We aim to develop a proxy-model of baseline dopamine based on machine learning methods which would provide us with behavioural predictors of the effects of dopaminergic drugs on brain and cognition that maximally generalize to new participants.
ID
Source
Brief title
Condition
- Cognitive and attention disorders and disturbances
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Baseline dopamine synthesis capacity measured with [18F]-DOPA PET; BOLD signal
measured with fMRI; behavioural performance on computerized tasks (measuring
reward sensitivity, working memory, reversal learning, reinforcement learning,
cognitive effort, the influence of affective information on goal-oriented
behaviour, and creativity); subjective measurements (e.g. self-report
questionnaires, visual analogue scales); psychophysiological recordings (e.g.,
blood pressure, heart rate, respiration, elctrocardiography); blood and saliva
sample to assess dopamine genes for pathway-based genetics analysis.
Secondary outcome
All tasks in the cognitive testing battery (computerized tasks) result in both
outcomes of primary interest (see section 7.1.1 in the study protocol) and
additional outcomes (see section 7.1.2 in the study protocol). Our secondary
objective is to further our understanding of the relationship between baseline
dopamine synthesis capacity and baseline measures - such as working memory,
genetic differences, impulsivity and eye-blink rate * to assess how baseline
levels of dopamine mediate the effects of the drug on the secondary outcomes
from the cognitive testing battery.
Background summary
Failures of cognitive control are common, not only in neuropsychiatric
disorders, but also in the healthy population. These failures can be remediated
with dopaminergic drugs, such as methylphenidate and sulpiride, but there is
huge individual variability in the direction and extent of dopaminergic drug
effects. Dopamine is known to play a role in many psychological functions, such
as cognitive control, learning, motivation and memory. However, at present our
ability to predict dopaminergic drug effects on behaviour across individuals
and different task demands is limited.
Study objective
We aim to develop a proxy-model of baseline dopamine based on machine learning
methods which would provide us with behavioural predictors of the effects of
dopaminergic drugs on brain and cognition that maximally generalize to new
participants.
Study design
A within-subject, double-blind, placebo-controlled cross-over design will be
employed. All subjects will visit the department of Radiology and Nuclear
Medicine of the Radboud UMC for one PET scan, and Donders center for cognitive
neuroimaging for one screening session and three pharmaco-fMRI testing
sessions. During the pharmaco-fMRI sessions subjects will receive oral capsules
of methylphenidate, sulpiride, and oral placebo capsules. In order for the fMRI
data acquisition to coincide with the time-window of maximal drug effects
represented by a combination of plasma kinetics and physiological effects we
will administrate the drugs at two different time points prior to fMRI data
acquisition by employing a double-dummy design. Thus, participants will receive
two capsules on two separate time points per test session. Participants will
receive placebo or methylphenidate ~80 minutes after receiving placebo or
sulpiride. Order of administration will depend on testing session:
sulpiride/placebo, placebo/methylphenidate and placebo/placebo. During the
visit at the department of Radiology and Nuclear Medicine of the Radboud UMC
all subjects will receive oral capsules of carbidopa and entacapone, and an
F-DOPA intravenous injection for PET acquisition.
Study burden and risks
Subjects will attend five study days; one screening session (3h), three
pharmaco-fMRI session (MPH, sulpiride and placebo; 6h each) and one session for
PET acquisition (carbidopa, entacapone and F-DOPA; 2.5h). Subjects will
complete a baseline battery measure, questionnaires, a structural MRI scan,
donate a saliva sample (2ml) and a blood sample (12.5ml) for pathway-based
genetics analysis, and complete a battery of computerized tests in and outside
of the fMRI scanner. On the day preceding a test session, subjects will have to
adhere to some simple restrictions with respect to medication, alcohol and drug
intake. On the day of testing subjects will have to refrain from smoking and
stimulant containing drinks. Methylphenidate, sulpiride, carbidopa, entacapone
and F-DOPA can be administered safely without any relevant risk of serious
adverse events and have been approved for clinical use in the Netherlands.
Kapittelweg 29
Nijmegen 6525 EN
NL
Kapittelweg 29
Nijmegen 6525 EN
NL
Listed location countries
Age
Inclusion criteria
Healthy volunteers between 18 and 45 years of age
Exclusion criteria
Neuropsychiatric disorders; history of drug abuse; heart problems; metal objects in or around the body (see section 4.3 in research protocol (C1) for full list of exclusion criteria)
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| CCMO | NL57538.091.16 |
| OMON | NL-OMON28994 |