Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12614000046606
Ethics application status
Approved
Date submitted
8/01/2014
Date registered
17/01/2014
Date last updated
1/12/2020
Date data sharing statement initially provided
1/12/2020
Date results provided
1/12/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
The link between impulsivity and dopamine
Scientific title
The relationship between cognitive-motor impulsivity, dopaminergic genotype and dopamine agonist medication in healthy individuals
Secondary ID [1] 283865 0
None known
Universal Trial Number (UTN)
U1111-1150-6362
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Impulse control disorders in Parkinson's disease patients taking dopaminergic medication 290846 0
Condition category
Condition code
Neurological 291209 291209 0 0
Parkinson's disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This study involves 4 sessions: a single screening session (lasting up to 1 hour) and 3 experimental sessions (1 x 4 hour, 2 x 3 hour). Each experimental session will be spaced one week apart.

During the initial screening session all participants will be screened for cognitive function using the Montreal Cognitive Assessment (MoCA), screened for any contraindications to the medications, and will be assessed for parkinsonian symptoms using the Unified Parkinson's Disease Rating Scale (UPDRS, section 3). A blood sample for dopaminergic genotyping will be obtained from all participants.

Measures of impulsivity will be obtained using the Baratt Impulsiveness Scale (BSI-11), and depression using the Beck Depression Inventory (BDI).

Each participant will complete three experimental sessions: one session will be conducted after oral administration of domperidone (20mg) and 1 hour later oral administration of 0.5 mg of ropinirole, another after administration of 20mg domperidone and an hour later oral administration of 1.0 mg of ropinirole, and the third after administration of 20mg domperidone and an hour later oral administration of a placebo (dextrin) in a counterbalanced placebo-controlled double-blind design. During the first experimental session researchers will administer both the domperidone and ropinirole/placebo, so an additional hour is required between domperidone and ropinirole/placebo administration for this session. If no adverse reactions are seen, the participant will take domperidone themselves 1 hour before the second and third sessions, so these sessions begin with ropinirole/placebo administration and take 1 hour less (3 hours).

During each experimental session, the participants will complete the Central Nervous System Vital Signs (CNSVS) cognitive test battery, as well as performing cognitive (BART) and motor (Response Inhibition) computer-based impulse control tasks. Data collection will begin 1 hour after dosing of ropinirole, as this is when ropinirole reaches maximum plasma concentration and produces prominent effects in the central nervous system.

Each individual's dopamine gene score will be calculated from recording polymorphisms within the genes coding for the dopamine D1, D2 and D3 receptors, dopamine transporter and catechol-O-methyltransferase. Higher dopamine gene scores reflect greater levels of dopamine neurotransmission.
Intervention code [1] 288541 0
Early detection / Screening
Intervention code [2] 288591 0
Treatment: Drugs
Comparator / control treatment
Each participant will complete three experimental sessions: one session will be conducted after administration of domperidone and 0.5 mg of ropinirole, another after administration of domperidone and 1.0 mg of ropinirole, and the third after administration of domperidone and a placebo (dextrin) in a counterbalanced placebo-controlled double-blind design.
Control group
Placebo

Outcomes
Primary outcome [1] 291198 0
Stop signal reaction time in the Response Inhibition Task (motor impulse control).
Timepoint [1] 291198 0
1-2 hours after ropinirole administration.
Primary outcome [2] 291199 0
Number of responses in the Balloon Analogue Risk Task (cognitive impulse control).
Timepoint [2] 291199 0
1-2 hours after ropinirole administration.
Secondary outcome [1] 306225 0
EMG profile of responses in Response Inhibition Task.
Timepoint [1] 306225 0
1-2 hours after ropinirole administration.

Eligibility
Key inclusion criteria
Between 40 and 75 years of age.
No neurological disease or disorder.
Normal or corrected to normal vision.
Minimum age
40 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Cognitive impairment (MoCA score below 26); unable to provide informed consent; any contraindications to the medications or placebo. Contraindications include: a known hypersensitivity to ropinirole, domperidone, or any of the excipients; history of acute or chronic psychiatric disorder; history of severe cardiac, hepatic or renal disease; history of severe systemic disease; history of severe dizziness or fainting; a prolactin-releasing pituitary tumour; currently breast feeding; current tobacco smoking or nicotine patch; lactose intolerance; glucose/galactose malabsorption and any medications which may interact with ropinirole or domperidone, or themselves cause drowsiness.

Study design
Purpose of the study
Prevention
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation to group is not applicable - each participant will receive ropinirole and placebo. During each of the three experimental sessions, each participant will receive either 0.5 mg ropinirole, 1.0 mg ropinirole or placebo (dextrin). Allocation of drug or placebo will be done in a counterbalanced double-blind design. The researchers responsible for medication/placebo allocation will not be involved in data collection. The experimenter will choose from 3 pills labelled A, B or C for each session.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
There are 6 possible orders in which each participant can take the two doses of ropinirole and the single placebo. A random number generator will be used to select a discrete number from 1-6 for each participant when they are recruited, until there are a maximum of 10 participants for each order.
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 1
Type of endpoint/s
Efficacy
Statistical methods / analysis
60 participants will be recruited but it is assumed 50 will be included in the final analysis. Sample size accounts for drop out (about 8 people, 15 %) due to some participants being unable to adequately complete the response inhibition task or medication intolerance. We also require a sufficient sample size to capture the range of dopaminergic genotypes. E.g. For the COMT gene, in Caucasian populations, about 50% of the population are heterozygous (val/met), roughly 28% are homozygous for the met allele (met/met) and the remaining 22% are homozygous for the val allele (val/val). Furthermore, the frequency of the single nucleotide polymorphisms in the D2 (rs1800497) and D3 (rs6280) receptor genes in Caucasian populations is about 10 and 35 %, respectively.

A mixed effects regression model will be used to explore associations between an individual’s cognitive and motor measures of impulse control and dopamine gene score. We will model each impulse control measure (stop signal reaction time, number of balloon pumps) as a function of medication status (ropinirole vs placebo), weighted gene score and their interaction. Age, gender, weight and MoCA score will be controlled for by inclusion in the model as covariates. The effect on combined cognitive and motor measures of impulse control (reflected as an average z score) will also be modeled. an ANOVA will assess for a dose effect of ropinirole on cognitive and motor impulse control measures. Simple linear regression will be used to determine associations between impulse control measures and i) Baratt Impulsiveness and ii) Unified Parkinson's Disease Rating Scale scores. Hardy-Weinberg equilibrium of genotypes will be assessed using Chi squared tests.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/02/2014
Actual
1/02/2014
Date of last participant enrolment
Anticipated
Actual
31/12/2015
Date of last data collection
Anticipated
Actual
31/12/2015
Sample size
Target
60
Accrual to date
Final
33
Recruitment outside Australia
Country [1] 5724 0
New Zealand
State/province [1] 5724 0

Funding & Sponsors
Funding source category [1] 288511 0
Charities/Societies/Foundations
Name [1] 288511 0
Neurological Foundation of New Zealand
Country [1] 288511 0
New Zealand
Primary sponsor type
Individual
Name
Professor Winston Byblow
Address
Department of Exercise Sciences
The University of Auckland
Private Bag 92019
Auckland 1142
New Zealand
Country
New Zealand
Secondary sponsor category [1] 287217 0
None
Name [1] 287217 0
Address [1] 287217 0
Country [1] 287217 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 290374 0
Northern A Health and Disability Ethics Committee
Ethics committee address [1] 290374 0
Ethics committee country [1] 290374 0
New Zealand
Date submitted for ethics approval [1] 290374 0
Approval date [1] 290374 0
18/12/2013
Ethics approval number [1] 290374 0
13NTA215

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 45370 0
Prof Winston Byblow
Address 45370 0
Department of Sport and Exercise Science
The University of Auckland
Private Bag 92019
Auckland 1142
New Zealand
Country 45370 0
New Zealand
Phone 45370 0
+64 9 373 7599 extn 86844
Fax 45370 0
Email 45370 0
[email protected]
Contact person for public queries
Name 45371 0
Winston Byblow
Address 45371 0
Department of Sport and Exercise Science
The University of Auckland
Private Bag 92019
Auckland 1142
New Zealand
Country 45371 0
New Zealand
Phone 45371 0
+64 9 373 7599 extn 86844
Fax 45371 0
Email 45371 0
[email protected]
Contact person for scientific queries
Name 45372 0
Winston Byblow
Address 45372 0
Department of Sport and Exercise Science
The University of Auckland
Private Bag 92019
Auckland 1142
New Zealand
Country 45372 0
New Zealand
Phone 45372 0
+64 9 373 7599 extn 86844
Fax 45372 0
Email 45372 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


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
No additional documents have been identified.