Intranasal Vasopressin Treatment in Children With Autism

Phase 2

Completed

Conditions: Autism
Autism Spectrum Disorder
ASD

Interventions: Drug: Vasopressin (USP) Injectable Solution [Vasostrict]
Drug: Placebo

Registration Number: NCT03204786

Lead Sponsor: Stanford University

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 157

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo-Vasopressin	Vasopressin (USP) Injectable Solution [Vasostrict]	4 weeks of placebo nasal spray followed by 4 weeks of vasopressin nasal spray (16 international units twice daily)
Placebo-Vasopressin	Placebo	4 weeks of placebo nasal spray followed by 4 weeks of vasopressin nasal spray (16 international units twice daily)
Placebo-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)
Vasopressin-Vasopressin	Vasopressin (USP) Injectable Solution [Vasostrict]	8 weeks of vasopressin nasal spray (16 international units twice daily)
Placebo-Placebo	Vasopressin (USP) Injectable Solution [Vasostrict]	8 weeks of placebo nasal spray; followed by a 4 week open-label extension of vasopressin nasal spray (16 international units twice daily)

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Parent Rated Social Responsiveness Scale, Second Edition (SRS-2) Total Scores During Treatment.	baseline, 4-week, 8-week	Social Responsiveness Scale, 2nd Edition (SRS) scores measure social abilities with lower scores meaning better social abilities. The SRS-2 is reported as a total score (T-Score Range: 37 to above 90), and the Diagnostic and Statistical Manual of Mental Disorders (DSM)-5-compatible Social Communication and Interaction (SCI) score (T-Score Range: 36 to above 90) and Restricted Interests and Repetitive Behavior (RRB) score (T-Score range: 41 to above 90). A T-score of 50 indicates the population mean with a standard deviation of 10. Higher scores correspond to greater symptom levels (≤ 59: within normal limits; 60-65: mild range; 66-75: moderate range; ≥ 76: severe range). Change is reported as 4-week minus the baseline score, and 8-week minus the 4-week score. For this outcome, the baseline score is the average of the screening visit and baseline visit (average approximately 2 to 3 weeks after the screening visit).

Secondary Outcome Measures

Name	Time	Method
Baseline Vasopressin Concentration Predicting Primary and Secondary Behavioral Outcome Measures.	4-week; 8-week
Change From Baseline in Clinical Global Impression (CGI) Scores During Treatment.	baseline; 4-week; 8-week	Clinician assessment of CGI severity (CGI-S) and CGI improvement (CGI-I) scores. * Higher scores on the CGI-S mean greater social and communication deficits (range: 1 to 7). * Lower scores on the CGI-I correspond to greater improvement in the areas assessed in the CGI-S, and higher scores correspond to worsening (range: 1 to 7). There is no baseline score for the CGI-I, it represents the clinician's subjective assessment of change.
Change From Baseline on Reading the Mind in the Eyes Test (RMET) During Treatment.	baseline; 4-week; 8-week	Score range: 0 to 28; higher scores mean better ability to read emotions and lower scores mean worse ability to read emotions.
Change From Baseline on the Facial Emotion Recognition Test During Treatment.	baseline; 4-week; 8-week	Score range: 0 to 42; higher scores mean better facial emotion recognition abilities. Lower scores mean worse facial emotion recognition abilities.
Change From Baseline in Parent Rated Repetitive Behavior Scale Revised (RBS-R) Scores During Treatment.	baseline; 4-week; 8-week	Score range: 0 to 129; higher scores on the RBS-R mean higher levels of repetitive and restricted behaviors.
Change From Baseline in Parent Rated Spence Children's Anxiety Scale (SCAS) During Treatment.	baseline; 4-week; 8-week	Scale measuring severity of anxiety symptoms. Score range: 0 to 114; higher scores mean higher levels of anxiety, lower scores mean lower levels of anxiety.
Change From Baseline on Electrocardiogram (EKG) P Duration During Treatment.	baseline to 4-week, 8-week, and 12-week
Change From Baseline on Electrocardiogram (EKG) PR Interval During Treatment.	baseline to 4-week, 8-week, and 12-week
Adverse Event Severity	Up to 12 weeks	Adverse events collated according to intensity for each pre-allocated treatment group.
Change From Baseline on Electrocardiogram (EKG) QRS Interval During Treatment.	baseline to 4-week, 8-week, and 12-week
Change From Baseline on Electrocardiogram (EKG) QT Interval During Treatment.	baseline to 4-week, 8-week, and 12-week
Change From Baseline on Blood Clinical Labs (Sodium) During Treatment.	baseline to 4-week, 8-week, and 12-week
Change From Baseline on Blood Clinical Labs (Potassium) During Treatment.	baseline to 4-week, 8-week, and 12-week
Change From Baseline on Blood Clinical Labs (Chloride) During Treatment.	baseline to 4-week, 8-week, and 12-week	Change from baseline on blood clinical labs (Chloride) during treatment.
Change From Baseline on Blood Clinical Labs (CO2) During Treatment.	baseline to 4-week, 8-week, and 12-week
Change From Baseline on Blood Clinical Labs (Anion Gap) During Treatment.	baseline to 4-week, 8-week, and 12-week
Change From Baseline on Blood Clinical Labs (Glucose) During Treatment.	baseline to 4-week, 8-week, and 12-week
Change From Baseline on Blood Clinical Labs (Creatinine) During Treatment.	baseline to 4-week, 8-week, and 12-week
Change From Baseline on Blood Clinical Labs (Urea Nitrogen) During Treatment.	baseline to 4-week, 8-week, and 12-week
Change From Baseline on Blood Clinical Labs (Calcium) During Treatment.	baseline to 4-week, 8-week, and 12-week
Change From Baseline on Blood Clinical Labs (Osmolality) During Treatment.	baseline to 4-week, 8-week, and 12-week
Change From Baseline on Urine Clinical Labs (Osmolality) During Treatment.	baseline to 4-week, 8-week, and 12-week
Change From Baseline on Vital Signs (Systolic Blood Pressure) During Treatment.	Up to 12 weeks
Change From Baseline on Vital Signs (Diastolic Blood Pressure) During Treatment.	Up to 12 weeks
Change From Baseline on Vital Signs (Pulse) During Treatment.	Up to 12 weeks
Change From Baseline on Height During Treatment.	baseline to 4-week, 8-week, and 12-week
Change From Baseline on Weight During Treatment.	baseline to 4-week, 8-week, and 12-week
Change From Baseline on the Dosage Record Treatment Emergent Symptom Scale (DOTES) During Treatment.	Up to 12 weeks	The DOTES evaluates a subset of symptoms related to various medical conditions. The clinician assesses intensity (0=Not assessed, 1=Not present, 2=Mild, 3=Moderate, 4=Severe), relatedness (0=None, 1=Remote, 2=Possible, 3=Probable, 4=Defined), and action taken (0=None, 1=Increased , 2=Contractive Rx, 3=Change Dose, 4=Change Dose Plus Contractive Rx, 5=Suspend Rx, 6=Discontinue Rx). Side effects are included that have increased in severity, become more likely to be related, or require action. Change from baseline is reported as the number of participants with change in these side effects during treatment.
Change From Baseline in Overt Aggression Scale (OAS) During Treatment.	2-week, 4-week; 6-week, 8-week