Clinical and Biomarker Effects of a Novel Vasopressin 1a Receptor Antagonist Vs Placebo in High Functioning Adult Autism

Background:  

Oxytocin and vasopressin play a critical role in social cognition and social signalling deficits of ASD.  Experimental therapeutic interventions to enhance oxytocin or block Va1A receptor signalling may modulate these domains in ASD

Objectives:  

To explore the impact of a novel V1a antagonist R050288442 vs placebo on core social cognition measures, exploratory biomarkers, and safety/tolerability measures in adult high functioning ASD.

Methods:  

High-functioning adults (M=23.4 years, range=18 to 40 years) with autism (n=19) participated in a multi-center (3-site), randomized, double-blind, placebo-controlled, cross-over study of the effects of novel vasopressin 1a receptor antagonist R050288442 . Each participant was seen on two separate days (1 week apart) for dosing a 2 hour infusion of  R050288442 or placebo.  Safety/tolerability, PK, PD, core social cognition, olfaction, language sampling and AVPR1A polymorphisms measures were collected. 

Results:  

At baseline, the Affective Speech Recognition (ASR), Reading the Mind in the Eyes (RMET)  and olfaction measures correlated with measures of functioning on the Vineland and ADOS as well as IQ.  The Va1 antagonist showed evidence of anxiolysis.  The Va1 antagonist showed effects on olfaction, RMET and scripted interaction in the predicted direction of modest effect sizes.  There were large negative effect sizes of the Va1a antagonist vs placebo on the social cognition ASR measure Lust and Fearful subscales, and there appeared to be carryover effects from infusion 1 to infusion 2 that may influence these findings.

Conclusions:  

This study provides preliminary evidence of the ability of a novel V1a antagonist R050288442 to affect core symptoms of social cognition and olfaction.  Effects on the laying down of social memory and social learning may persist well past the pharmacokinetic effects of the compound. These results should be taken as preliminary but may help to guide the development of new oral vasopressin antagonist interventions in ASD.