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Trial registered on ANZCTR


Registration number
ACTRN12612000484842
Ethics application status
Approved
Date submitted
1/05/2012
Date registered
2/05/2012
Date last updated
31/05/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
Efficacy of methylphenidate and Attention Process Training in traumatic brain injury rehabilitation
Scientific title
The effect of methylphenidate and Attention Process Training versus placebo on neuropsychological measures of speed of information processing, complex attentional functioning, and everyday attentional behaviour following moderate to severe traumatic brain injury
Secondary ID [1] 280426 0
Nil
Universal Trial Number (UTN)
U1111-1130-2644
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Traumatic Brain Injury (TBI) 286393 0
Condition category
Condition code
Injuries and Accidents 286644 286644 0 0
Other injuries and accidents
Physical Medicine / Rehabilitation 286645 286645 0 0
Other physical medicine / rehabilitation
Neurological 286652 286652 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Arm 1 – TBI- Methylphenidate and Attention Process Training
Arm 2 – TBI- Methylphenidate
Arm 3 – TBI- Attention Process Training and Placebo
Arm 4 – TBI- Placebo
Arm 5 – Healthy control participants

Methylphenidate will be Ritalin LA capsules equivalent to a dose of Ritalin IR (immediate release) 0.3 mg/kg twice daily (bid). A maximum daily upper limit will be set at 60 mg bid. Lactose in identical capsules will serve as placebo. Methylphenidate and placebo will be administered daily at 8am for 7 weeks.

A qualified clinical neuropsychologist will deliver the computer-based Attention Process Training (including strategy training). Attention Process Training is an attention training program that consists of a series of computer-based visual and auditory exercises designed to rehabilitate attention deficits. Attention Process Training exercises include tasks such as matching clock times, listening for two numbers amongst a sequence, watching for multiples of 3, and matching faces and emotions. The tasks start off quite easy and get progressively more challenging as the participant demonstrates that they have mastered that skill. Attention Process Training sessions will last for 45 minutes and will occur three times a week for 6 weeks.

In week 1 all participants (arms 1-5) will complete a baseline assessment. The healthy control participants (arm 5) will only complete the baseline assessment with results used to further delineate the types and severity of attention deficits following traumatic brain injury.

The traumatic brain injury patients (arms 1-4) will then take the drug (methylphenidate or placebo) for 7 weeks. Participants in arms 1 and 3 will receive Attention Process Training for 6 weeks. Two assessments will occur in week 8 (on the drug) and week 9 (drug-free). A follow-up assessment will occur at 6-months.
Intervention code [1] 284784 0
Treatment: Drugs
Intervention code [2] 284785 0
Treatment: Other
Intervention code [3] 284786 0
Rehabilitation
Comparator / control treatment
Placebo (0.3 mg/kg bid of lactose) will be administered at 8am daily for 7 weeks in a capsule identical to those used to administer the methylphenidate.
Control group
Placebo

Outcomes
Primary outcome [1] 287048 0
Performance on standard cognitive measures (Paced Auditory Serial Addition Test, Symbol Digit Modalities Test, Ruff 2&7 Selective Attention Test, N-back, Computerised Selective Attention Task).
Timepoint [1] 287048 0
Week 1, week 8 (on drug), week 9 (drug free), and 6-month follow-up.
Primary outcome [2] 287049 0
Performance on The Rating Scale of Attentional Behaviour as rated by a treating therapist and significant other.
Timepoint [2] 287049 0
Week 1, week 8 (on drug), week 9 (drug free), and 6-month follow-up.
Primary outcome [3] 287050 0
Functional outcome performance as measured with responses of the TBI patient, a significant other, and a treating therapist on The Mayo-Portland Adaptability Inventory.
Timepoint [3] 287050 0
Week 1 and 6-month follow-up.
Secondary outcome [1] 297270 0
Side effects as measured on a modified version of the Moss Rehabilitation Research Institute Side Effects Monitoring Form, and blood pressure and heart rate measurements.

Previous studies suggest that side effects are not likely to occur frequently or severely. It is unlikely that participants will experience significant discomfort or harm from participating in this study, however possible side effects may include decreased appetite, nervousness, insomnia, irritability, headache, drowsiness, dizziness, increased heart rate and/or blood pressure, dry mouth, nausea or rash. Participants may have none, some or all of these effects.
Timepoint [1] 297270 0
Weekly for 7 weeks.

Eligibility
Key inclusion criteria
Traumatic brain injury:
Moderate to severe traumatic brain injury within the preceding 12 months and demonstrated attentional impairment.

Healthy controls:
Recruited from the general population.
Minimum age
16 Years
Maximum age
60 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Traumatic Brain Injury:
Inadequate English, physical abilities or cognitive abilities to complete the tasks or training, past history of treatment for drug or alcohol dependence, previous neurological history, treatment with medications for which methylphenidate is contraindicated, or current medical conditions for which methylphenidate is contraindicated.

Healthy controls:
Inadequate English, physical abilities or cognitive abilities to complete the tasks, a history of neurological or psychiatric trauma or illness, a history of treatment for attentional difficulties or disorders including Attention Deficit Hyperactivity Disorder.

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)
An independent researcher will create a blocked randomisation table, which they will forward on to an independent pharmacy. Recruitment to the trial will be completed initially by the patient’s rehabilitation physician and followed-up by the researchers involved in the study. Once recruited, the participant will be allocated a study ID number. A prescription containing the participant’s study ID number will be sent to the independent pharmacy, which will dispense the appropriate drug (methylphenidate or placebo) based on the randomisation table.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
An independent researcher will create a permuted block randomisation table. Blocks will be of varying sizes and the order of the blocks will be randomly determined using a simple randomisation table created by computer software. The researchers recruiting the participants will be blinded to the order of the block presentation.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Participants will be blinded to the placebo/methylphenidate treatment, but obviously will not be blinded to the Attention Process Training intervention.
Phase
Phase 4
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Date of first participant enrolment
Anticipated
21/05/2012
Actual
28/08/2012
Date of last participant enrolment
Anticipated
Actual
3/09/2013
Date of last data collection
Anticipated
Actual
Sample size
Target
160
Accrual to date
Final
61
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 5875 0
Epworth Richmond - Richmond
Recruitment hospital [2] 5876 0
Epworth Rehabilitation Camberwell - Camberwell
Recruitment postcode(s) [1] 5258 0
3121
Recruitment postcode(s) [2] 13317 0
3124 - Camberwell

Funding & Sponsors
Funding source category [1] 285181 0
University
Name [1] 285181 0
Monash University
Country [1] 285181 0
Australia
Funding source category [2] 293723 0
Charities/Societies/Foundations
Name [2] 293723 0
Epworth Research Institute
Country [2] 293723 0
Australia
Primary sponsor type
University
Name
Monash University
Address
School of Psychology and Psychiatry, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton Campus, Wellington Road, Clayton, Victoria 3800, Australia
Country
Australia
Secondary sponsor category [1] 284049 0
None
Name [1] 284049 0
Address [1] 284049 0
Country [1] 284049 0
Other collaborator category [1] 260778 0
Hospital
Name [1] 260778 0
Epworth HealthCare
Address [1] 260778 0
89 Bridge Road, Richmond, Victoria 3121, Australia
Country [1] 260778 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 287189 0
Epworth Human Research Ethics Committee
Ethics committee address [1] 287189 0
HREC Coordinator, Human Research Ethics Committee, Epworth HealthCare, Pelaco Building One, 21-31 Goodwood Street, Richmond, Victoria, 3121
Ethics committee country [1] 287189 0
Australia
Date submitted for ethics approval [1] 287189 0
Approval date [1] 287189 0
26/10/2011
Ethics approval number [1] 287189 0
53311
Ethics committee name [2] 287190 0
Monash University Human Research Ethics Committee
Ethics committee address [2] 287190 0
Human Ethics Office, First Floor, Building 3e, Monash Research Office, Clayton Campus, Monash University, Victoria 3800, Australia
Ethics committee country [2] 287190 0
Australia
Date submitted for ethics approval [2] 287190 0
Approval date [2] 287190 0
16/03/2012
Ethics approval number [2] 287190 0
CF11/3401 - 2011001815

Summary
Brief summary
The aim of this study is to investigate the efficacy of methylphenidate combined with individualised Attention Process Training (APT-3) in enhancing performance on neuropsychological measures of speed of thinking, complex attentional functions, and everyday attentional behaviour in a seven week randomised, placebo-controlled drug trial, with functional follow-up at 6 months. A secondary aim is to identify which factors, including injury severity and baseline attentional performance, will be associated with response to Attention Process Training and methylphenidate interventions.
Trial website
Trial related presentations / publications
Publications:
Dymowski, A. R., Ponsford, J. L., Owens, J. A., Olver, J. H., Ponsford, M. & Willmott, C. (In Press). The efficacy and safety of extended-release methylphenidate following traumatic brain injury: A randomised controlled pilot study. Clinical Rehabilitation.

Dymowski, A. R., Owens, J. A., Ponsford, J. L. & Willmott, C. (2015). Speed of processing and strategic control of attention after traumatic brain injury. Journal of Clinical and Experimental Neuropsychology, 37(10), 1024-1035. doi: 10.1080/13803395.2015.1074663.

Presentations:
Dymowski. A., Ponsford, J. L., Willmott, C., Owens, J., Richardson, C. J. & Spitz, G. Attention and executive functioning following traumatic brain injury. Poster presentation at Epworth Research Week, Epworth HealthCare, Melbourne, Australia, 15 June 2015.

Dymowski. A., Ponsford, J. L., Willmott, C., Owens, J., Richardson, C. J. & Spitz, G. Attention and executive functioning following traumatic brain injury. Poster presentation at the Psychology Clinical Translation Showcase, Monash University, Melbourne, Australia, 1 December 2014.

Dymowski. A., Ponsford, J. L., Willmott, C., Owens, J., Richardson, C. J. & Spitz, G. Attention and executive functioning following traumatic brain injury. Poster presentation at the 20th APS CCN Conference, Adelaide, Australia, 27-29 November 2014.

Dymowski. A., Ponsford, J. L., Willmott, C., Owens, J., Richardson, C. J. & Spitz, G. Attention and executive functioning following traumatic brain injury. Poster presentation at the Mid-Year Meeting of the International Neuropsychological Society, Jerusalem, Israel, 9-11 July 2014.
Public notes

Contacts
Principal investigator
Name 34127 0
Prof Jennie Ponsford
Address 34127 0
Monash-Epworth Rehabilitation Research Centre, 185-187 Hoddle Street, Richmond, 3121, Victoria
Country 34127 0
Australia
Phone 34127 0
+61 3 9426 8923
Fax 34127 0
Email 34127 0
[email protected]
Contact person for public queries
Name 17374 0
Alicia Dymowski
Address 17374 0
Monash-Epworth Rehabilitation Research Centre, 185 Hoddle Street, Richmond, Victoria 3121, Australia
Country 17374 0
Australia
Phone 17374 0
+61 3 94268923
Fax 17374 0
Email 17374 0
[email protected]
Contact person for scientific queries
Name 8302 0
Prof. Jennie Ponsford
Address 8302 0
Monash-Epworth Rehabilitation Research Centre, 185 Hoddle Street, Richmond, Victoria 3121, Australia
Country 8302 0
Australia
Phone 8302 0
+61 3 94268923
Fax 8302 0
Email 8302 0
[email protected]

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