Clinical trial NCT01962870: The Role of Vasopressin in the Social Deficits of Autism
Official title: Randomized Placebo-controlled Trial of Vasopressin Treatment for Social Deficits in Children With Autism
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Autism Spectrum Disorders
Lead sponsor: Stanford University
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
First posted: 2013-10-14
Enrollment: 68
Sex: ALL
Minimum age (years): 6
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Change From Baseline in Parent Rated Social Responsiveness Scale, 2nd Edition (SRS-2) T-Score After Treatment.
timeFrame: Baseline; Week 4
Secondary outcomes:
measure: Change From Baseline in Clinical Global Impression (CGI) Severity, Social and Communication Scores During Treatment.
timeFrame: Baseline; Week 4
measure: Change From Baseline in Reading the Mind in the Eyes Test, Child Version (RMET-child) Scores During Treatment.
timeFrame: Baseline; Week 4
measure: Change From Baseline in Laboratory Based Facial Emotion Recognition Abilities During Treatment.
timeFrame: Baseline; Week 4
measure: Change From Baseline in Parent Rated Repetitive Behavior Scale Revised (RBS-R) Scores During Treatment.
timeFrame: Baseline; Week 4
measure: Change From Baseline in Parent Rated Spence Children's Anxiety Scale (SCAS) During Treatment.
timeFrame: Baseline; Week 4
measure: Number of Participants With Side Effects Assessed Using Parent Rated Dosage Record Treatment Emergent Symptom Scale (DOTES) Scores During Treatment
timeFrame: Baseline through Week 4
measure: Change From Baseline on the Overt Aggression Scale (OAS) During Treatment.
timeFrame: Baseline through Week 4
measure: Change From Baseline in Heart Rate After Treatment.
timeFrame: Baseline; Week 4
measure: Change From Baseline in Parent Rated Aberrant Behavior Checklist (ABC) Scores During Treatment.
timeFrame: Baseline; Week 4
measure: Change From Baseline in Parent Rated Pediatric Quality of Life (PedQL) Inventory Scores During Treatment.
timeFrame: Baseline; Week 4
measure: Change From Baseline in Parent Rated Vineland Adaptive Behavior Scales Second Edition (VABS-II) - Social and Communication Subscales During Treatment.
timeFrame: Baseline; Week 4
measure: Change From Baseline in Clinical Chemistry Labs (NA+, K+, Cl-) During Treatment.
timeFrame: Baseline; Week 4
measure: Change From Baseline in Laboratory Based Eye-gaze to Social Cues During Treatment.
timeFrame: Baseline; Week 4
measure: Change From Baseline in Laboratory Based Social Mimicry Abilities During Treatment.
timeFrame: Baseline; Week 4
measure: Change From Baseline in Blood Pressure After Treatment
timeFrame: Baseline; Week 4
measure: Change From Baseline in Body Weight After Treatment.
timeFrame: Baseline; Week 4
measure: Change From Baseline in Body Temperature After Treatment
timeFrame: Baseline; Week 4
measure: Change From Baseline in the Awareness of Social Inference Test Revised (TASIT-R) Scores During Treatment.
timeFrame: Baseline, Week 4
measure: Change From Baseline in a Developmental Neuropsychological Assessment, Second Edition. (NEPSY-II) Affect Recognition Scores During Treatment.
timeFrame: Baseline; Week 4
measure: Change From Baseline in Plasma Vasopressin Levels During Treatment.
timeFrame: Baseline
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University School of Medicine; Psychiatry and Behavioral Sciences
state: California
Study officials:
affiliation: Stanford University
name: Antonio Y Hardan, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Stanford University
name: Karen J Parker, PhD
role: PRINCIPAL_INVESTIGATOR
References: