A Single Dose, Randomized, Controlled Proof-Of-Mechanism Study of a Novel Vasopressin 1a Receptor Antagonist (RG7713) in High-Functioning Adults with Autism Spectrum Disorder

Daniel Umbricht, Marta del Valle Rubido, Eric Hollander, James T. McCracken, Frederick Shic, Lawrence Scahill, Jana Noeldeke, Lauren Boak, Omar Khwaja, Lisa Squassante, Christophe Grundschober, Heidemarie Kletzl, Paulo Fontoura

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

The core symptoms of autism spectrum disorder (ASD) include impaired social communication, repetitive behaviors, and restricted interests. No effective pharmacotherapy for these core deficits exists. Within the domain of social communication, the vasopressin system is implicated in social cognition and social signaling deficits of ASD, and represents a potential therapeutic target. We assessed the effects of a single 20 mg intravenous dose of the arginine vasopressin receptor 1A (V1a) antagonist, RG7713, on exploratory biomarkers (eye tracking), behavioral and clinical measures of social cognition and communication (affective speech recognition (ASR), reading the mind in the eyes, olfactory identification, scripted interaction), and safety and tolerability in a multicenter, randomized, double-blind, placebo-controlled, cross-over study of 19 high-functioning adult male subjects with DSM-IV Autistic Disorder (age 18–45 years; full scale IQ >70; ABC-Irritability subscale ⩽13). Eye-tracking showed an increase in biological motion orienting preference with RG7713 (ES=0.8, p=0.047) and a non-significant improvement in the composite score (ES=0.2, p=0.29). RG7713 reduced ability to detect lust (ES=−0.8, p=0.03) and fear (ES=−0.7, p=0.07) in ASR. However, when all eight individual emotion subscales were combined into an overall ASR performance score, the reduction was non-significant (ES=−0.1, p=0.59). Thirteen adverse events were reported in 10 subjects; all were of mild (11/13) or moderate (2/13) severity. Although interpretation should be cautious due to multiple comparisons and small sample size, these results provide preliminary evidence from experimental and behavioral biomarkers, that blockade of the V1a receptor may improve social communication in adults with high-functioning ASD. ClinicalTrials.gov identifier: NCT01474278 A Study of RO5028442 in Adult Male High-Functioning Autistic Patients. Available at: https://clinicaltrials.gov/ct2/show/NCT01474278Neuropsychopharmacology advance online publication, 16 November 2016; doi:10.1038/npp.2016.232.

Original languageEnglish (US)
JournalNeuropsychopharmacology
DOIs
StateAccepted/In press - Nov 16 2016

Fingerprint

Communication
Vasopressin Receptors
Cognition
Biomarkers
Aptitude
Autistic Disorder
Vasopressins
Diagnostic and Statistical Manual of Mental Disorders
Sample Size
Cross-Over Studies
Fear
Publications
Reading
Emotions
Placebos
Safety
Drug Therapy
Autism Spectrum Disorder
Antidiuretic Hormone Receptor Antagonists
Recognition (Psychology)

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

Cite this

A Single Dose, Randomized, Controlled Proof-Of-Mechanism Study of a Novel Vasopressin 1a Receptor Antagonist (RG7713) in High-Functioning Adults with Autism Spectrum Disorder. / Umbricht, Daniel; del Valle Rubido, Marta; Hollander, Eric; McCracken, James T.; Shic, Frederick; Scahill, Lawrence; Noeldeke, Jana; Boak, Lauren; Khwaja, Omar; Squassante, Lisa; Grundschober, Christophe; Kletzl, Heidemarie; Fontoura, Paulo.

In: Neuropsychopharmacology, 16.11.2016.

Research output: Contribution to journalArticle

Umbricht, D, del Valle Rubido, M, Hollander, E, McCracken, JT, Shic, F, Scahill, L, Noeldeke, J, Boak, L, Khwaja, O, Squassante, L, Grundschober, C, Kletzl, H & Fontoura, P 2016, 'A Single Dose, Randomized, Controlled Proof-Of-Mechanism Study of a Novel Vasopressin 1a Receptor Antagonist (RG7713) in High-Functioning Adults with Autism Spectrum Disorder', Neuropsychopharmacology. https://doi.org/10.1038/npp.2016.232
Umbricht, Daniel ; del Valle Rubido, Marta ; Hollander, Eric ; McCracken, James T. ; Shic, Frederick ; Scahill, Lawrence ; Noeldeke, Jana ; Boak, Lauren ; Khwaja, Omar ; Squassante, Lisa ; Grundschober, Christophe ; Kletzl, Heidemarie ; Fontoura, Paulo. / A Single Dose, Randomized, Controlled Proof-Of-Mechanism Study of a Novel Vasopressin 1a Receptor Antagonist (RG7713) in High-Functioning Adults with Autism Spectrum Disorder. In: Neuropsychopharmacology. 2016.
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