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Trial registered on ANZCTR


Registration number
ACTRN12609000865213
Ethics application status
Approved
Date submitted
1/10/2008
Date registered
6/10/2009
Date last updated
6/10/2009
Type of registration
Retrospectively registered

Titles & IDs
Public title
N-of-1 Trials of Stimulant (dexamphetamine or methylphenidate) vs Placebo for Paediatric Traumatic Brain Injury
Scientific title
N-of-1 Trials of Stimulant (dexamphetamine or methylphenidate) vs Placebo on Attention and Concentration Disorders and Executive Dysfunction for Paediatric Traumatic Brain Injury
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Traumatic Brain Injury 3770 0
Condition category
Condition code
Physical Medicine / Rehabilitation 3945 3945 0 0
Other physical medicine / rehabilitation

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Methylphenidate or dexamphetamine.

Prior to the trial, if not already stabilised on either methylphenidate or dexamphetamine, the child will be stabilised on an appropriate dose of methylphenidate or dexamphetamine. The duration of stabilisation will be determined individually by each patient’s doctor. The dosage and frequency of tablets during the stabilisation period will also be determined individually by each patient’s doctor.

Trial medication dose will be individualised to determine the dose that delivers apparent improvements in behaviour with [positive effects on school and home performance and which tolerated with minimal side effects. This will become the trial dose for that patient. The dosage and frequency of tablets during the trial period will also be determined individually by each patient’s doctor.

Either stimulant will be taken orally as per approved dosage recommendations. Medication dose will be individualised as encapsulation will be used to make the active and placebo medication identical. The trial drugs will be purchased at wholesale prices, and an accredited compound pharmacist will organise encapsulation, randomisation, and packaging of the medication in Webster packs. The pharmacy will produce 3 X 1 week’s supply of active medication and 3 X 1 week’s supply of placebo, in capsule form. Active stimulants and placebo will be presented as identical opaque capsules, with encapsulation of the active whole tablet, and of placebo.

Each treatment period will last for one week. Each participant will complete 3 weeks of active medication and 3 weeks of placebo, in a randomised order, so that there will be a total of six consecutive treatment periods. The active medication (methylphenidate or dexamphetamine) has a very short half-life, however to allow for washout of the medication, data from the first two days of each treatment period will not be used, so that only the last 5 days of each week will be used.
Intervention code [1] 3482 0
Treatment: Drugs
Comparator / control treatment
Placebo (Avicil).

Presented as identical opaque capsules to active drug. Made specifically for this trial by an accredited compound pharmacist.
Control group
Placebo

Outcomes
Primary outcome [1] 4850 0
To determine whether Stimulant therapy with methylphenidate (MPH) or dexamphetamine compared to placebo will significantly improve attention and concentration, and executive dysfunction including disorders of behavioural and emotional regulation, in children with Traumatic Brain Injury (TBI).

This will be measured using the Conners Teacher and Parent self-reported revised short form ratings scales, and The Goal Attainment Scale.
Timepoint [1] 4850 0
At the end of each treatment period. Each treatment period will last for one week. There will be a total of six consecutive treatment periods.
Secondary outcome [1] 8194 0
Fatigue. As measured by the Brief Fatigue Inventory.
Timepoint [1] 8194 0
At the end of each treatment period.
Each treatment period will last for one week. There will be a total of six consecutive treatment periods.
Secondary outcome [2] 8195 0
Side effects of the drugs. As measured by the modified Barkley Side Effects Questionnaire
Timepoint [2] 8195 0
At the end of each treatment period. Each treatment period will last for one week. There will be a total of six consecutive treatment periods.

Eligibility
Key inclusion criteria
1) Any school age (6-16 years) patient with a clinical diagnosis of moderate to severe brain injury who is at least 12 months post injury. Severity criteria are based on Glasgow coma scale (GCS) criteria ie for moderate TBI = GCS of 9-13 at presentation to the treating hospital and severe TBI = initial GCS 3-8/15. 2) The child has a clinically significant attention/concentration disorder or executive dysfunction including disorders of
behavioural or emotional regulation that may respond to stimulants. 3) Patient, parent and doctor would like to use the n-of-1 trial methodology to see if the patient is a true responder to the stimulant. 4) Patients and parents are willing to consent and participate, and to continue treatment with the medication if it is shown to be effective in their case. 5) The patient is in a community setting. 6) At least two people (parent and teacher or other person) are available to monitor the child’s symptoms.
Minimum age
6 Years
Maximum age
16 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Uncontrolled seizure disorder, moderate to severe hypertension, clinically significant anxiety, motor tics, Tourette syndrome, suspected or proven cardiac conduction problems, idiosyncratic reaction to sympathomimetic amines, history of drug abuse (including high caffeine beverages and appetite suppressants). Parents not able to fill out forms in English.

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)
Queensland Paediatric Rehabilitation Service (QPRS) is the principal paediatric service in Queensland managing patients 12 months or more post TBI. It has outreach clinics in various locations across the state. It has 500 or so brain injury patients on its database and has received 36 new referrals (not necessarily with recent injuries) so far this year. The NSW sites, both with previous experience in stimulant trials, have a total of 2000 patients on their brain injury database. If 20-46% of patients have clinically significant disorders of attention 1-4 years post-injury, at least 500 patients should be eligible to be screened.

Initial contact will be made with participants through their doctor, who will mention the study to them during a consultation and give them an information sheet to take
home and read. If the doctor and patient decide to participate in this trial, then the doctor will refer the patient to the trial research team, who hold the allocation sequence.

Children already on long-acting methylphenidate (MPH) and those who are judged likely to benefit from this will be offered long-acting MPH trials at their clinician’s discretion. Other children will be offered trials of short-acting MPH, or dexamphetamine.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Random allocation of the order of the medicines within the six treatrment periods is determined by computer.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
n-of-1 trials will provide a direct head to head comparison between stimulant and placebo, allowing aim 1 to be achieved in each individual patient.

To achieve aim 2, individual semi-structured interviews will be conducted with key informants to identify process issues around the conduct of n-of-1 trials. Such issues include the applicability of the n-of-1 trial method in pediatric rehabilitation services, timeliness of delivery of patient results to the treating clinician, appropriateness of the format in which the results are presented to the clinician, usefulness of patient results, utility in clinical decision making, and patient/carer/teacher perspectives on trial usefulness and effort required for keeping the diary etc.
Phase
Phase 3
Type of endpoint(s)
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
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)
Recruitment postcode(s) [1] 1186 0
4029
Recruitment postcode(s) [2] 1187 0
2031
Recruitment postcode(s) [3] 1188 0
2145

Funding & Sponsors
Funding source category [1] 3946 0
Hospital
Name [1] 3946 0
Royal Children's Hospital Foundation
Address [1] 3946 0
Royal Children's Hospital Foundation
PO Box 99
Royal Brisbane Hospital
QLD 4029
Country [1] 3946 0
Australia
Funding source category [2] 3947 0
University
Name [2] 3947 0
The University of Queensland
Address [2] 3947 0
The University of Queensland
Sir Fred Schonell Dr
Brisbane
QLD 4072
Country [2] 3947 0
Australia
Primary sponsor type
Government body
Name
Motor Accident Insurance Commission
Address
Level 9, 33 Charlotte Street
GPO Box 1083
BRISBANE
QLD 4001
Country
Australia
Secondary sponsor category [1] 3546 0
None
Name [1] 3546 0
Address [1] 3546 0
Country [1] 3546 0
Other collaborator category [1] 439 0
Hospital
Name [1] 439 0
Royal Children's Hospital
Address [1] 439 0
Royal Children's Hospital
Herston Road
HERSTON
QLD 4029
Country [1] 439 0
Australia
Other collaborator category [2] 440 0
Hospital
Name [2] 440 0
Sydney Children's Hospital
Address [2] 440 0
Sydney Children's Hospital
High Street
Randwick
NSW 2031
Country [2] 440 0
Australia
Other collaborator category [3] 441 0
Hospital
Name [3] 441 0
The Children's Hopsital at Westmead
Address [3] 441 0
The Children's Hospital at Westmead
Locked Bag 4001
Westmead
NSW 2145
Country [3] 441 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 6018 0
The University of Queensland Medical Research
Ethics committee address [1] 6018 0
The University of Queensland
Sir Fred Schonell Dr
Brisbane
QLD 4072
Ethics committee country [1] 6018 0
Australia
Date submitted for ethics approval [1] 6018 0
Approval date [1] 6018 0
30/04/2008
Ethics approval number [1] 6018 0
2008000808
Ethics committee name [2] 6019 0
Royal Children's Hospital Human Research Ethics
Ethics committee address [2] 6019 0
Lvl 3, RCH Foundation Building
Royal Children's Hospital
Herston
QLD 4029
Ethics committee country [2] 6019 0
Australia
Date submitted for ethics approval [2] 6019 0
Approval date [2] 6019 0
18/03/2008
Ethics approval number [2] 6019 0
2008/024
Ethics committee name [3] 6020 0
Catholic Education, Archdiocese of Brisbane
Ethics committee address [3] 6020 0
GPO Box 1201
Brisbane
QLD 4001
Ethics committee country [3] 6020 0
Australia
Date submitted for ethics approval [3] 6020 0
Approval date [3] 6020 0
19/08/2008
Ethics approval number [3] 6020 0
481
Ethics committee name [4] 6021 0
Strategic Policy and Performance. Department of Education, Training, and the Arts
Ethics committee address [4] 6021 0
PO Box 15033
City East Brisbane
QLD 4002
Ethics committee country [4] 6021 0
Australia
Date submitted for ethics approval [4] 6021 0
11/08/2008
Approval date [4] 6021 0
Ethics approval number [4] 6021 0
Ethics committee name [5] 6022 0
Royal Alexandra Hospital for Children Ethics
Ethics committee address [5] 6022 0
Research Office
Clinical Sciences Building
The Children's Hospital at Westmead
Locked Bag 4001
WESTMEAD
NSW 2125
Ethics committee country [5] 6022 0
Australia
Date submitted for ethics approval [5] 6022 0
01/11/2008
Approval date [5] 6022 0
Ethics approval number [5] 6022 0
Ethics committee name [6] 6023 0
South Eastern Sydney and Illawarra Area Health - Northern Network
Ethics committee address [6] 6023 0
South Eastern Sydney Area Health Service - Eastern Section
Administration Centre, Edmund Blackett Building
Cnr Avoca and High Streets
RANDWICK
NSW 2031
Ethics committee country [6] 6023 0
Australia
Date submitted for ethics approval [6] 6023 0
01/11/2008
Approval date [6] 6023 0
Ethics approval number [6] 6023 0

Summary
Brief summary
This proposal will provide solutions to a very significant practical clinical question in paediatric brain injury rehabilitation: Can stimulant medication improve disorders of attention and concentration, and other
problems including regulation of behaviour and emotions, in children with traumatic brain injury (TBI), and thus facilitate rehabilitation? Few studies have investigated the usefulness of stimulant medication in children with TBI. It is well recognised that there is marked individual variation in response to stimulant medication. Positive effects from stimulants in this population (such as improved attention and concentration and better emotional and behavioural regulation) will allow children to benefit more from rehabilitation interventions and result in more cost-effective rehabilitation.

N-of-1 trials (a type of drug trial in which the effect of the drug is examined within each individual patient rather than between groups of patients) will be used to examine the efficacy of stimulants in individual
patients with Traumatic Brain Injury, so that the doctor, patient and family can make an objective assessment about the usefulness of this treatment for the patient.

We will conduct n-of-1 trials of stimulants compared to placebo to test their efficacy for these symptoms in 42 children from 2 Australian states, preceded by an initial pilot in 10 children from Queensland. For
responders, using treatment supported by the best possible evidence will facilitate patients recovery from TBI, make rehabilitation more cost-effective and greatly improve academic and life prospects and QOL for patients and families.

AIMS The hypotheses we plan to test are: (1) Stimulant therapy with methylphenidate (MPH) or dexamphetamine compared to placebo will significantly improve attention and concentration, and executive
dysfunction including disorders of behavioural and emotional regulation, in children with TBI. (2) n-of-1 trials
are feasible in paediatric rehabilitation practice for children with TBI.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 28988 0
Address 28988 0
Country 28988 0
Phone 28988 0
Fax 28988 0
Email 28988 0
Contact person for public queries
Name 12145 0
Sue-Ann Carmont
Address 12145 0
Centre for General Practice
School of Medicine
The University of Queensland
Lvl2, Edith Cavell
Royal Brisbane Hospital
Herston
QLD 4029
Country 12145 0
Australia
Phone 12145 0
+61 7 33655014
Fax 12145 0
+61 7 33655130
Email 12145 0
s.carmont@uq.edu.au
Contact person for scientific queries
Name 3073 0
Sue-Ann Carmont
Address 3073 0
Centre for General Practice
School of Medicine
The University of Queensland
Lvl2, Edith Cavell
Royal Brisbane Hospital
Herston
QLD 4029
Country 3073 0
Australia
Phone 3073 0
+61 7 33655014
Fax 3073 0
+61 7 33655130
Email 3073 0
s.carmont@uq.edu.au

No information has been provided regarding IPD availability
Summary results
No Results