Intranasal Vasopressin Treatment in Children With Autism

The purpose of this clinical trial is to investigate the effectiveness of vasopressin nasal spray for treating symptoms associated with autism. Vasopressin is a hormone that is produced naturally within the body and has been implicated in regulating social behaviors. It has been proposed that administration of the hormone may also help improve social functioning in individuals with autism.

Study Overview

• Status: Completed
• Conditions: Autism Spectrum Disorder; Autism; ASD
• Intervention / Treatment: Drug: Placebo; Drug: Vasopressin (USP) Injectable Solution [Vasostrict]

• Study Type: Interventional
• Enrollment (Actual): 108
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Briana Hernandez; Phone Number: (650) 736-1235; Email: avpclinicaltrial@stanford.edu
• Study Contact Backup: Name: Esha Dhawan; Phone Number: (650) 736-1235; Email: edhawan@stanford.edu

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305-5719
      • Stanford University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 15 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Medically healthy outpatients between 6 and 17 years of age;
• Diagnostic and Statistical Manual 5th edition (DSM-5) criteria for Autism Spectrum Disorder (ASD) on the basis of clinical evaluation, confirmed with the Autism Diagnostic Interview Revised (ADI-R) and Autism Diagnostic Observation Schedule, Second Edition (ADOS-2) or Childhood Autism Rating Scale, Second Edition (CARS-2);
• males and females;
• intelligence quotient (IQ) of 40 and above;
• rating of 4 or higher on the Social Communication domain of the Clinical Global Impressions Severity (CGI-S);
• Social Responsiveness Scale-2 Total Score of 70 and above;
• care provider who can reliably bring participant to clinic visits, provide trustworthy ratings, and interacts with participant on a regular basis;
• stable concomitant psychotropic medications or medications potentially affecting vasopressin for at least 4 weeks (with the exception of fluoxetine, 6 weeks);
• no planned changes in psychosocial and biomedical interventions during the trial;
• willingness to provide blood samples and ability to participate in key study procedures (i.e., diagnostic assessments and laboratory safety measurements).

Exclusion Criteria:

• DSM-5 diagnosis of schizophrenia, schizoaffective disorder, or psychotic disorder;
• regular nasal obstruction or nosebleeds;
• unstable medical conditions such as migraine, asthma attacks, or seizures, and significant physical illness (e.g. serious liver disease, renal dysfunction, or cardiac pathology);
• clinically significant abnormal electrocardiogram reading;
• history of hypersensitivity to vasopressin, its analogs, or compounding preservatives (e.g., chlorobutanol);
• evidence of a genetic mutation known to cause ASD or intellectual disability (e.g., Fragile X Syndrome); or metabolic, or infectious etiology for ASD on the basis of medical history, neurologic history, and available tests for inborn errors of metabolism and chromosomal analysis;
• significant hearing or vision impairments;
• habitually drinks large volumes of water;
• pregnant or sexually active females not using a reliable method of contraception;
• 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);
• previous participation in a vasopressin clinical trial or current use of vasopressin;
• current use of desmopressin (DDAVP) or oxytocin.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vasopressin-Vasopressin; 8 weeks of vasopressin nasal spray (16 international units twice daily)	Drug: Vasopressin (USP) Injectable Solution [Vasostrict]; Nasal Spray
Experimental: Placebo-Vasopressin; 4 weeks of placebo nasal spray followed by 4 weeks of vasopressin nasal spray (16 international units twice daily)	Drug: Placebo; Placebo Nasal Spray; Drug: Vasopressin (USP) Injectable Solution [Vasostrict]; Nasal Spray
Placebo Comparator: Placebo-Placebo; 8 weeks of placebo nasal spray; followed by a 4 week open-label extension of vasopressin nasal spray (16 international units twice daily)	Drug: Placebo; Placebo Nasal Spray; Drug: Vasopressin (USP) Injectable Solution [Vasostrict]; Nasal Spray

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in parent rated Social Responsiveness Scale, Second Edition (SRS-2) Total Scores during treatment.	4-week; 8-week

Secondary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in Clinical Global Impression (CGI) scores during treatment.	4-week; 8-week
Change from baseline on Reading the Mind in the Eyes Test (RMET) during treatment.	4-week; 8-week
Change from baseline on the Facial Emotion Recognition Test during treatment.	4-week; 8-week
Change from baseline in parent rated Repetitive Behavior Scale Revised (RBS-R) scores during treatment.	4-week; 8-week
Change from baseline in parent rated Spence Children's Anxiety Scale (SCAS) during treatment.	4-week; 8-week
Change from baseline on the Dosage Record Treatment Emergent Symptom Scale (DOTES) during treatment.	2-week, 4-week; 6-week, 8-week
Change from baseline in Overt Aggression Scale (OAS) during treatment.	2-week, 4-week; 6-week, 8-week
Baseline vasopressin concentration predicting primary and secondary behavioral outcome measures.	4-week; 8-week
Change from baseline on vital signs (pulse) during treatment.	4-week; 8-week
Change from baseline on height during treatment.	4-week; 8-week
Change from baseline on weight during treatment.	4-week; 8-week
Change from baseline on electrocardiogram (EKG) P Duration during treatment.	4-week; 8-week
Change from baseline on electrocardiogram (EKG) PR Interval during treatment.	4-week; 8-week
Change from baseline on electrocardiogram (EKG) QRS Interval during treatment.	4-week; 8-week
Change from baseline on electrocardiogram (EKG) QT Interval during treatment.	4-week; 8-week
Change from baseline on blood clinical labs (Sodium) during treatment.	4-week; 8-week
Change from baseline on blood clinical labs (Potassium) during treatment.	4-week; 8-week
Change from baseline on blood clinical labs (Chloride) during treatment.	4-week; 8-week
Change from baseline on blood clinical labs (CO2) during treatment.	4-week; 8-week
Change from baseline on blood clinical labs (Anion Gap) during treatment.	4-week; 8-week
Change from baseline on blood clinical labs (Glucose) during treatment.	4-week; 8-week
Change from baseline on blood clinical labs (Creatinine) during treatment.	4-week; 8-week
Change from baseline on blood clinical labs (Urea Nitrogen) during treatment.	4-week; 8-week
Change from baseline on blood clinical labs (Calcium) during treatment.	4-week; 8-week
Change from baseline on blood clinical labs (Osmolality) during treatment.	4-week; 8-week
Change from baseline on urine clinical labs (Osmolality) during treatment.	4-week; 8-week
Change from baseline on vital signs (systolic blood pressure) during treatment.	4-week; 8-week
Change from baseline on vital signs (diastolic blood pressure) during treatment.	4-week; 8-week

Other Outcome Measures

Outcome Measure	Time Frame
Change from baseline in Vineland Adaptive Behavior Scales, Third Edition (VABS-3) - Social Skills and Relationships Domain during treatment.	4-week; 8-week
Change from baseline in parent rated Pediatric Quality of Life (PedsQL) inventory scores during treatment.	4-week; 8-week
Change from baseline on Eye Gaze Assessment (eye tracking) during treatment.	4-week; 8-week
Change from baseline on the Developmental Neuropsychological Assessment, Second Edition (NEPSY-II) Theory of Mind Test during treatment.	4-week; 8-week
Change from baseline the Diagnostic Analysis of Nonverbal Accuracy, Second Edition (DANVA-2) Child Voices Prosody Test during treatment.	4-week; 8-week
Change from baseline in parent rated Stanford Social Motivation Scale (also known as the Stanford Social Dimensional Scale) total scores during treatment.	4-week; 8-week
Change from baseline in Parent Rated Anxiety Scale - Autism Spectrum Disorder (PRAS-ASD) score during treatment.	4-week; 8-week
Change from baseline in parent rated Child's Sleep Habits Questionnaire (CSHQ) Score during treatment.	4-week; 8-week
Change from baseline on spectral power in the alpha, theta, and gamma frequencies as measured by electroencephalogram (EEG) during treatment.	4-week; 8-week
Change from baseline in parent rated Social Responsiveness Scale, Second Edition (SRS-2) Social Avoidance Factor Score during treatment.	4-week; 8-week
Change from baseline in parent rated Social Responsiveness Scale, Second Edition (SRS-2) Emotion Recognition Factor Score during treatment.	4-week; 8-week
Change from baseline in parent rated Social Responsiveness Scale, Second Edition (SRS-2) Interpersonal Relatedness Factor Score during treatment.	4-week; 8-week
Change from baseline in parent rated Social Responsiveness Scale, Second Edition (SRS-2) Insistence On Sameness Factor Score during treatment.	4-week; 8-week
Change from baseline in parent rated Social Responsiveness Scale, Second Edition (SRS-2) Repetitive Mannerisms Factor Score during treatment.	4-week; 8-week
Change from baseline in parent rated Social Responsiveness Scale, Second Edition (SRS-2) Attachment and Affiliation Factor Score during treatment.	4-week; 8-week
Change from baseline in parent rated Social Responsiveness Scale, Second Edition (SRS-2) Non-facial Communication Production Factor Score during treatment.	4-week; 8-week
Change from baseline in parent rated Social Responsiveness Scale, Second Edition (SRS-2) Facial Communication Production Factor Score during treatment.	4-week; 8-week
Change from baseline in parent rated Social Responsiveness Scale, Second Edition (SRS-2) Mental States Understanding Factor Score during treatment.	4-week; 8-week

Collaborators and Investigators

• Sponsor: Stanford University
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Investigators: Principal Investigator: Antonio Y. Hardan, M.D., Stanford University; Principal Investigator: Karen J. Parker, Ph.D., Stanford University

Study record dates

Study Major Dates

• Study Start (Actual): February 20, 2018
• Primary Completion (Actual): March 18, 2024
• Study Completion (Actual): March 18, 2024

Study Registration Dates

• First Submitted: June 28, 2017
• First Submitted That Met QC Criteria: June 28, 2017
• First Posted (Actual): July 2, 2017

Study Record Updates

• Last Update Posted (Actual): March 21, 2024
• Last Update Submitted That Met QC Criteria: March 19, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Autism; Autism Spectrum Disorder (ASD)
• Additional Relevant MeSH Terms: Mental Disorders; Neurodevelopmental Disorders; Child Development Disorders, Pervasive; Autistic Disorder; Autism Spectrum Disorder; Physiological Effects of Drugs; Natriuretic Agents; Hemostatics; Coagulants; Vasoconstrictor Agents; Antidiuretic Agents; Vasopressins; Arginine Vasopressin
• Other Study ID Numbers: IRB-39972; 1R01HD091972 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: National Database for Autism Research (NDAR) Submission per NIH requirements

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No