Research ArticleAutism Spectrum Disorder

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

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Science Translational Medicine  08 May 2019:
Vol. 11, Issue 491, eaau7356
DOI: 10.1126/scitranslmed.aau7356

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Modulating vasopressin in ASD

The neuropeptide vasopressin has been implicated in the regulation of social behaviors in animals and humans. The VANILLA clinical trial evaluated balovaptan, an oral selective vasopressin V1a receptor antagonist, in 223 men with autism spectrum disorder (ASD). This 12-week phase 2 trial showed no improvement on the primary endpoint (SRS-2 score) but did show improvement on the secondary outcome measure of adaptive behaviors assessed by the Vineland-II scale (Bolognani et al.). In a related clinical study involving a 4-week intranasal administration of vasopressin to children with ASD, improvements were observed on the SRS-2 primary outcome measure (Parker et al.). Both drugs were well tolerated and had an acceptable safety profile, suggesting that modulating the vasopressin pathway may be a useful therapeutic strategy for ASD.

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; F1,20 = 9.853; P = 0.0052; ηp2 = 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.

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