Trial from ANZCTR


Trial ID ACTRN12609000873224
Trial Status: Registered
Date Submitted: 18/06/2009
Date Registered: 7/10/2009
Retrospectively registered

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Public title N-of-1 trials to evaluate the effect of stimulant vs placebo in pediatric traumatic brain injury
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Study title in 'Participant- Intervention- Comparator- Outcome (PICO)' format 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
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Trial acronym
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Health condition(s) or problem(s) studied:
Traumatic brain injury in children 237066 0
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Condition category: Condition code:
Neurological Other neurological disorders
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237387 237387 0 0
Injuries and Accidents Other injuries and accidents
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Descriptions 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.
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Treatment: drugs 236782 0
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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.
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Control group Placebo
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Primary Outcome: 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. 238187 0
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Timepoint: At baseline and at the end of each week, 238187 0
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Primary Outcome: There will be a weekly diary containing questions about side effects, 253030 0
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Timepoint: At baseline and at the end of each week, 253030 0
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Primary Outcome: There will be a weekly diary containing questions about medication guesses 253031 0
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Timepoint: At baseline and at the end of each week, 253031 0
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Primary Outcome: Medication preferences 253032 0
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Timepoint: At baseline and at the end of each week 253032 0
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Primary Outcome: observer comments 253033 0
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Timepoint: At baseline and at the end of each week 253033 0
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Secondary Outcome: A shortened 3-question version of the Brief Fatigue Inventory (BFI) will be used to monitor fatigue. 242493 0
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Timepoint: The BFI will be measured via self-report at baseline and at the end of each week, along with the weekly diaries mentioned above. 242493 0
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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.
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Minimum age 6 Years
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Maximum age 16 Years
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Gender Both males and females
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Healthy volunteers? No
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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.
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Study type Interventional
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Purpose of the study Treatment
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Allocation to intervention Randomised controlled trial
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Describe the procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Describe the methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
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Who is / are masked / blinded (choose all that apply)


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Assignment
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Phase
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Anticipated date of first participant enrolment 1/01/2009
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Date of first participant enrolment
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Anticipated date last participant recruited/enrolled
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Actual date last participant recruited/enrolled
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Target sample size 42
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Recruitment status Recruiting
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Recruitment in Australia

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Recruitment outside Australia

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Funding Source: Hospital 237181 0
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Name: Royal Childrens' Hospital Foundation 237181 0
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Address: Herston Rd
Herston
Brisbane QLD 4006
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Country: Australia 237181 0
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Primary Sponsor University
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Name: The Univesity of Queensland
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Address: St Lucia Brisbane Queensland Australia 4072
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Country: Australia
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Secondary Sponsor: None 4674 0
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Has the study received approval from at least one Ethics Committee? Yes
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Ethics Committee name: The University of Queensland 239274 0
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Address: St Lucia
Brisbane Queensland 4072
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Country: Australia 239274 0
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Approval Date: 239274 0
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HREC: 239274 0
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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.
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Trial website
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Principal Investigator
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Contact person for public queries
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Name: Jane Nikles
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Address: School of Medicine The University of Queensland Herston Rd Herston Brisbane 4006
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Tel: 61 7 3374 3898
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Email: uqjnikle@uq.edu.au
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Contact person for scientific queries
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Name: Jane Nikles
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Address: School of Medicine The University of Queensland Herston Rd Herston Brisbane 4006
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Contact person responsible for updating information
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Name: Jane Nikles
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Address: School of Medicine The University of Queensland Herston Rd Herston Brisbane 4006
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Addition Cancer fields
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