Autism Clinical Trials in Western Australia: ACT for children with an

Autism Clinical Trials in Western Australia:
ACT for children with an Autism Spectrum
Disorder (ASD)
Jo Granich
Clinical Trials Coordinator
Worldwide Universities Network (WUN): Autism Conference
“Autism: Global Challenges and Local Needs”
16-17 January, 2014
Outline
• What is Autism?
• Autism Research and Clinical trials…where do we stand?
– Our Mission and Research Aims
– CRC for Living with Autism
• RCT- essentials
• Our Clinical Trials
– Fluoxetine
– Oxytocin
– TOBY Playpad – an iPad App
– Fish Oil Supplementation
• More trials…
• Trial Challenges
• Conclusion
Overview of Autism
• What is Autism?
– 1% population
•
More than combined number of children with cerebral palsy,
diabetes, deafness, blindness and leukaemia.
Symptoms vary in severity
Repetitive
Behaviours
Highly heritable condition
No ‘cure’ and no standard Tx
Often presents with many other difficulties &
co-morbidities e.g., ADHD, ID, sleep or GIT problems
Effects on family are significant
–
–
–
–
–
•
e.g., highest parental divorce of any childhood condition
Social
Difficulties
Deficits in
Communication
Autism research and clinical trials
Autism research funding allocated in US, 1997-2006
Translational
20%
15%
Basic Research
Clinical
Singh et al., 2009, J Autism & Dev Disorders
Our Autism Research Team
Group Leader:
Professor Andrew Whitehouse
Clinical Trials Coordinator:
Jo Granich
Research Coordinators:
Anna Hunt; Alena Dass; Alexis Rene;
Suzanne Meldrum
Laboratory/Research Officer:
Blagica Penova-Veselinovic
PhD Students: 7
Honours Students: 2
Our Mission
1.
1st Research Aim
To identify the causes of autism and related conditions:
 Western Australian Autism Biological Registry (WAABR)
 Ongoing Cross-sectional Study
 Collects Phenotypic and genotypic information on
ASD diagnosed individuals (2-17 year olds), and their
families.
 PRegnancy Investigation of Siblings & Mothers (PRISM) of Children with
Autism
 Prospective Case Control, Longitudinal Study
 To identify prenatal biomarkers that might be associated with autism:
•
•
Testosterone concentrations in-utero & in umbilical cord blood
Head growth in-utero & early post-natal life
Our Mission
2nd Research Aim
2. Find out ways to help individuals with autism live the most fulfilling life
possible.
$ Funding Journey $
Cooperative Research Centre for Autism
• CRC Living with Autism - first national cooperative research effort focused
on Autism – “whole-of-life” approach
• Unique mix of partners - 56 participants (12 core partners) including
Australian Government, NFP Service Providers, Universities, Researchers,
NFP community organisations & businesses.
• $31 million (Aus$) for 8 years from Commonwealth and in-kind
contributions of $63 million from industry = $104 million program.
• CRC – critical mass aims to bridge fundamental research with getting
things done and applying it for the benefits of all Australians.
Cooperative Research Centre for
Living with Autism Spectrum Disorders (Autism CRC)
Three Core Research Programs
Research Program 1 – DIAGNOSIS: A better start through early diagnosis
This program aims to harness existing knowledge of ASD to improve diagnosis, and use breakthroughs
in biological research to identify subtypes of ASD and the most effective interventions for these.
To do this we will create one of the largest repositories of autistic biological information in the world,
that will enable us to:
•Identify factors that may lead to autism;
•Revolutionise diagnostic accuracy; and
•Help match children with the intervention that works best for their biological make-up.
Professor Andrew Whitehouse is the Director of Program 1.
http://www.autismcrc.com.au/
Three Core Research Programs
Research Program 2 – EDUCATION: Enhancing teaching and learning
This program aims to research the provision of ASD appropriate educational environments and
programs that optimise students’ social, behavioural and academic success, and equip
teachers to manage even the most complex behaviours.
Professor Suzanne Carrington is the Director of Program 2.
http://www.autismcrc.com.au/
Three Core Research Programs
Research Program 3 – ADULTHOOD: Finding a place in society
This program aims to improve opportunities for people with ASD to successfully
participate in higher education and employment, and identify best practice in physical
and mental health management.
Professor Torbjorn Falkmer is the Director of Program 3.
http://www.autismcrc.com.au/
Randomised Controlled Trials (RCT)
• Epidemiological design - high quality data
• Gold standard research
• Treatment randomly allocated
• Efficacy of a treatment
• Evaluate therapeutic effect vs side-effects = evidence!
Autism Clinical Trials @ The
Telethon Institute for Child Health Research
Fluoxetine for Autistic Behaviours – The FAB Trial
• Multi-site (WA, Vic & NSW) randomised controlled trial
vs.
Fluoxetine
Placebo
• For the tx of RRS behaviours causing functional impairment in
7-17 year olds with autism
• AIM
efficacy & safety of Fluoxetine (oral syrup)
• Rationale
evidence for the use of Fluoxetine (SSRIs) for RRS is
currently limited & inconclusive 
FAB Trial Study Design
Final
Assessment
Post-Medication
Assessments
Screening
Criteria
Pre-Trial
Assessments
Fluoxetine
Participants
Weaning
FFU
Randomisation
Placebo
• Double-blind
• Placebo controlled
1-16 week
Treatment Period
Weaning
17-20 week
FFU
22 week
Off Medication Period
• Parallel group design
FFU: Final Follow Up
Assessments and Outcome Measures
• Medical History
• Physical Examination
Primary
• Children’s Yale-Brown Obsessive
Compulsion Scale – Modified for
Pervasive Developmental Disorders
(CYBOCS-PDD)
Secondary
• Cheek Brush Test
• IQ Test
• ADI - R
• Repetitive Behaviour Scale – Revised (RBS-R)
• Spence Children’s Anxiety Scale (SCAC)
• Aberrant Behaviour Checklist (ABC) –
Community Version
• Clinical Global Impressions Scale (CGI) –
Global Improvement and Efficacy Index
Compliance1, Tolerance and Checklists2 = Safety
1. Medication Diaries
2a. A 51-point side effects checklist
2b. Global Improvement and Efficacy
Index: The CGI
+
During Treatment and Weaning off Medication Period
Oxytocin nasal spray for young children with autism:
OT Trial
• Multi-site (NSW & WA) randomised double-blind placebo-controlled trial.
• ASD
social communication problems
poor social functioning.
So, why OT and how ?
 +ve role of OT (hormone) in modulation of social recognition & behaviour.
  OT plasma levels in children with ASD.
AIM
efficacy of 12-wk Tx of OT nasal spray in 3-6 year olds (n=100) with ASD &
Id key biomarkers of response.
Oxytocin Trial Protocol
Pre-Screening
•
•
Inclusion/exclusion criteria
Informed Consent
Baseline Medical
Diagnostic & Cognitive
Assessments (1)
•
•
•
•
Medical History
Practice (Saline) Spray for 3wks
Saliva and Blood samples
LIPS & ADOS
Behavioural Assessments
(2)
•
•
•
•
Randomisation
OT (Syntocinon 12IU) or Placebo Tx Pack – 12 wks
Saliva and Blood samples
ADOS plus other behavioural, social/cognition measures*
Behavioural Assessments
(3)
Follow Up 1 @ end of 3 mths
•
•
•
OT or Placebo Tx Ceases
Saliva and Blood samples
Repeat of ADOS and social/cognition assessments
Behavioural Assessments
(4)
Follow Up 2 @ end of 6 mths
•
•
•
Saliva and Blood samples
Repeat of ADOS and social/cognition assessments
Debrief and Trial completion
* SRS, DBC, RBS-R, CGI, CSQ, SMI iView X Red
TOBY Playpad Trial
 Multi-site (Western Australia & Victoria) randomised single-blind trial
 TOBY (Therapy Outcomes By You) – an iPad based App delivering early
intervention (EI) curriculum in the family home
http://www.youtube.com/embed/-mYzqWGB1lU?autoplay=1
 Evidence
with ASD
intense and sustained EI
 EI = $$$ and waiting list
=  window of opportunity
outcomes for children
families unable to access EI
 TOBY can improve time & cost-effectiveness of EI
TOBY Playpad Trial
Aims:
1.To determine if the TOBY App is effective in improving children with
ASD learn key pre-requisite skills required for communication, language
and cognitive development.
2. To evaluate if the TOBY App empowers parents to deliver therapy for
their child.
Study Participants:
Children under 4 years
Diagnosed with ASD in the last 6 months
TOBY Playpad Trial: Study Design
1st Follow up
Assessments
Pre-Trial
Assessments
Screening
Criteria
Participants
2nd Follow up
Assessments
TOBY App
Group
TOBY App
Group
Comparison
Group
Comparison
Group
Randomisation
Measures:
x12 parent questionnaires
x3 child play-based /early learning
assessments
X2 Therapy diaries
TOBY Reports
1 st Phase
2nd Phase
0- 3 months
3- 6 months
The Fish Oil for Autism Intervention Study - The FAIS study
 A randomised double-blind placebo-controlled trial of high-dose fish oil
supplementation for children (n=50) with ASD led by Dr Suzanne Meldrum
 Essential Fatty Acids (EFA): LCPUFA – docosahexaenoic acid (DHA) &
eicosapentaenoic acid (EPA) significant components of cellular functioning
optimal neuro-development
RATIONALE:
  blood plasma levels of omega-3 FAs in children with ASD
 Use of complementary and alternative medicine (CAM) as a Tx for ASD is
common
In WAABR: 54% (92/168) used any type of CAM
48% (81/168) consumed fish oil
Invalidated $
The FAIS Study:
Aim and Study Stages
• To determine if high-dose fish oil
supplementation for 6 months can
improve:
- Behavioural
- Cognitive or
- Language outcomes
in 2-6 year old children with ASD.
More Trials…
• Sleep Intervention – Bright Light Therapy
Rationale:
50-80% of children with ASD have sleep problems
Light is involved in regulating circadian rhythms
Scheduled exposure to bright light may produce a shift in
sleep cycle & reset a person’s sleep pattern, aiding in better
sleep.
 Target 8-11 year olds
PhD student: Amelia Stephens
And, More Trials…
• Acceptance and Commitment Therapy – ACT
 Empirically based psychological intervention
• Aimed to;
parental stress associated with a diagnosis of ASD
parental self-efficacy
parenting coping style
parent-child relationship
PhD student: Tiffany Rochester
Trial Challenges
• Recruitment: Nature of ASD and severity  moral and ethical dilemma
• Access to treatment: medication and App
• Screening for eligibility  strict inclusion / exclusion criteria
• Time and Effort  commitment study requirements  assessments
• Protocol Violations: Compliance ?
• Biological samples: bloods  anxiety
Conclusion
To find out ways to help individuals with autism live the most fulfilling
life possible…
 By conducting methodologically rigorous trials to provide more evidence
The FAB Trial Oxytocin Trial
TOBY Playpad
The FAIS Study
Timely dissemination of evidence  +ve , -ve or null results
to be
published!
 quality evidence base
 shape future research
 informed decision making
 clinical guidance to clinicians
 accurate advice to families
Acknowledgements
FAB Trial
OT Trial
TOBY Trial
The FAIS Study
Prof Dinah Reddihough
Dr Catherine Marraffa
Dr Roshan Virasinghe
Prof Phillip Hazell
A/Prof Michael Kohn
Dr Katherine Lee
Dr John Wray
W/Prof Andrew Whitehouse
Dr Paramala Santosh
Ms Sue Reid
Dr David Dossetor
Dr Natalie Silove
Prof John Carlin
Mr Steven Kloprogge
Ms Anissa Mouti
A/Prof Adam Guastella
Prof Ian Hickie
Ms Lisa Whittle
W/Prof Andrew Whitehouse
Dr John Wray
W/Prof Andrew Whitehouse
Prof Svetha Venkatesh
Mr Darin Cairns
Ms Wendy Marshall
Dr David Trembath
Dr Angelika Anderson
Dr Dennis Moore
Dr Amanda Richdale
Shweta Gupta
Hooi Lit Ng
Matthew Macfarlane
Dr Suzanne Meldrum
W/Prof Karen Simmer
W/Prof Andrew Whitehouse
The University of Sydney
Brain and Mind Research Institute
Royal Children’s Hospital Melbourne
Murdoch Children’s Research Institute
The Children’s Hospital at Westmead
Deakin University
La Trobe University
Monash University
Curtin University
Autism West
The University of Western Australia
For Further Information
[email protected]
[email protected]
 +61 8 9489 7749
http://autism.childhealthresearch.org.au
https://www.facebook.com/#!/TelethonInstituteAutismTeam

Download Report