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Trial registered on ANZCTR


Registration number
ACTRN12608000173392
Ethics application status
Approved
Date submitted
6/04/2008
Date registered
9/04/2008
Date last updated
25/07/2019
Date data sharing statement initially provided
25/07/2019
Date results information initially provided
25/07/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Fluoxetine for the treatment of repetitive behaviours in children and adolescents with autism: A randomised double-blind placebo-controlled trial.
Scientific title
Fluoxetine for the treatment of rigid, repetitive and stereotyped behaviours in children and adolescents with autism: A randomised double-blind placebo-controlled trial.
Secondary ID [1] 283421 0
Nil known
Universal Trial Number (UTN)
Trial acronym
FAB
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Repetitve behaviours in autism. 3006 0
Condition category
Condition code
Mental Health 3156 3156 0 0
Autistic spectrum disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Fluoxetine or placebo (sugar syrup) will be administered as a oral syrup once daily in the morning for 16 weeks. 146 subjects will be randomised into two groups (active and placebo). Total study duration is 22 weeks. Prior to commencement of the trial, a medical history and physical examination will be performed. Four questionnaires will also be administered: Repetitive Behaviour Scale - Revised, Yale-Brown Obsessive Compulsive Scale, Spence Children’s Anxiety Scale, and the Clinical Global Impression Scale. A neuropsychological battery of tests will also be performed. Depending of body weight (< or > 40 kg), the study medication will be commenced at 4 mg or 8 mg/day. Following this, further weekly increments will be made if side effects do not emerge, until an effective dose is reached. The maximum dose utilised will be 20mg or 30 mg/day by week 6. The effective dose will then be maintained between weeks 5 and 16 of the trial. Repeat assessments will be performed in week 16. This testing will include the previously administered questionnaires. Participants will then be weaned off the study medication between weeks 17 and 20.
Intervention code [1] 2746 0
Treatment: Drugs
Comparator / control treatment
Placebo (sugar syrup with raspberry flavouring). The placebo syrup will be of similar appearance and taste to the fluoxetine syrup. The packaging for both will be identical.
Control group
Placebo

Outcomes
Primary outcome [1] 4041 0
Yale-Brown Obsessive Compulsive Scale (CYBOCS)
Timepoint [1] 4041 0
Measured at baseline and at 16 weeks.
Secondary outcome [1] 6802 0
Score for each subscale of the Repetitve Behaviour Scale - Revised (RBS-R).
Timepoint [1] 6802 0
Time point hasn't change (still at 16 weeks), just that initial description was misleading.
Secondary outcome [2] 331137 0
Spence Children's anxiety scale (SCAS) - parent report: total score
Timepoint [2] 331137 0
Measured at baseline and at 16 weeks.
Secondary outcome [3] 331138 0
Aberrant Behaviour Checklist (ABC) - community version total score and subscale scores
Timepoint [3] 331138 0
Measured at baseline and at 16 weeks.
Secondary outcome [4] 331139 0
CGI ‘global improvement’ and ‘efficacy index’ scores
Timepoint [4] 331139 0
Measured at baseline and at 16 weeks.
Secondary outcome [5] 331140 0
Frequency and type of adverse events across the 16 weeks of treatment and 4 weeks of weaning and 2 weeks post completion of the study drug.
Timepoint [5] 331140 0
Adverse events are recorded throughout the 22 weeks duration of the study.

Eligibility
Key inclusion criteria
1. Subjects (both male and female) will be aged between 7.5 years to 18 years.
2. Subjects will need to meet criteria for an Autism Spectrum Disorder [based on the Diagnostic and statistical Manual of Mental Disorder- 4th Edition (DSM-IV) or the International Classification of Diseases (ICD-10) criteria].
3. Subjects must have a score of 6 or greater on the total score of the Children's Yale-Brown Obsessive-Compulsive Scale (CYBOCS) at the time of screening.
4. Subjects must be able to comply with the assessments and procedures required for the trial.
5. Subjects with an intellectual disability must have previously documented psychometric testing.
Minimum age
8 Years
Maximum age
18 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. A DSM-IV diagnosis of Rett’s Disorder, Childhood Disintegrative Disorder, or Schizophrenia.
2. Current use of any psychotropic medication (including typical and atypical anti-psychotics, mood stabilizers, antidepressants, anti-anxiolytics and stimulant medication including atomoxetine, monoamine oxidase inhibitor (MAOI) or pimozide, and St John's wort) or any use of such medication in the 3 months prior to the commencement of the trial.
3. Concomitant administration of drugs that interact with the metabolism of fluoxetine (e.g. phenytoin and carbamazepine).
4. Co-morbid significant medical conditions (e.g. unstable seizure disorder, cardiac disease, liver failure or renal failure).
5. Pregnancy: females of childbearing potential require a urine pregnancy test to exclude pregnancy.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
The Royal Children's Hospital Clinical Epidemiology and Biostatistics Unit will produce an electronic randomisation plan to allow allocation for 68 consecutive study participants. This allocation schedule will be kept by the Clinical Trials Pharmacist at the Royal Chidlren's Hospital Pharmacy Department (who will allocate subjects to the active or placebo group according to this plan). The Clinical Trials Pharmacist will be independent of the trial. The study researchers will not have access to the allocation schedule until the completion of the trial. Therefore all study researchers will remain blinded for the duration of the trial.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation by using a randomization table created by a computer (computerised sequence generation).
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,WA,VIC
Recruitment hospital [1] 1600 0
The Children's Hospital at Westmead - Westmead
Recruitment hospital [2] 1601 0
The Royal Childrens Hospital - Parkville
Recruitment hospital [3] 7398 0
Princess Margaret Hospital - Subiaco
Recruitment postcode(s) [1] 15196 0
6008 - Subiaco

Funding & Sponsors
Funding source category [1] 3265 0
Hospital
Name [1] 3265 0
Department of Developmental Medicine, Royal Chidlren's Hospital
Address [1] 3265 0
Flemington Road, Parkville Vic 3052
Country [1] 3265 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Victorian Medical Insurance Agency
Address
St Kilda Road, Melbourne Vic 3004
Country
Australia
Secondary sponsor category [1] 2919 0
None
Name [1] 2919 0
None
Address [1] 2919 0
None
Country [1] 2919 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 5250 0
Royal Children's Hospital Human Research and Ethics Commitee.
Ethics committee address [1] 5250 0
Flemington Road, Parkville Vic 3052
Ethics committee country [1] 5250 0
Australia
Date submitted for ethics approval [1] 5250 0
22/04/2010
Approval date [1] 5250 0
12/08/2010
Ethics approval number [1] 5250 0
30007
Ethics committee name [2] 5251 0
The Children's hospital at Westmead Human Research Ethics Committee
Ethics committee address [2] 5251 0
The Research Office
Children's Hospital at Westmead
Locked Bad 4001
Westmead NSW 2145
Ethics committee country [2] 5251 0
Australia
Date submitted for ethics approval [2] 5251 0
02/08/2010
Approval date [2] 5251 0
08/05/2011
Ethics approval number [2] 5251 0
10/CHW/88
Ethics committee name [3] 290062 0
CHILD AND ADOLESCENT HEALTH SERVICE (CAHS) RESEARCH ETHICS COMMITTEE
Ethics committee address [3] 290062 0
Ethics Office
Princess Margaret Hospital for Children
GPO Box D184
PERTH WA 6840
Ethics committee country [3] 290062 0
Australia
Date submitted for ethics approval [3] 290062 0
29/08/2010
Approval date [3] 290062 0
05/02/2011
Ethics approval number [3] 290062 0
1847/EP

Summary
Brief summary
Over the last decade, the ‘off label’ use of fluoxetine and other selective serotonin reuptake inhibitor (SSRIs) in children with autism has become increasing common, both in Australia and overseas. However based on the current available literature, the efficacy of SSRIs for the treatment of repetitive behaviours and other symptom domains in autism, is yet to be established. It is therefore of importance that high quality, controlled, and reproducible studies are performed to address the efficacy and safety of SSRIs in children with autism. The aim of this project is to determine the efficacy and safety of Fluoxetine for the treatment of restricted, repetitive and stereotyped behaviours in children and adolescents with autism. Participants will be aged between 7.5 and 18 years, have a known diagnosis of an autism spectrum disorder, and have troublesome restricted, repetitive and stereotyped behaviours causing functional impairment (as defined by the DSM-IV criteria for Autistic Disorder). The study will be a randomised double-blind placebo-controlled trial, with parallel group design. 146 subjects will be randomised into two groups (active and placebo). The duration of participation will be 22 weeks, 16 weeks of study medication. Prior to commencement of the trial, a medical history and physical examination will be performed. Four questionnaires will also be administered: Repetitive Behaviour Scale - Revised, Yale-Brown Obsessive Compulsive Scale, Spence Children’s Anxiety Scale, and the Clinical Global Impression Scale. A neuropsychological battery of tests will also be performed. The study medication will be commenced at 4mg or 8mg/day depending on body weight < or > 40 kg). Following this, further weekly increments will be made if side effects do not emerge, until an effective dose is reached. The maximum dose utilised will be 20mg or 30mg/day by week 4. The effective dose will then be maintained between weeks 5 and 16 of the trial. Repeat assessments will be performed in week 16. This testing will include the previously administered questionnaires. Participants will then be weaned off the study medication between weeks 17 and 20. The active and placebo groups will be compared using independent sample t-tests.
Trial website
http://autism.childhealthresearch.org.au/our-research/fluoxetine-for-autistic-behaviours-(fab)-trial.aspx
Trial related presentations / publications
Mouti A, Reddihough D, Marraffa C, Hazell P, Wray J, Lee K, Santosh P, Reid S, Dossetor D, Silove N, Carlin J, Whitehouse A, Granich J, Kloprogge S, O’Sullivan M, Orsini F, Lockhart P, Clarke S, Poulton A, Kohn M. Multi-Site Randomised Controlled Trial of Fluoxetine in Children and Adolescents with Autism (FAB): Rationale and Design. International meeting for Autism Research (IMFAR), Atlanta, USA, 2014.

Mouti, A., Reddihough, D., Marraffa, C., Hazell, P., Wray, J., Lee, K., & Kohn, M. (2014). Fluoxetine for Autistic Behaviors (FAB trial): study protocol for a randomized controlled trial in children and adolescents with autism. Trials, 15(1), 1.

Public notes

Contacts
Principal investigator
Name 28497 0
Prof Dinah Reddihough
Address 28497 0
Department of Developmental Medicine Royal Children's Hospital Flemington Road, Parkville, Vic 3052
Country 28497 0
Australia
Phone 28497 0
+61 3 9345 5898
Fax 28497 0
Email 28497 0
Dinah.Reddihough@rch.org.au
Contact person for public queries
Name 11654 0
Miss Molly O'Sullivan
Address 11654 0
Developmental Disability & Rehabilitation Research
Murdoch Childrens Research Institute
Level 5 west
Flemington Road Parkville, Victoria 3052, Australia
Country 11654 0
Australia
Phone 11654 0
+61 3 83416229
Fax 11654 0
03 9345 5871
Email 11654 0
molly.osullivan@mcri.edu.au
Contact person for scientific queries
Name 2582 0
Miss Molly O'Sullivan
Address 2582 0
Developmental Disability & Rehabilitation Research
Murdoch Childrens Research Institute
Level 5 west
Flemington Road Parkville, Victoria 3052, Australia
Country 2582 0
Australia
Phone 2582 0
+61 3 83416229
Fax 2582 0
03 9345 5871
Email 2582 0
molly.osullivan@mcri.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary