Cerebral Contributions to Symptom Progression in PD

NCT ID: NCT05169827

Last Updated: 2025-02-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

115 participants

Study Classification

OBSERVATIONAL

Study Start Date

2019-12-01

Study Completion Date

2023-11-28

Brief Summary

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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

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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.

Conditions

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Parkinson Disease

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

PROSPECTIVE

Study Groups

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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.

No interventions assigned to this group

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.

No interventions assigned to this group

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.

No interventions assigned to this group

Eligibility Criteria

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Inclusion Criteria

* 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

* Subject has completed the Informed Consent Form, as approved by the Ethics Committee


* Subject is not taking dopaminergic medication


* 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)
Minimum Eligible Age

40 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Radboud University Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Rick C Helmich, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Donders Centre for Cognitive Neuroimaging

Bastiaan R Bloem, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Radboud University Medical Center, Department of Neurology

Locations

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Donders institute for brain, cognition and behaviour

Nijmegen, Gelderland, Netherlands

Site Status

Countries

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Netherlands

References

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Buhmann C, Binkofski F, Klein C, Buchel C, van Eimeren T, Erdmann C, Hedrich K, Kasten M, Hagenah J, Deuschl G, Pramstaller PP, Siebner HR. Motor reorganization in asymptomatic carriers of a single mutant Parkin allele: a human model for presymptomatic parkinsonism. Brain. 2005 Oct;128(Pt 10):2281-90. doi: 10.1093/brain/awh572. Epub 2005 Jun 9.

Reference Type BACKGROUND
PMID: 15947065 (View on PubMed)

Helmich RC, de Lange FP, Bloem BR, Toni I. Cerebral compensation during motor imagery in Parkinson's disease. Neuropsychologia. 2007 Jun 11;45(10):2201-15. doi: 10.1016/j.neuropsychologia.2007.02.024. Epub 2007 Mar 7.

Reference Type BACKGROUND
PMID: 17448507 (View on PubMed)

Herz DM, Eickhoff SB, Lokkegaard A, Siebner HR. Functional neuroimaging of motor control in Parkinson's disease: a meta-analysis. Hum Brain Mapp. 2014 Jul;35(7):3227-37. doi: 10.1002/hbm.22397. Epub 2013 Oct 5.

Reference Type BACKGROUND
PMID: 24123553 (View on PubMed)

Herz DM, Meder D, Camilleri JA, Eickhoff SB, Siebner HR. Brain Motor Network Changes in Parkinson's Disease: Evidence from Meta-Analytic Modeling. Mov Disord. 2021 May;36(5):1180-1190. doi: 10.1002/mds.28468. Epub 2021 Jan 11.

Reference Type BACKGROUND
PMID: 33427336 (View on PubMed)

Kordower JH, Olanow CW, Dodiya HB, Chu Y, Beach TG, Adler CH, Halliday GM, Bartus RT. Disease duration and the integrity of the nigrostriatal system in Parkinson's disease. Brain. 2013 Aug;136(Pt 8):2419-31. doi: 10.1093/brain/awt192.

Reference Type BACKGROUND
PMID: 23884810 (View on PubMed)

Michely J, Volz LJ, Barbe MT, Hoffstaedter F, Viswanathan S, Timmermann L, Eickhoff SB, Fink GR, Grefkes C. Dopaminergic modulation of motor network dynamics in Parkinson's disease. Brain. 2015 Mar;138(Pt 3):664-78. doi: 10.1093/brain/awu381. Epub 2015 Jan 6.

Reference Type BACKGROUND
PMID: 25567321 (View on PubMed)

van Nuenen BF, Helmich RC, Buenen N, van de Warrenburg BP, Bloem BR, Toni I. Compensatory activity in the extrastriate body area of Parkinson's disease patients. J Neurosci. 2012 Jul 11;32(28):9546-53. doi: 10.1523/JNEUROSCI.0335-12.2012.

Reference Type BACKGROUND
PMID: 22787040 (View on PubMed)

van Nuenen BF, van Eimeren T, van der Vegt JP, Buhmann C, Klein C, Bloem BR, Siebner HR. Mapping preclinical compensation in Parkinson's disease: an imaging genomics approach. Mov Disord. 2009;24 Suppl 2:S703-10. doi: 10.1002/mds.22635.

Reference Type BACKGROUND
PMID: 19877238 (View on PubMed)

Obeso JA, Rodriguez-Oroz MC, Rodriguez M, Lanciego JL, Artieda J, Gonzalo N, Olanow CW. Pathophysiology of the basal ganglia in Parkinson's disease. Trends Neurosci. 2000 Oct;23(10 Suppl):S8-19. doi: 10.1016/s1471-1931(00)00028-8.

Reference Type BACKGROUND
PMID: 11052215 (View on PubMed)

Palop JJ, Chin J, Mucke L. A network dysfunction perspective on neurodegenerative diseases. Nature. 2006 Oct 19;443(7113):768-73. doi: 10.1038/nature05289.

Reference Type BACKGROUND
PMID: 17051202 (View on PubMed)

Pirker W, Holler I, Gerschlager W, Asenbaum S, Zettinig G, Brucke T. Measuring the rate of progression of Parkinson's disease over a 5-year period with beta-CIT SPECT. Mov Disord. 2003 Nov;18(11):1266-72. doi: 10.1002/mds.10531.

Reference Type BACKGROUND
PMID: 14639666 (View on PubMed)

Redgrave P, Rodriguez M, Smith Y, Rodriguez-Oroz MC, Lehericy S, Bergman H, Agid Y, DeLong MR, Obeso JA. Goal-directed and habitual control in the basal ganglia: implications for Parkinson's disease. Nat Rev Neurosci. 2010 Nov;11(11):760-72. doi: 10.1038/nrn2915. Epub 2010 Oct 14.

Reference Type BACKGROUND
PMID: 20944662 (View on PubMed)

Related Links

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https://clinicaltrials.gov/ct2/show/NCT03364894?term=Personalized+Parkinson&draw=2&rank=1

Clinicaltrials.gov profile of the Personalized Parkinson Project

Other Identifiers

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NL67597.091.18

Identifier Type: -

Identifier Source: org_study_id

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