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Trial registered on ANZCTR


Registration number
ACTRN12609000873224
Ethics application status
Approved
Date submitted
18/06/2009
Date registered
7/10/2009
Date last updated
7/10/2009
Type of registration
Retrospectively registered

Titles & IDs
Public title
N-of-1 trials to evaluate the effect of stimulant vs placebo in pediatric traumatic brain injury
Scientific title
N-of-1 trials of stimulant vs placebo for pediatric traumatic brain injury on Attention-deficit/hyperactivity disorder (ADHD) index scores as well as scores for cognitive problems/attention, hyperactivity and oppositional scores in pediatric traumatic brain injury
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Traumatic brain injury in children 237066 0
Condition category
Condition code
Neurological 237387 237387 0 0
Other neurological disorders
Injuries and Accidents 252163 252163 0 0
Other injuries and accidents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
n-of-1 trials will be offered to patients of the Brain Injury Service at the children's hospital at Westmead and Queensland Paediatric Rehabilitation Service (QPRS) (which provides services for patients from all over Queensland). Sydney Children’s Hospital will also be involved. Rehabilitation staff in all relevant clinics will be informed about the availability of the trials. Doctors will be responsible for potential patients, and for the post-trial consultation. Clinic nurses will explain the process and obtain informed consent. Parents will provide informed consent, and children over 12 assent. The trial will be set up and co-ordinated from Queensland via registered post of medication packages and regular telephone support of patients/families. Queensland will report the trial results to individual clinicians throughout the study. As well as being involved in trial and questionnaire design and reporting and disseminating the results, the Sydney hospitals' role will be to identify possible subjects, gain informed consent and continue their clinical care. During the n-of-1 trial, the patient will undergo three cycles of 2 x 1 week treatment periods – a total of 6 weeks. Each active drug (dexamphetamine or methlylphenidate) will be compared against placebo, in random order. An example treatment order might be:
PA AP PA (where P is placebo and A is active).
There will be no break in between treatments. Doses will be individualised by the patients' doctors so that the patient is on the optimal dose of stimulant (by oral apsule). Some will be taking once a day medication and some will on morning and noon doses.
The first 2 days of each treatment period will not be used to allow for washout of active medications (half-lives: methylphenidate (MPH) 4 hours; dexamphetamine 6-8 hours). Questionnaires will ask about “the last 5 days”. The actual day of starting will be randomized to avoid confounding by fatigue effects as the week goes on. Trials can span school holidays because remaining cycles can be completed after a break. Concomitant therapy may be used as required for other conditions.
Intervention code [1] 236782 0
Treatment: Drugs
Comparator / control treatment
placebo will be identical to the active (eg as doese are individualised, if a patient takes a 5 mg capsule placebo will be an identical 5 mg capsule). The placebo will be an inert substance such as cornstarch.
Control group
Placebo

Outcomes
Primary outcome [1] 238187 0
a) Conners Teacher and Parent self-reported revised short form rating scales (8, 9). A self report scale for those over 12 years whose clinicians decide they are able to fill out the forms will also be available (Conners-Wells adolescent rating scales). These will measure overall ADHD index scores as well as scores for cognitive problems/attention, hyperactivity and oppositional scores.
Timepoint [1] 238187 0
At baseline and at the end of each week,
Primary outcome [2] 253030 0
There will be a weekly diary containing questions about side effects,
Timepoint [2] 253030 0
At baseline and at the end of each week,
Primary outcome [3] 253031 0
There will be a weekly diary containing questions about medication guesses
Timepoint [3] 253031 0
At baseline and at the end of each week,
Primary outcome [4] 253032 0
Medication preferences
Timepoint [4] 253032 0
At baseline and at the end of each week
Primary outcome [5] 253033 0
observer comments
Timepoint [5] 253033 0
At baseline and at the end of each week
Secondary outcome [1] 242493 0
A shortened 3-question version of the Brief Fatigue Inventory (BFI) will be used to monitor fatigue.
Timepoint [1] 242493 0
The BFI will be measured via self-report at baseline and at the end of each week, along with the weekly diaries mentioned above.

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 traumatic brain injury (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
Sex
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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/01/2009
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
42
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 237181 0
Hospital
Name [1] 237181 0
Royal Childrens' Hospital Foundation
Country [1] 237181 0
Australia
Primary sponsor type
University
Name
The Univesity of Queensland
Address
St Lucia Brisbane Queensland Australia 4072
Country
Australia
Secondary sponsor category [1] 4674 0
None
Name [1] 4674 0
Address [1] 4674 0
Country [1] 4674 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 239274 0
The University of Queensland
Ethics committee address [1] 239274 0
St Lucia
Brisbane Queensland 4072
Ethics committee country [1] 239274 0
Australia
Date submitted for ethics approval [1] 239274 0
Approval date [1] 239274 0
Ethics approval number [1] 239274 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, make rehabilitation professionals’ jobs easier 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.

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. Objectives: A) To determine the efficacy of stimulants in alleviating these symptoms in children with traumatic brain injury. B) To evaluate the feasibility of n-of-1 trials as a means of conducting clinical trials in paediatric rehabilitation.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 29773 0
Address 29773 0
Country 29773 0
Phone 29773 0
Fax 29773 0
Email 29773 0
Contact person for public queries
Name 13020 0
Jane Nikles
Address 13020 0
School of Medicine
The University of Queensland
Herston Rd
Herston
Brisbane 4006
Country 13020 0
Australia
Phone 13020 0
61 7 3374 3898
Fax 13020 0
Email 13020 0
uqjnikle@uq.edu.au
Contact person for scientific queries
Name 3948 0
Jane Nikles
Address 3948 0
School of Medicine
The University of Queensland
Herston Rd
Herston
Brisbane 4006
Country 3948 0
Australia
Phone 3948 0
61 7 3374 3898
Fax 3948 0
Email 3948 0
uqjnikle@uq.edu.au

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
Dimensions AICentral nervous system stimulants for secondary attention deficit-hyperactivity disorder after paediatric traumatic brain injury: a rationale and protocol for single patient (n-of-1) multiple cross-over trials2013https://doi.org/10.1186/1471-2431-13-89
N.B. These documents automatically identified may not have been verified by the study sponsor.