CompletedPhase 1ACTRN12614000046606

The link between impulsivity and dopamine

The relationship between cognitive-motor impulsivity, dopaminergic genotype and dopamine agonist medication in healthy individuals


Sponsor

Professor Winston Byblow

Enrollment

60 participants

Start Date

Feb 1, 2014

Study Type

Interventional

Conditions

Summary

Dopamine agonist medications are commonly prescribed to alleviate Parkinson’s disease symptoms and avoid some of the problems associated with levodopa medication. However, about one in five patients (20 %) prescribed dopamine agonist medications for Parkinson’s disease develop impulse control disorders. This project will evaluate tests to measure impulse control. We propose that when such measures are combined with information about a person’s dopamine gene profile, this knowledge can be used to identify individuals at risk of an adverse response to dopamine agonist medication. This could lead to better individualised treatment of Parkinson’s disease.


Eligibility

Sex: Both males and femalesMin Age: 40 YearssMax Age: 75 Yearss

Inclusion Criteria3

  • Between 40 and 75 years of age.
  • No neurological disease or disorder.
  • Normal or corrected to normal vision.

Exclusion Criteria1

  • 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.

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Interventions

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. Duri

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.


Locations(1)

New Zealand

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ACTRN12614000046606