A randomized placebo-controlled pilot trial shows that intranasal vasopressin improves social deficits in children with autism

Abstract

The social impairments of autism spectrum disorder (ASD) have a major impact on quality of life, yet there are no medications that effectively treat these core social behavior deficits. Preclinical research suggests that arginine vasopressin (AVP), a neuropeptide involved in promoting mammalian social behaviors, may be a possible treatment for ASD. Using a double-blind, randomized, placebo-controlled, parallel study design, we tested the efficacy and tolerability of a 4-week intranasal AVP daily treatment in 30 children with ASD. AVP-treated participants aged 6 to 9.5 years received the maximum daily target dose of 24 International Units (IU); participants aged 9.6 to 12.9 years received the maximum daily target dose of 32 IU. Intranasal AVP treatment compared to placebo enhanced social abilities as assessed by change from baseline in this phase 2 trial's primary outcome measure, the Social Responsiveness Scale, 2nd Edition total score (SRS-2 T score; F _1,20 = 9.853; P = 0.0052; η_p ² = 33.0%; Cohen's d = 1.40). AVP treatment also diminished anxiety symptoms and some repetitive behaviors. Most of these findings were more pronounced when we accounted for pretreatment AVP concentrations in blood. AVP was well tolerated with minimal side effects. No AVP-treated participants dropped out of the trial, and there were no differences in the rate of adverse events reported between treatment conditions. Last, no changes from baseline were observed in vital signs, electrocardiogram tracings, height and body weight, or clinical chemistry measurements after 4 weeks of AVP treatment. These preliminary findings suggest that AVP has potential for treating social impairments in children with ASD.

Fig. 1.. The CONSORT flow diagram for the phase 2 clinical trial.

The CONSORT flow diagram details the progress, from screening through to study completion, of participants in the double-blind randomized placebo-controlled trial testing a 4-week intranasal vasopressin treatment versus placebo in children with ASD. A total of 149 prospective participants were screened. Thirty-eight of the 68 individuals enrolled in the study were not randomized owing to either not meeting eligibility criteria or declining to participate. All 30 participants who were randomized to a treatment condition or placebo completed the study, independent of whether they were in the vasopressin or placebo group.

Fig. 2.. Improvement scores for participants receiving 4-week intranasal arginine vasopressin (AVP) treatment versus placebo.

Participants’ improvement scores for the clinical trial’s key primary and secondary outcome measures are provided for each treatment condition. (A) Primary outcome measure: the Social Responsiveness Scale, 2nd Edition (SRS-2) T score. (B to F) Secondary outcome measures: Clinical Global Impression (CGI)-Improvement score (B), Reading the Mind in the Eyes Test (RMET) score (C), Facial Emotion Recognition Test (FERT) score (D), Spence Children’s Anxiety Scale (SCAS) score (E), and Repetitive Behaviors Scale-Revised (RBS-R) total score (F). General linear model F tests were used to evaluate whether participants treated with AVP (orange circles) versus placebo (blue circles) differed as a main effect of treatment (i.e., at the mean pretreatment blood AVP concentration). Data are presented as least-squares means (LSM)±SEM, with individual data points plotted as residuals from their LSM adjacent to the respective error bar. Thus, all data are plotted corrected for other variables in the analysis. Data depicted in (A) and (C) to (F) are presented as absolute difference scores (between posttreatment and baseline pretreatment) such that positive numbers on the y axis indicate improvement. Data depicted in (B) are presented as clinician improvement ratings where 1 = very much improved since the initiation of treatment, 2 = much improved, 3 = minimally improved, and 4 = no change since the initiation of treatment. AVP-treated participants differed significantly from placebo-treated participants in their improvement scores on nearly all measures except for the RBS-R, in which there was no overall group difference. n = 30 for the SRS, CGI, and SCAS; n = 29 for the RBS-R; n = 17 for the FERT; and n = 16 for the RMET.