None listed
Conditions
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.
Interventions
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
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.
Sponsors
The Univesity of Queensland
Study design
Allocation
Randomised controlled trial
Primary purpose
Treatment
Eligibility
Sex/Gender
All
Age
6 Years to 16 Years
Healthy volunteers
No
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.
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.
Outcome results
None listed