N-of-1 Trials of Stimulant (dexamphetamine or methylphenidate) vs Placebo for Paediatric Traumatic Brain Injury
N-of-1 Trials of Stimulant (dexamphetamine or methylphenidate) vs Placebo on Attention and Concentration Disorders and Executive Dysfunction for Paediatric Traumatic Brain Injury
Motor Accident Insurance Commission
52 participants
Oct 13, 2008
Interventional
Conditions
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.
Eligibility
Inclusion Criteria2
- 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.
Exclusion Criteria1
- 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.
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Interventions
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.
Locations(1)
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ACTRN12609000865213