Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12617001544369
Ethics application status
Approved
Date submitted
27/10/2017
Date registered
7/11/2017
Date last updated
11/10/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Pharmaceutical enhancement of complex problem-solving in healthy adults
Scientific title
Effect of pharmaceutical dopaminergic enhancement on performance in a complex optimisation task in healthy adults
Secondary ID [1] 293232 0
CT-2017-CTN-04278-1 (Therapeutic Goods Administration, Australia)
Universal Trial Number (UTN)
U1111-1204-3404
Trial acronym
PECO
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cognitive enhancement 305269 0
Condition category
Condition code
Mental Health 304578 304578 0 0
Studies of normal psychology, cognitive function and behaviour
Neurological 304582 304582 0 0
Studies of the normal brain and nervous system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
A single oral dose of a capsule containing 15 milligrams dextroamphetamine, 30 milligrams of methylphenidate, 200 milligrams of modafinil or placebo prior to cognitive testing in a repeated-measures full crossover double-blinded design in healthy volunteers. A washout period of at least seven days will be observed between testing sessions. Cognitive testing commences 90 minutes after dosage, and includes solving complex optimisation problems, spatial working memory tests, motor inhibition tests, reaction time and spatial problem solving. Cognitive testing will take between 60 and 90 minutes, depending on the speed of the individual participant.
Intervention code [1] 299488 0
Treatment: Drugs
Comparator / control treatment
This is a placebo-controlled, double-blinded full-crossover repeated-measures design. Placebo will be microcellulose (Avicel) capsule.
Control group
Placebo

Outcomes
Primary outcome [1] 303798 0
Performance in complex optimisation task as measured by accuracy scores. That is, are the items selected by the participant included in the optimal solution. This is also referred to as "computational perfomance".
Timepoint [1] 303798 0
Tasks will be administered 90 minutes after drug administration, and completed by 180 minutes after drug administration. This outcome will be assessed for each drug administration.
Secondary outcome [1] 340197 0
Network analysis of the steps taken to solve the complex optimisation tasks. That is, analysis of which items are selected and deselected as the participant attempts to maximise ("optimise") the solution to the problem. This sequence of selection and deselection of items can be visualised in "decision space" and the number of steps taken to achieve a solution can be analysed.
Timepoint [1] 340197 0
Tasks will be administered 90 minutes after drug administration, and completed by 180 minutes after drug administration. This outcome will be assessed for each drug administration.
Secondary outcome [2] 340243 0
"Economic performance" of the complex optimisation task, that is, how close the submitted solution is to the known optimal solution.
Timepoint [2] 340243 0
Tasks will be administered 90 minutes after drug administration, and completed by 180 minutes after drug administration. This outcome will be assessed for each drug administration.
Secondary outcome [3] 340244 0
Spatial working memory performance, as measured by error rate on the CANTAB spatial working memory task.
Timepoint [3] 340244 0
Tasks will be administered 90 minutes after drug administration, and completed by 180 minutes after drug administration. This outcome will be assessed for each drug administration.
Secondary outcome [4] 340245 0
Motor inhibition, as measured by error rate on the CANTAB stop-signal task.
Timepoint [4] 340245 0
Tasks will be administered 90 minutes after drug administration, and completed by 180 minutes after drug administration. This outcome will be assessed for each drug administration.
Secondary outcome [5] 340246 0
Reaction time, as measured on the CANTAB reaction time task.
Timepoint [5] 340246 0
Tasks will be administered 90 minutes after drug administration, and completed by 180 minutes after drug administration. This outcome will be assessed for each drug administration.
Secondary outcome [6] 340247 0
Spatial problem solving, as measured by accuracy rate on the CANTAB stockings of Cambridge task.
Timepoint [6] 340247 0
Tasks will be administered 90 minutes after drug administration, and completed by 180 minutes after drug administration. This outcome will be assessed for each drug administration.

Eligibility
Key inclusion criteria
Healthy volunteers aged between 18 and 35 years old.
Minimum age
18 Years
Maximum age
35 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
History of psychiatric or neurological illness including epilepsy, head injury, previous use of psychotropic medication, history of significant drug use, heart conditions (including high blood pressure, defined as above 140 mm/Hg systolic and/or 90 mm/Hg diastolic pressure as measured at the initial assessment session) pregnancy, or glaucoma. Any family history of sudden death of a first degree relative through cardiac or unknown causes before the age of 50 years old will also exclude the participant.

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)
Sealed opaque envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by
computer software.
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 4
Type of endpoint/s
Efficacy
Statistical methods / analysis
Power calculations performed with G*Power found that for a repeated-measures within-factors ANOVA with one group and four measurements, an estimated within-participants correlation of 0.5 and an eta squared of 0.2 (equivalent effect size 0.5) the calculated total minimum sample size is 10 and the critical F score is 2.69. For a within-between interaction, the minimum sample size would be 12, and critical F score 2.92. If the correlation is changed to 0.1 the total minimum sample size is 17, and the critical F score is 2.798. For a within-between interaction, the minimum sample size would be 18, and critical F score 2.798. When the alpha error probability is reduced from 0.05 to 0.0167 to allow for the repeated
comparisons between the three medication conditions and placebo, the corresponding total sample sizes are 13, 14, 21 and 22 participants. This project proposes a total sample size of 32 participants.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
24/11/2017
Actual
24/11/2017
Date of last participant enrolment
Anticipated
31/01/2018
Actual
30/07/2018
Date of last data collection
Anticipated
30/04/2018
Actual
14/09/2018
Sample size
Target
32
Accrual to date
Final
42
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 297862 0
University
Name [1] 297862 0
The University of Melbourne
Country [1] 297862 0
Australia
Primary sponsor type
University
Name
The University of Melbourne
Address
The University of Melbourne
Victoria 3010
Country
Australia
Secondary sponsor category [1] 296902 0
None
Name [1] 296902 0
Address [1] 296902 0
Country [1] 296902 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298911 0
University of Melbourne Health Sciences Human Ethics Sub-Committee
Ethics committee address [1] 298911 0
Research Ethics & Integrity
Level 1, 21 Bedford St, North Melbourne
The University of Melbourne
VIC 3051
Ethics committee country [1] 298911 0
Australia
Date submitted for ethics approval [1] 298911 0
15/08/2017
Approval date [1] 298911 0
22/09/2017
Ethics approval number [1] 298911 0
1749142

Summary
Brief summary
A) Aims and Objectives
This project aims to investigate the role of the neurotransmitter dopamine in complex decision making, and how three prescription stimulant medications that modulate dopamine levels in the brain in slightly different ways can affect the quality of complex decision making. These medications (dextroamphetamine, methylphenidate and modafinil) are increasingly used by healthy people for non-medical, cognitive enhancement purposes, however their effects on basic cognition are often found to be inconsistent, and their effects on more naturalistic, complex optimisation behaviours are not known.
B) Key Question(s)
Do stimulant medications, that increase dopamine in the brain, enhance, or have a deleterious effect, on the completion of a complex decision making task. More specifically do they;
* Affect the amount of time taken to solve a problem?
* Increase or decrease the likelihood that a participant will find the correct solution to the problem (the computational performance)?
* Increase or decrease the computational distance between the participant’s solution and the correct solution (the economic performance)?
* Affect the variety of search paths that participants take through the space of possible solutions?

C) Research Design
This study will utilize a double-blinded placebo-controlled crossover design. We will recruit 32 healthy participants with no history of neurological, psychiatric or heart conditions. Each one will participate in an initial assessment session and four testing sessions, each at least one week apart to allow for pharmaceutical washout. At each session, the participant will receive either a single dose of the three pharmaceuticals or the placebo. After a 90-minute waiting period, during which the participant fills out number of demographic and personality surveys, the participant will complete a series of computerised complex optimisation tasks and basic cognition tasks. Data collected includes the sequence and timing of the selection of items for each task solution, key variables from the more basic cognitive tasks and the answers to the survey questions.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 78622 0
Prof David Coghill
Address 78622 0
Departments of Paediatrics and Psychiatry
The University of Melbourne
Professor of Child and Adolescent Psychiatry,
The Royal Children’s Hospital,
50 Flemington Road,
Parkville, Victoria, 3052
Country 78622 0
Australia
Phone 78622 0
+61 3 9345 6856
Fax 78622 0
Email 78622 0
[email protected]
Contact person for public queries
Name 78623 0
Dr Elizabeth Bowman
Address 78623 0
Brain, Mind and Markets Laboratory
Department of Finance
The University of Melbourne
Victoria, 3010
Country 78623 0
Australia
Phone 78623 0
+61 3 9035 9950
Fax 78623 0
+61 3 8344 6914
Email 78623 0
[email protected]
Contact person for scientific queries
Name 78624 0
Dr Elizabeth Bowman
Address 78624 0
Brain, Mind and Markets Laboratory
Department of Finance
The University of Melbourne
Victoria, 3010
Country 78624 0
Australia
Phone 78624 0
+61 3 9035 9950
Fax 78624 0
+61 3 8344 6914
Email 78624 0
[email protected]

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Results publications and other study-related documents

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