The Role of Vasopressin in the Social Deficits of Autism

• ClinicalTrials.gov Identifier: NCT01962870
• Recruitment Status: Completed
• First Posted: October 14, 2013
• Results First Posted: May 24, 2019
• Last Update Posted: May 24, 2019
• Sponsor: Stanford University
• Collaborator: National Institute of Mental Health (NIMH)
• Information provided by (Responsible Party): Antonio Hardan, Stanford University

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 (Clinical Trial)
• 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: December 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. [ Time Frame: 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. [ Time Frame: 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. [ Time Frame: 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. [ Time Frame: 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. [ Time Frame: 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. [ Time Frame: 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 [ Time Frame: 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. [ Time Frame: 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. [ Time Frame: Baseline; Week 4 ]
   Sitting heart rate (beats per minute).
9. Change From Baseline in Parent Rated Aberrant Behavior Checklist (ABC) Scores During Treatment. [ Time Frame: 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. [ Time Frame: 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. [ Time Frame: 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. [ Time Frame: Baseline; Week 4 ]
    Clinical chemistry labs(sodium, potassium, chloride)
13. Change From Baseline in Laboratory Based Eye-gaze to Social Cues During Treatment. [ Time Frame: Baseline; Week 4 ]
14. Change From Baseline in Laboratory Based Social Mimicry Abilities During Treatment. [ Time Frame: Baseline; Week 4 ]
15. Change From Baseline in Blood Pressure After Treatment [ Time Frame: Baseline; Week 4 ]
    Sitting Systolic and Diastolic blood pressure.
16. Change From Baseline in Body Weight After Treatment. [ Time Frame: Baseline; Week 4 ]
17. Change From Baseline in Body Temperature After Treatment [ Time Frame: Baseline; Week 4 ]
18. Change From Baseline in the Awareness of Social Inference Test Revised (TASIT-R) Scores During Treatment. [ Time Frame: Baseline, Week 4 ]
19. Change From Baseline in a Developmental Neuropsychological Assessment, Second Edition. (NEPSY-II) Affect Recognition Scores During Treatment. [ Time Frame: 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. [ Time Frame: 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

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

Criteria

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

United States, California

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)

Documents provided by Antonio Hardan, Stanford University:

Statistical Analysis Plan  [PDF] January 11, 2019

Study Protocol  [PDF] August 2, 2016

More Information

• Responsible Party: Antonio Hardan, MD, Stanford University
• ClinicalTrials.gov Identifier: NCT01962870
• Other Study ID Numbers: IRB-26034; R21MH100387-01 ( U.S. NIH Grant/Contract )
• First Posted: October 14, 2013
• Results First Posted: May 24, 2019
• Last Update Posted: May 24, 2019
• Last Verified: May 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Additional relevant MeSH terms:

Autistic Disorder; Autism Spectrum Disorder; Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders; Vasopressins; Arginine Vasopressin; Hemostatics; Coagulants; Vasoconstrictor Agents; Antidiuretic Agents; Natriuretic Agents; Physiological Effects of Drugs