.9%)
Decreased Motor Activity	2/13 (15.4%)		1/17 (5.9%)
Akathisia	0/13 (0%)		1/17 (5.9%)
Dizziness	1/13 (7.7%)		0/17 (0%)
Lethargy/Tiredness	1/13 (7.7%)		0/17 (0%)
Psychiatric disorders
Excitement/Agitation	1/13 (7.7%)		4/17 (23.5%)
Depressive Affect	1/13 (7.7%)		2/17 (11.8%)
Aggression	1/13 (7.7%)		1/17 (5.9%)
Head Banging	0/13 (0%)		1/17 (5.9%)
Skin and subcutaneous tissue disorders
Cold Sore	1/13 (7.7%)		0/17 (0%)
Skin Rash	1/13 (7.7%)		1/17 (5.9%)
Bug Bite	0/13 (0%)		1/17 (5.9%)
Skin Burn	1/13 (7.7%)		0/17 (0%)

Limitations/Caveats

The final sample was 83% male and was not statistically powered to detect sex differences in treatment response. Participants were permitted to take other medications during the intervention. Many of our outcome measures relied on parent report.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.