ANZCTR - Registration

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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

Condition category

Condition code

Neurological

Other neurological disorders

Injuries and Accidents

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]

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]

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]

At baseline and at the end of each week,

Primary outcome [2]

There will be a weekly diary containing questions about side effects,

Timepoint [2]

At baseline and at the end of each week,

Primary outcome [3]

There will be a weekly diary containing questions about medication guesses

Timepoint [3]

At baseline and at the end of each week,

Primary outcome [4]

Medication preferences

Timepoint [4]

At baseline and at the end of each week

Primary outcome [5]

observer comments

Timepoint [5]

At baseline and at the end of each week

Secondary outcome [1]

A shortened 3-question version of the Brief Fatigue Inventory (BFI) will be used to monitor fatigue.

Timepoint [1]

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?

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

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

Funding & Sponsors

Funding source category [1]

Hospital

Name [1]

Royal Childrens' Hospital Foundation

Address [1]

Herston Rd
Herston
Brisbane QLD 4006

Country [1]

Australia

Primary sponsor type

University

Name

The Univesity of Queensland

Address

St Lucia Brisbane Queensland Australia 4072

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

The University of Queensland

Ethics committee address [1]

St Lucia
Brisbane Queensland 4072

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

Approval date [1]

Ethics approval number [1]

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

Address

Country

Phone

Fax

Contact person for public queries

Name

Jane Nikles

Address

School of Medicine
The University of Queensland
Herston Rd
Herston
Brisbane 4006

Country

Australia

Phone

61 7 3374 3898

Fax

uqjnikle@uq.edu.au

Contact person for scientific queries

Name

Jane Nikles

Address

School of Medicine
The University of Queensland
Herston Rd
Herston
Brisbane 4006

Country

Australia

Phone

61 7 3374 3898

Fax

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

Source	Title	Year of Publication	DOI
Dimensions AI	Central 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 trials	2013	https://doi.org/10.1186/1471-2431-13-89

N.B. These documents automatically identified may not have been verified by the study sponsor.

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Documents added manually

Documents added automatically