Cerebral Contributions to Symptom Progression in PD

December 8, 2021 updated by: Radboud University Medical Center

How Cerebral Plasticity Shapes Symptom Progression in Parkinson's Disease: A Longitudinal Neuroimaging Study

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.

Study Overview

Status

Active, not recruiting

Conditions

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.

Study Type

Observational

Enrollment (Actual)

115

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
    • Gelderland
      • Nijmegen, Gelderland, Netherlands, 6500HB
        • Donders Institute for Brain, Cognition and Behaviour

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

40 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

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

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Control
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
PD-OFF

Patients with PD who have previously been included in the Personalized Parkinson Project return for fMRI measurements in an off-medicated state (12h withdrawal). N = 60.

The PD-OFF group undergoes a single testing session.
Healthy controls

Healthy individuals who are matched on age and sex with respect to the PD-OFF group. N = 60.

The healthy group undergoes baseline and two year follow-up testing sessions.
PD-ON

Patients with PD who are included in the Personalized Parkinson Project. N = 360.

Available data will be used. There will be no further data collection in this group.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mid-term disease progression in terms of overall motor symptoms
Time Frame: Baseline and 2 years
Change in Movement Disorders Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III score, measured in off state. This scale assesses 18 motor symptoms (33 items) that are specific for Parkinson's disease. Item scores range from 0 to 4 and are summed, resulting in a total score ranging from 0 to 132, with higher scores representing worse outcomes.
Baseline and 2 years
Mid-term disease progression in terms of bradykinesia and rigidity
Time Frame: Baseline and 2 years
Change in Movement Disorders Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III score, measured in off state. This scale assesses 18 motor symptoms (33 items) that are specific for Parkinson's disease. Item scores range from 0 to 4. 17 items assessing bradykinesia and rigidity and are summed, resulting in a total score ranging from 0 to 68, with higher scores representing worse outcomes.
Baseline and 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Radboud University Medical Center

Investigators

  • Principal Investigator: Rick C Helmich, MD, PhD, Donders Centre for Cognitive Neuroimaging
  • Principal Investigator: Bastiaan R Bloem, MD, PhD, Radboud University Medical Center, Department of Neurology

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 1, 2019

Primary Completion (Anticipated)

December 1, 2022

Study Completion (Anticipated)

December 1, 2022

Study Registration Dates

First Submitted

March 30, 2021

First Submitted That Met QC Criteria

December 8, 2021

First Posted (Actual)

December 27, 2021

Study Record Updates

Last Update Posted (Actual)

December 27, 2021

Last Update Submitted That Met QC Criteria

December 8, 2021

Last Verified

December 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NL67597.091.18

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

See plan description for the Personalized Parkinson Project.

In addition to these steps, we will make our statistical analysis plan and analytic code available to researchers that specifically focus on data related to the action selection task.

IPD Sharing Time Frame

TBA.

IPD Sharing Access Criteria

Currently no list of criteria is available.

IPD Sharing Supporting Information Type

  • Study Protocol
  • Statistical Analysis Plan (SAP)
  • Analytic Code

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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