The Role of Vasopressin in the Social Deficits of Autism

NCT01962870 | Completed Phase 2 Results DMC

• 2 other identifiers: IRB-26034R21MH100387-01
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 1

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.

Conditions

Autism Spectrum Disorders

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Parent Rated Social Responsiveness Scale, 2nd Edition (SRS-2) T-Score After Treatment.

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

  Baseline; Week 4

Secondary Outcomes (20)

• Change From Baseline in Clinical Global Impression (CGI) Severity, Social and Communication Scores During Treatment.

  Baseline; Week 4

• Change From Baseline in Reading the Mind in the Eyes Test, Child Version (RMET-child) Scores During Treatment.

  Baseline; Week 4

• Change From Baseline in Laboratory Based Facial Emotion Recognition Abilities During Treatment.

  Baseline; Week 4

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

  Baseline; Week 4

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

  Baseline; Week 4

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Placebo Nasal Spray

Drug: Placebo

Vasopressin

ACTIVE COMPARATOR

Vasopressin Nasal Spray

Drug: Vasopressin

Interventions

Vasopressin DRUG

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).

Vasopressin

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 6 Years - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Stanford University: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

Stanford University School of Medicine; Psychiatry and Behavioral Sciences

Stanford, California, 94305, United States

Location

Related Publications (1)

• Iffland M, Livingstone N, Jorgensen M, Hazell P, Gillies D. Pharmacological intervention for irritability, aggression, and self-injury in autism spectrum disorder (ASD). Cochrane Database Syst Rev. 2023 Oct 9;10(10):CD011769. doi: 10.1002/14651858.CD011769.pub2.

  PMID: 37811711 DERIVED

MeSH Terms

Conditions

Autism Spectrum Disorder

Interventions

Vasopressins

Condition Hierarchy (Ancestors)

Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Pituitary Hormones, Posterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Limitations and 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.

Results Point of Contact

• Title: Antonio Hardan, MD
• Organization: Stanford University

hardanay@stanford.edu

(650) 736-1235

Study Officials

• Antonio Y Hardan, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

• Karen J Parker, PhD

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: October 8, 2013
• First Posted: October 14, 2013
• Study Start: December 1, 2013
• Primary Completion: May 30, 2017
• Study Completion: May 30, 2017
• Last Updated: May 24, 2019
• Results First Posted: May 24, 2019

Record last verified: 2019-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)