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Trial registered on ANZCTR


Registration number
ACTRN12620000499987
Ethics application status
Approved
Date submitted
26/03/2020
Date registered
21/04/2020
Date last updated
22/04/2020
Date data sharing statement initially provided
21/04/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
The effect of an acute Methylphenidate (Ritalin®) dose on cognition, behaviour and driving performance in healthy volunteers
Scientific title
Effect of acute Methylphenidate (Ritalin®) dose on visual attention, subjective mood assessments and driving performance in healthy volunteers
Secondary ID [1] 300706 0
None
Universal Trial Number (UTN)
Trial acronym
RAD
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Attention deficits 316520 0
Condition category
Condition code
Mental Health 314765 314765 0 0
Studies of normal psychology, cognitive function and behaviour

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Over the two-week experimental period, participants will receive all of the experimental doses.

One dose will be taken at each session [i.e. active Methylphenidate (Ritalin) or placebo Methylphenidate (Ritalin)] and the order of dosing will be randomised.

The active treatment is:
1. Methylphenidate (Ritalin) 10mg

The placebo treatments are:

1. Placebo tablet (identical in taste, texture, weight and smell). Microcellulose tablet

A one-week washout period will occur between testing sessions.

Prior to dosing at each testing visit (each at V1 and V2), participants will provide one saliva sample to screen for evidence of recent use of drugs [amphetamine/d-methamphetamine, 3,4- methylenedioxymethamphetamine (MDMA), cocaine, cannabis (del ta-9-tetrahydrocannabinol) and opiates] using the Securetec DrugWipe 6s device. This screening assessment requires an absorbent pad to be placed over the tongue for approximately 20 seconds. 1ml of saliva will be taken per sample, therefore approximately 4ml in total over each of the four experimental sessions. A sample volume of less than 10 micro litres is sufficient for analysis. The device is wiped on the tongue, when the colour has changed from pink to yellow there is the required amount of saliva to obtain the results.

A registered research nurse trained in venepuncture or a qualified venepuncture technician will collect one blood samples at each testing session (each at V1, V2): after the final cognitive assessment.

The CogTrack™ System will be used to assess the cognitive effects of the intervention. Three tasks will be used in this study to assess visual processing, processing speed and reaction/decision speed, specifically: Digit vigilance, Spatial working memory, Numeric working memory, Simple Reaction Time and Choice Reaction Time. Participants will be assessed at approximately 30 minutes post-dosing and at 2.5 hours post dosing.

Driving performance will be assessed using the Forum 8 driving simulator, and driving performance will be assessed once per study session, for a 40 minute duration. The simulator consists of a car unit with adjustable car seats and a dashboard and includes a steering wheel, turn sign indicators, gear lever, brake and accelerator pedals for vehicle control. The system generates realistic roadway scenery which is presented on three integrated TV screens 1.90 meters in front of the centre of the steering wheel. The speed and gear number are displayed on the dashboard and screen. Auditory feedback is provided by speakers and included the sound of the engine, braking, speeding in curves, and driving off-road. Driving assessment will take place at approximately 1.5 hours post dosing.
Intervention code [1] 317030 0
Treatment: Drugs
Comparator / control treatment
Placebo tablet (identical in taste, texture, weight and smell). Microcellulose tablet
Control group
Placebo

Outcomes
Primary outcome [1] 323115 0
Associations between Methylpheniate (Ritalin) and cognitive performance (Digit Vigilance)
Timepoint [1] 323115 0
After administration of treatment. Specifically, this will occur at 30 minutes post-dosing and at 2.5 hours post dosing. This will be assessed using the CogTrack online test battery.
Primary outcome [2] 323116 0
Associations between acute dose of Methylphenidate (Ritalin) 10mg and driving performance
Timepoint [2] 323116 0
After administration of treatment. Specifically, this will occur at ~2 hours post dosing. This will be assessed using the Forum 8 driving simulator. Weaving of the car, expressed as standard deviation of the lateral position (SDLP) will be assessed.
Primary outcome [3] 323117 0
Evaluate the efficacy of co-monitoring eye movement activity to identify driving impairment caused by consumption of Methylphenidate (Ritalin)
Timepoint [3] 323117 0
After administration of treatment. Specifically, this will occur at approximately 1.5 hours post dosing in conjunction with the driving simulator task. This will be assessed using the Sensometrics cap-mounted eye tracking system and will measure saccade
Secondary outcome [1] 380847 0
Associations between Methylpheniate (Ritalin) and cognitive performance (spatial working memory) PRIMARY OUTCOME
Timepoint [1] 380847 0
After administration of treatment. Specifically, this will occur at 30 minutes post-dosing and at 2.5 hours post dosing. This will be assessed using the CogTrack online test battery
Secondary outcome [2] 381359 0
Associations between Methylpheniate (Ritalin) and cognitive performance (numeric working memory ) PRIMARY OUTCOME
Timepoint [2] 381359 0
After administration of treatment. Specifically, this will occur at 30 minutes post-dosing and at 2.5 hours post dosing. This will be assessed using the CogTrack online test battery
Secondary outcome [3] 381361 0
Associations between Methylpheniate (Ritalin) and cognitive performance [reaction time (simple and complex)] PRIMARY OUTCOME
Timepoint [3] 381361 0
After administration of treatment. Specifically, this will occur at 30 minutes post-dosing and at 2.5 hours post dosing. This will be assessed using the CogTrack online test battery

Secondary outcome [4] 381362 0
Associations between acute dose of Methylphenidate (Ritalin) 10mg and driving performance. Standard Deviation of Speed (SDS) will be assessed
Timepoint [4] 381362 0
After administration of treatment. Specifically, this will occur at 1.5 hours post dosing. This will be assessed using the Forum 8 driving simulator. Standard Deviation of Speed (SDS) will be assessed
Secondary outcome [5] 381363 0
Associations between acute dose of Methylphenidate (Ritalin) 10mg and driving performance. Number of lapses will be assessed
Timepoint [5] 381363 0
After administration of treatment. Specifically, this will occur at 1.5 hours post dosing. This will be assessed using the Forum 8 driving simulator. Number of lapses will be assessed
Secondary outcome [6] 381365 0
Evaluate the efficacy of co-monitoring eye movement activity to identify driving impairment caused by consumption of Methylphenidate (Ritalin) (PRIMARY OUTCOME). This will be assessed using the Sensometrics cap-mounted eye tracking system and will measure blink parameters (blink amplitude)..
Timepoint [6] 381365 0
After administration of treatment. Specifically, this will occur at ~1.5 hours post dosing in conjunction with the driving simulator task. This will be assessed using the Sensometrics cap-mounted eye tracking system and will measure blink parameters (blink amplitude).
Secondary outcome [7] 381368 0
Associations between Methylphenidate (Ritalin) and performance on a visuospatial working memory task (VSWM)
Timepoint [7] 381368 0
After administration of treatment. Specifically, this will occur at approximately 50 minutes and at approximately 2 hours 45 minutes hours post dosing.
Secondary outcome [8] 381369 0
To identify the effect of Methylphenidate (Ritalin) 10mg dose on state behavioural aggression
Timepoint [8] 381369 0
After administration of treatment. Specifically, this will occur at approximately 1 hour post dosing using the Point Subtraction Aggression Paradigm task (PSAP).
Secondary outcome [9] 381370 0
To identify how trait impulsivity influences performance on the VSWM task following dosing with Methylphenidate (Ritalin) 10mg dose
Timepoint [9] 381370 0
Trait impulsivity will be measured at the screening visit (V0) using the UPPS-P Impulsivity Scale). VSWM performance will be measured using a visuospatial working memory task and will be assessed at approximately 50 minutes and at approximately 2 hours 45 minutes hours post dosing.
Secondary outcome [10] 381371 0
To identify how trait aggression influences performance on the neurocognitve tasks (Cogtrack) following dosing with Methylphenidate (Ritalin) 10mg dose
Timepoint [10] 381371 0
At screening visit (V0), after informed consent has been obtained and the participant has been screened for inclusion/exclusion criteria. Specifically, this will occur using the NEO Five-Factor Inventory-3 .

Neurocognitive tasks (Cogtrack) will be assessed at approximately 2 hours 45 minutes hours post-dosing during the active treatment sessions..
Secondary outcome [11] 381373 0
To identify the effect of Methylphenidate (Ritalin) 10mg dose on objective sleep parameters The outcome to be assessed is: sleep duration (total sleep time, hours)
Timepoint [11] 381373 0
On conclusion of the testing session and for the one-week wash-out period between sessions using a wrist-mounted actigraphy device
Secondary outcome [12] 381374 0
To identify the effect of Methylphenidate (Ritalin) 10mg dose on objective sleep parameters. The outcome to be assessed is: sleep latency (time to get to sleep)
Timepoint [12] 381374 0
On conclusion of the testing session and for the one-week wash-out period between sessions using a wrist-mounted actigraphy device
Secondary outcome [13] 381375 0
To identify the effect of Methylphenidate (Ritalin) 10mg dose on objective sleep parameters. The outcome to be assessed is: number of awakenings
Timepoint [13] 381375 0
On conclusion of the testing session and for the one-week wash-out period between sessions using a wrist-mounted actigraphy device
Secondary outcome [14] 381815 0
To identify the effect of Methylphenidate (Ritalin) 10mg dose on subjective drug effects
Timepoint [14] 381815 0
After administration of treatment. Specifically, this will occur at approximately 30 minutes, 50 minutes, 2 hours and 2.5 hours post dosing using a subjective questionnaire. The question is 'How STRONG of a drug effect are you feeling right now?' and participants are required to indicate one of four response options:
- Very strong effect
- Moderately strong effect
- Definite mild effect
- Possible mild effect
- No drug effect at all
Secondary outcome [15] 381816 0
To identify the effect of Methylphenidate (Ritalin) 10mg dose on subjective drug effects
Timepoint [15] 381816 0
After administration of treatment. Specifically, this will occur at approximately 30 minutes, 50 minutes, 2 hours and 2.5 hours post dosing using a subjective questionnaire. The question is 'Do you feel any “GOOD EFFECTS” from the drug?' and participants are required to indicate one of four response options:
-Very much
- Quite a bit
- Moderately
- A little
- No good effects at all
Secondary outcome [16] 381817 0
To identify the effect of Methylphenidate (Ritalin) 10mg dose on subjective drug effects
Timepoint [16] 381817 0
After administration of treatment. Specifically, this will occur at approximately 30 minutes, 50 minutes, 2 hours and 2.5 hours post dosing using a subjective questionnaire. The question is 'Do you feel any “BAD EFFECTS” from the drug?' and participants are required to indicate one of four response options:
-Very much
- Quite a bit
- Moderately
- A little
- No bad effects at all
Secondary outcome [17] 381818 0
To identify the effect of Methylphenidate (Ritalin) 10mg dose on subjective drug effects
Timepoint [17] 381818 0
After administration of treatment. Specifically, this will occur at approximately 30 minutes, 50 minutes, 2 hours and 2.5 hours post dosing using a subjective questionnaire. The question is 'Rate the degree to which you would be willing to take today’s drug again.' and participants are required to indicate one of four response options:
-Very much
- Quite a bit
- Moderately
- A little
- Not at all
Secondary outcome [18] 381819 0
To identify the effect of Methylphenidate (Ritalin) 10mg dose on subjective drug effects
Timepoint [18] 381819 0
After administration of treatment. Specifically, this will occur at approximately 30 minutes, 50 minutes, 2 hours and 2.5 hours post dosing using a subjective questionnaire. The question is 'Do you LIKE the way the drug makes you feel right now?.' and participants are required to indicate one of four response options:
- Like very much
- Like quite a bit
- Like somewhat
- Like, but not very much
- Feel neutral or no drug effect
- Dislike, but not very much
- Dislike somewhat
- Dislike quite a bit
- Dislike very much
Secondary outcome [19] 381820 0
To identify the effect of Methylphenidate (Ritalin) 10mg dose on subjective drug effects
Timepoint [19] 381820 0
After administration of treatment. Specifically, this will occur at approximately 30 minutes, 50 minutes, 2 hours and 2.5 hours post dosing using a subjective questionnaire. The question is 'Which one of the drugs listed below is the drug effect most like?.' and participants are required to indicate one of four response options:
- Stimulant
- Placebo
Secondary outcome [20] 381822 0
Evaluate the efficacy of co-monitoring eye movement activity to identify driving impairment caused by consumption of Methylphenidate (Ritalin) (PRIMARY OUTCOME). This will be assessed using the Sensometrics cap-mounted eye tracking system and will measure blink parameters (blink velocity).
Timepoint [20] 381822 0
After administration of treatment. Specifically, this will occur at ~1.5 hours post dosing in conjunction with the driving simulator task. This will be assessed using the Sensometrics cap-mounted eye tracking system and will measure blink parameters (blink velocity).
Secondary outcome [21] 381823 0
Evaluate the efficacy of co-monitoring eye movement activity to identify driving impairment caused by consumption of Methylphenidate (Ritalin) (PRIMARY OUTCOME). This will be assessed using the Sensometrics cap-mounted eye tracking system and will measure blink parameters (blink duration).
Timepoint [21] 381823 0
After administration of treatment. Specifically, this will occur at ~1.5 hours post dosing in conjunction with the driving simulator task. This will be assessed using the Sensometrics cap-mounted eye tracking system and will measure blink parameters (blink duration).
Secondary outcome [22] 381824 0
dentify associations between whole blood concentrations of methylphenidate on cognitive, driving, aggression and sleep outcomes
Timepoint [22] 381824 0
After administration of treatment using a single-draw procedure. Specifically, this will occur at approximately 3 hours post-dosing.

Eligibility
Key inclusion criteria
• Male or female, aged 21 to 45 years;
• Less than 100kg in weight [due to expected metabolism rate of Methylphenidate (Ritalin®), 10mg];
• Willing and able to provide written informed consent;
• Understands and is willing and able to comply with all study procedures;
• Fluent in written and spoken English;
• Must have normal or corrected-to-normal vision;
• Is a regular driver (> 4,000 km/year) with three years of driving with a full driver’s licence;
• Willing to abstain from the following prior to their scheduled visit:
o No food or drinks (except water) within 2 hours prior to testing;
o No caffeine-containing products within 12 hours prior to testing;
o No alcohol within 24 hours prior to testing;
o No medication for at least 1 week prior to testing (except for prophylactic antibiotics, contraceptive pill or other routine medications to treat benign conditions, such as antibiotics to treat acne);
o No illicit substance use for one week prior to, and for the duration of the trial.
o No driving or riding a bicycle or motorbike from the testing site;
o No driving, riding, operating heavy machinery for 24 hours after leaving the site
o No alcohol, drugs, or medication (unless consulted with doctor) for 24 hours after
leaving the site.
Minimum age
21 Years
Maximum age
45 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
• Unable to understand or comply with testing procedures;
• Inability to speak or read English;
• History of drug or substance abuse or current illicit drug abuse;
• History of neurological conditions or previous or current history of psychiatric, cardiac, endocrine, gastrointestinal, or bleeding disorders;
• Pregnant, potentially pregnant or lactating;
• Taking any form of ongoing medication (except for prophylactic antibiotics, contraceptive pill or other routine medications to treat benign conditions, such as antibiotics to treat acne);
• Unable to participate in scheduled visit, treatment plan, tests and other study procedures according to the protocol;
• Current participation in any other studies involving investigational or marketed products within 30 days prior to the screening visit;
• Have previously participated in this study
• Currently under administrative or legal supervision.

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)
Blinding will be achieved by enlisting a disinterested third-party to code the treatments, and maintain the key to this code until data collection is completed.

The study treatment capsules will be delivered to the Principal Investigator in a sealed white plastic bottle, labelled with the name of the drug in capital letters and either the letter “A” or “B” to signify the blinded drug randomisation group.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation of the order of treatment visits will be determined by random allocation by a disinterested third party. All consenting participants will be assigned a participant number. The randomisation order that has been placed next to the participants’ number will be the allocated treatment order for that individual using publicly available randomisation software (Research Randomiser Software Version 4.0).

Randomisation codes will be kept in a sealed envelope in a locked filing cabinet. Although study investigators will know the location of, and have access to, the sealed envelope, they will not access it during data collection and data screening procedures. Access will only occur in the case of an emergency when the participant’s allocated treatment needs to be known. If this occurs, the ethics committee will be informed.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Crossover
Other design features
Phase
Phase 2
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Demographic data will be presented with summary statistics (number of participants, mean, standard deviation, median and range for variables) for each study. A mixed model ANOVA will be used to assess differences in neurocognitive and driving performance variables between the treatment group (methylphenidate placebo, active) for each condition. Post hoc comparisons will be undertaken where significant condition or interaction effects are observed to determine the significance of differences between groups as a function of treatment group.

Correlations between personality/mood measures, cognitive outcomes, performance on the gambling task and the driving simulator across time points as function of treatment group will be conducted using Pearson product moment coefficient r. The predictive ability of performance on cognitive outcome to performance on the driving simulator task will be assessed using linear regression models.
Linear regression models will be used to assess associations between whole blood concentrations of methylphenidate and performance on target CANTAB and driving simulator variables.
All statistical analyses will be conducted with the use of SPSS 24.0 (SPSS Inc., USA), and tests are two-tailed with a conventional level of significance of p< 0.05.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
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)
VIC

Funding & Sponsors
Funding source category [1] 305151 0
University
Name [1] 305151 0
Swinburne University of Technology
Address [1] 305151 0
427-451 Burwood Road
Hawthorn, Victoria, 3122
Country [1] 305151 0
Australia
Primary sponsor type
University
Name
Swinburne University of Technology
Address
427-451 Burwood Road
Hawthorn, Victoria, 3122
Country
Australia
Secondary sponsor category [1] 305681 0
None
Name [1] 305681 0
Address [1] 305681 0
Country [1] 305681 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 305517 0
Swinburne University Human Research Ethics
Ethics committee address [1] 305517 0
Research Ethics Officer,
Swinburne Research (H68),
Swinburne University of Technology,
P O Box 218,
Hawthorn, Victoria, 3122.
Ethics committee country [1] 305517 0
Australia
Date submitted for ethics approval [1] 305517 0
11/03/2020
Approval date [1] 305517 0
08/04/2020
Ethics approval number [1] 305517 0
20202839-3910

Summary
Brief summary
This research thus aims to address these gaps in knowledge and practice by characterising how acute doses of Methylphenidate (Ritalin) affect ocular parameters and the visual attentional system. Furthermore, we seek to examine how these changes might be indexed to predict impairment in performance during a neurocognitive and driving task.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 100642 0
Dr Amie Hayley
Address 100642 0
Swinburne University of Technology,
Faculty of Health, Arts and Design
School of Health Sciences
Centre for Human Psychopharmacology
Mail H24
PO Box 218
Hawthorn, Victoria, 3122
Country 100642 0
Australia
Phone 100642 0
+61 3 92145585
Fax 100642 0
Email 100642 0
ahayley@swin.edu.au
Contact person for public queries
Name 100643 0
Dr Amie Hayley
Address 100643 0
Swinburne University of Technology,
Faculty of Health, Arts and Design
School of Health Sciences
Centre for Human Psychopharmacology
Mail H24
PO Box 218
Hawthorn, Victoria, 3122
Country 100643 0
Australia
Phone 100643 0
+61 3 92145585
Fax 100643 0
Email 100643 0
ahayley@swin.edu.au
Contact person for scientific queries
Name 100644 0
Dr Amie Hayley
Address 100644 0
Swinburne University of Technology,
Faculty of Health, Arts and Design
School of Health Sciences
Centre for Human Psychopharmacology
Mail H24
PO Box 218
Hawthorn, Victoria, 3122
Country 100644 0
Australia
Phone 100644 0
+61 3 92145585
Fax 100644 0
Email 100644 0
ahayley@swin.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
This will be discussed with the research team prior to disclosure
What supporting documents are/will be available?
No other documents available
Summary results
No Results