Clinical trial NCT05169827: Cerebral Contributions to Symptom Progression in PD
Official title: How Cerebral Plasticity Shapes Symptom Progression in Parkinson's Disease: a Longitudinal Neuroimaging Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Parkinson Disease
Keywords: magnetic resonance imaging
motor assessment
symptom progression
action selection
compensation
basal ganglia
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
First posted: 2021-12-27
Enrollment: 115
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Any person with, or without, Parkinson's disease who meets the inclusion criteria and does not meet the exclusion criteria

Brief summary: Motor symptom progression in early-stage Parkinson's disease varies substantially between individual patients. This progression correlates poorly with striatal dopamine depletion, which is largely complete four years post-diagnosis. Identification of alternative mechanisms, such as cortical compensatory processes, may enable more accurate predictions of individual motor progression.

Detailed description: Striatal dopamine depletion leads to dysfunction in the cortico-striatal motor circuit and is an important contributor to motor symptoms in Parkinson's disease (PD). However, dopamine depletion in striatal motor regions is already severe at symptom onset and tends to correlate poorly with progressive worsening. This indicates that the severity of motor symptoms in PD may not be solely dependent on basal ganglia dysfunction. In PD, the deleterious effect of basal ganglia dysfunction on motor control may be partially counteracted by neuroplasticity and the compensatory recruitment of parieto-premotor areas of cortex that drive movement based on sensory cueing and goal-directed cognitive control. The efficacy of cortical compensation could therefore be a core determinant of motor impairment in PD.

This study utilizes longitudinal clinical and brain imaging data from early-stage PD patients included in the Personalized Parkinson Project (ClinicalTrials.gov Identifier: NCT03364894) to test whether motor symptom severity and progression can be predicted by action selection-related brain activity in parieto-premotor cortex, basal ganglia, or a combination of both.

Additional control analyses will be performed to investigate the effects of disease and medication on action selection-related brain activity. Action selection-related brain activity will be compared between PD patients and a cohort of healthy controls to assess the effect of disease (PD vs Healthy). Effects of medication (on vs. off) on action selection-related brain activity will be investigated through within-subject comparisons in subset of PD patients who underwent functional brain imaging in both on- and off-medicated states.

Eligibility criteria: Inclusion Criteria (patients):

* Subject is included in the Personalized Parkinson Project and has already participated in all baseline measurements (this means that inclusion and exclusion criteria of the Personalized Parkinson Project have already been fulfilled)
* Subject has completed the Informed Consent Form, as approved by the Ethics Committee

Exclusion Criteria (patients):

* Subject is not taking dopaminergic medication

Inclusion Criteria (healthy controls):

* Subject is at least 40 years old
* Subject can read and understand Dutch
* Subject has completed the Informed Consent Form, as approved by the Ethics Committee
* Subject is willing, competent, and able to comply with all aspects of the protocol, including follow-up schedule.

Exclusion Criteria (healthy controls):

* Subject has no co-morbidities that would negatively influence the interpretability of results from a comparison with PD patients (e.g. other neurodegenerative diseases or mental health disorders)

Primary outcomes:
measure: Mid-term disease progression in terms of overall motor symptoms
timeFrame: Baseline and 2 years
measure: Mid-term disease progression in terms of bradykinesia and rigidity
timeFrame: Baseline and 2 years
Secondary outcomes:
Other outcomes:
Locations:
city: Nijmegen
country: Netherlands
facility: Donders institute for brain, cognition and behaviour
state: Gelderland
Study officials:
affiliation: Donders Centre for Cognitive Neuroimaging
name: Rick C Helmich, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Radboud University Medical Center, Department of Neurology
name: Bastiaan R Bloem, MD, PhD
role: PRINCIPAL_INVESTIGATOR
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