The University of Southampton
University of Southampton Institutional Repository

A phase II randomized, double-blind, placebo-controlled study of the efficacy, safety, and tolerability of arbaclofen administered for the treatment of social function in children and adolescents with Autism Spectrum Disorders: study protocol for AIMS-2-TRIALS-CT1

A phase II randomized, double-blind, placebo-controlled study of the efficacy, safety, and tolerability of arbaclofen administered for the treatment of social function in children and adolescents with Autism Spectrum Disorders: study protocol for AIMS-2-TRIALS-CT1
A phase II randomized, double-blind, placebo-controlled study of the efficacy, safety, and tolerability of arbaclofen administered for the treatment of social function in children and adolescents with Autism Spectrum Disorders: study protocol for AIMS-2-TRIALS-CT1

Background: Autism Spectrum Disorder (ASD or autism) is characterized by difficulties in social communication and interaction, which negatively impact on individuals and their families' quality of life. Currently no pharmacological interventions have been shown to be effective for improving social communication in autism. Previous trials have indicated the potential of arbaclofen for improving social function among autistic children and adolescents with fluent speech. The AIMS2TRIALS-Clinical Trial 1 (AIMS-CT1) will examine whether arbaclofen is superior to placebo in improving social function and other secondary outcomes over 16 weeks, along with safety and tolerability profiles.

Methods: AIMS-CT1 is an international, multi-site, double-blind, parallel group Phase II randomized clinical trial. It will include 130 males and females aged 5:0-17:11 years, with a diagnosis of ASD and fluent speech. Eligible participants will be randomized on a ratio of 1:1 for a 16-week treatment period. Medication will be titrated over 5 weeks. The primary outcome is the effect on social function from weeks 0 to 16 measured on the Socialization domain of the Vineland Adaptive Behavior Scales, 3rd editionTM. Secondary outcome measures include the CGI-S (Clinical Global Impression-Severity), CGI-I (Clinical Global Impression-Improvement), other areas of adaptive function, social communication and other autism symptoms, co-occurring behavior problems and health-related quality of life. Genetic and electrophysiological markers will be examined as potential stratifiers for treatment response. Exploratory novel digital technologies will also be used to measure change, examining simultaneously the validity of digital biomarkers in natural environments. The safety and tolerability of the drug will also be examined. Our protocol is very closely aligned with a parallel Canadian trial of 90 participants (ARBA Study, US NCT number: NCT03887676) to allow for secondary combined analyses. Outcomes will be compared using both an Intent-to-reat and Per Protocol approach.

Discussion: the outcomes of this trial, combined with the parallel Canadian trial, will contribute to the evidence base for medications used to help social difficulties among young autistic individuals; demonstrate the capabilities of the AIMS-2-TRIALS network of academic centers to deliver clinical trials; and support future drug development.

Clinical Trial Registration: EudraCT number: 2018-000942-21 and ClinicalTrials.gov registry number: NCT03682978. Currently under protocol v.7.2, dated 20.11.2020.

1664-0640
Parellada, Mara
87b7cfbb-bb38-4b6b-bc8d-ec8dd8c07a14
San José Cáceres, Antonia
17a1afd8-0f9b-4dad-a4b3-29b18e5fab07
Palmer, Melanie
1c1e67ed-10f4-48a9-9d48-509e82f3e94a
Delorme, Richard
455473a3-f39d-44c3-957a-e98d017a8e60
Jones, Emily J.H.
61b2a07d-52d7-4e70-acfa-5afc0f05a711
Parr, Jeremy R.
027cbe53-7f34-4ead-8b5a-14aa72a23204
Anagnostou, Evdokia
0ac63197-3024-4992-99ec-7a55012f8e02
Murphy, Declan G.M.
dca7800f-7da1-451f-8cb5-55e48de738a2
Loth, Eva
b3f3f410-6ff9-433c-b5a0-8852ec5d2d01
Wang, Paul P.
3d345fe1-4cfa-4ee8-bd88-fe2d286c0dc1
Charman, Tony
97323a9f-7557-4e52-a456-0aa0b1d4661f
Strydom, Andre
3fb4df2a-3ac1-4783-9309-628b770e0e46
Arango, Celso
cb8bc78e-3bde-4e01-b377-2c893d6c272b
Parlatini, Valeria
6cdfb200-40ce-43ce-84da-dcb6eba0f67a
et al.
Parellada, Mara
87b7cfbb-bb38-4b6b-bc8d-ec8dd8c07a14
San José Cáceres, Antonia
17a1afd8-0f9b-4dad-a4b3-29b18e5fab07
Palmer, Melanie
1c1e67ed-10f4-48a9-9d48-509e82f3e94a
Delorme, Richard
455473a3-f39d-44c3-957a-e98d017a8e60
Jones, Emily J.H.
61b2a07d-52d7-4e70-acfa-5afc0f05a711
Parr, Jeremy R.
027cbe53-7f34-4ead-8b5a-14aa72a23204
Anagnostou, Evdokia
0ac63197-3024-4992-99ec-7a55012f8e02
Murphy, Declan G.M.
dca7800f-7da1-451f-8cb5-55e48de738a2
Loth, Eva
b3f3f410-6ff9-433c-b5a0-8852ec5d2d01
Wang, Paul P.
3d345fe1-4cfa-4ee8-bd88-fe2d286c0dc1
Charman, Tony
97323a9f-7557-4e52-a456-0aa0b1d4661f
Strydom, Andre
3fb4df2a-3ac1-4783-9309-628b770e0e46
Arango, Celso
cb8bc78e-3bde-4e01-b377-2c893d6c272b
Parlatini, Valeria
6cdfb200-40ce-43ce-84da-dcb6eba0f67a

Parellada, Mara, San José Cáceres, Antonia and Palmer, Melanie , et al. (2021) A phase II randomized, double-blind, placebo-controlled study of the efficacy, safety, and tolerability of arbaclofen administered for the treatment of social function in children and adolescents with Autism Spectrum Disorders: study protocol for AIMS-2-TRIALS-CT1. Frontiers in Psychiatry, 12, [701729]. (doi:10.3389/fpsyt.2021.701729).

Record type: Article

Abstract

Background: Autism Spectrum Disorder (ASD or autism) is characterized by difficulties in social communication and interaction, which negatively impact on individuals and their families' quality of life. Currently no pharmacological interventions have been shown to be effective for improving social communication in autism. Previous trials have indicated the potential of arbaclofen for improving social function among autistic children and adolescents with fluent speech. The AIMS2TRIALS-Clinical Trial 1 (AIMS-CT1) will examine whether arbaclofen is superior to placebo in improving social function and other secondary outcomes over 16 weeks, along with safety and tolerability profiles.

Methods: AIMS-CT1 is an international, multi-site, double-blind, parallel group Phase II randomized clinical trial. It will include 130 males and females aged 5:0-17:11 years, with a diagnosis of ASD and fluent speech. Eligible participants will be randomized on a ratio of 1:1 for a 16-week treatment period. Medication will be titrated over 5 weeks. The primary outcome is the effect on social function from weeks 0 to 16 measured on the Socialization domain of the Vineland Adaptive Behavior Scales, 3rd editionTM. Secondary outcome measures include the CGI-S (Clinical Global Impression-Severity), CGI-I (Clinical Global Impression-Improvement), other areas of adaptive function, social communication and other autism symptoms, co-occurring behavior problems and health-related quality of life. Genetic and electrophysiological markers will be examined as potential stratifiers for treatment response. Exploratory novel digital technologies will also be used to measure change, examining simultaneously the validity of digital biomarkers in natural environments. The safety and tolerability of the drug will also be examined. Our protocol is very closely aligned with a parallel Canadian trial of 90 participants (ARBA Study, US NCT number: NCT03887676) to allow for secondary combined analyses. Outcomes will be compared using both an Intent-to-reat and Per Protocol approach.

Discussion: the outcomes of this trial, combined with the parallel Canadian trial, will contribute to the evidence base for medications used to help social difficulties among young autistic individuals; demonstrate the capabilities of the AIMS-2-TRIALS network of academic centers to deliver clinical trials; and support future drug development.

Clinical Trial Registration: EudraCT number: 2018-000942-21 and ClinicalTrials.gov registry number: NCT03682978. Currently under protocol v.7.2, dated 20.11.2020.

Text
fpsyt-12-701729 - Version of Record
Available under License Creative Commons Attribution.
Download (1MB)

More information

Accepted/In Press date: 17 June 2021
Published date: 24 August 2021

Identifiers

Local EPrints ID: 488837
URI: http://eprints.soton.ac.uk/id/eprint/488837
ISSN: 1664-0640
PURE UUID: c29fb7e1-8b45-4a89-b809-bd844bc7605d
ORCID for Valeria Parlatini: ORCID iD orcid.org/0000-0002-4754-2494

Catalogue record

Date deposited: 08 Apr 2024 16:35
Last modified: 10 Sep 2024 02:09

Export record

Altmetrics

Contributors

Author: Mara Parellada
Author: Antonia San José Cáceres
Author: Melanie Palmer
Author: Richard Delorme
Author: Emily J.H. Jones
Author: Jeremy R. Parr
Author: Evdokia Anagnostou
Author: Declan G.M. Murphy
Author: Eva Loth
Author: Paul P. Wang
Author: Tony Charman
Author: Andre Strydom
Author: Celso Arango
Author: Valeria Parlatini ORCID iD
Corporate Author: et al.

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×