To identify the cerebral mechanisms underlying clinical disease progression in PD. The current proposal aims to further specify: (1) differences in motor and limbic activity between patients and controls; (2) the effect of dopamine on motor and…
ID
Source
Brief title
Condition
- Movement disorders (incl parkinsonism)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
For this study, we will assess 50 patients with PD once (OFF their dopaminergic
medication) and 50 healthy volunteers twice (baseline and two-year follow up).
We will use a subset of the protocols used in the PPP, in which 650 PD patients
are assessed ON their dopaminergic medication. This protocol includes two
functional MRI tasks (motor task in first half (n=325) of patients, reward task
in second half (n=325) of patients) that quantify both (dysfunctional)
processing in the basal ganglia and (compensatory) processing in the cortex
(i.e. parietal cortex for the motor task, orbito-frontal cortex for the reward
task). We will quantify clinical disease progression with clinical measures
such as the MDS-UPDRS.
Secondary outcome
Secondary study parameters include participant characteristics (e.g. Age,
Gender, Comorbidity, Medication use), clinical measures (e.g. severity of
motor, cognitive and neuropsychiatric symptoms), and additional MRI-measures
(Resting state functional connectivity, Diffusion tensor imaging, Quantitative
susceptibility imaging and fluid-attenuated inversion recovery) to be used for
thorough interpretation of primary outcomes.
Background summary
Parkinson*s Disease (PD) is the second most prevalent degenerative brain
disease, with over 7 million people with PD worldwide. There is no cure, and
current treatments are unable to slow down disease progression. This is largely
caused by a lack of insight in the cerebral mechanisms underlying disease
progression. The pathological hallmark of PD is dopaminergic dysfunction of the
basal ganglia, but longitudinal studies show a surprisingly poor, if any,
correlation between worsening dopaminergic dysfunction and disease progression.
This suggests a key role for other, non-dopaminergic mechanisms outside the
basal ganglia. More specifically, we hypothesize that cerebral changes in
cortical regions inter-connected to the basal ganglia can compensate for
progressive basal ganglia dysfunction, and that the degree of cerebral
compensation is associated with inter-individual differences in disease
progression. We will focus on longitudinal changes across two distinct cerebral
circuits: the motor loop (associated with motoric symptoms) and the limbic loop
(associated with neuropsychiatric symptoms such as depression and apathy). This
study will build on the already approved and currently running Personalized
Parkinson Project (PPP, NL59694.091.16). To answer our research question, we
will add two crucial measurements to the existing PPP protocol: an additional
measurement OFF dopaminergic medication in a subsample of 50 PPP participants,
and two sessions (at baseline and after two years) in an additional group of 50
healthy controls.
Study objective
To identify the cerebral mechanisms underlying clinical disease progression in
PD. The current proposal aims to further specify: (1) differences in motor and
limbic activity between patients and controls; (2) the effect of dopamine on
motor and limbic activity in PD.
Study design
Combined cross-sectional and longitudinal observational study.
Study burden and risks
The load on patients consists of the time spent on this project, and
potentially a temporary worsening of symptoms caused by withholding medication.
Patients will arrive in a practically defined OFF state, i.e. at least 12 hours
after having taken their last dopaminergic medication. At the end of the
measurement, they will resume their normal medication regime. All measurements
are non-invasive, painless, and without nuclear radiation. Individual
participants do not directly benefit from participation. However, we expect
that this study will improve our knowledge about the cerebral mechanisms
underlying clinical disease progression in Parkinson*s disease (PD), which may
lead to new ways of treating this debilitating disease.
Kapittelweg 29
Nijmegen 6525 EN
NL
Kapittelweg 29
Nijmegen 6525 EN
NL
Listed location countries
Age
Inclusion criteria
General:
1) *40 years old.
2) Able to read and understand Dutch.
3) Subject is willing, competent, and able to comply with all aspects of the protocol, including
follow-up schedule.
Parkinson's Disease-specific:
1) Participation in motor and reward tasks Personalized Parkinson Project (NL59694.091.16)
2) Subject has Parkinson*s disease of *5 years* duration, defined as time since diagnosis made by a neurologist.
Exclusion criteria
1) Subject has co-morbidities that would hamper interpretation of parkinsonian disability or task performance, such as coincident musculoskeletal abnormalities, in the opinion of the investigator.
2) Contraindicated for MRI, e.g., claustrophobia, presence of an active implant, pacemaker, insulin pump, neurostimulator, ossicle prosthesis, pregnancy, and/or other medical device or other non-removable metal part incompatible with MRI.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL67597.091.18 |