Cerebral Contributions to Symptom Progression in PD

NCT05169827 | Completed

• 1 other identifier: NL67597.091.18
• Study Type: observational
• Target: 115
• Locations: 1 country
• Sites: 1

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.

Conditions

Parkinson Disease

Keywords

magnetic resonance imaging; motor assessment; symptom progression; action selection; compensation; basal ganglia

Outcome Measures

Primary Outcomes (2)

• Mid-term disease progression in terms of overall motor symptoms

  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

  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

Study Arms (3)

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.

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• 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

You may not qualify if:

• Subject has completed the Informed Consent Form, as approved by the Ethics Committee
• Subject is not taking dopaminergic medication
• 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.
• 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)

Sponsors & Collaborators

• Radboud University Medical Center: lead

Study Sites (1)

Donders institute for brain, cognition and behaviour

Nijmegen, Gelderland, 6500HB, Netherlands

Location

Related Publications (12)

• 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.

  PMID: 15947065 BACKGROUND

• 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.

  PMID: 17448507 BACKGROUND

• 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.

  PMID: 24123553 BACKGROUND

• 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.

  PMID: 33427336 BACKGROUND

• 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.

  PMID: 23884810 BACKGROUND

• 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.

  PMID: 25567321 BACKGROUND

• 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.

  PMID: 22787040 BACKGROUND

• 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.

  PMID: 19877238 BACKGROUND

• 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.

  PMID: 11052215 BACKGROUND

• 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.

  PMID: 17051202 BACKGROUND

• 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.

  PMID: 14639666 BACKGROUND

• 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.

  PMID: 20944662 BACKGROUND

Related Links

• Clinicaltrials.gov profile of the Personalized Parkinson Project

MeSH Terms

Conditions

Parkinson Disease

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Study Officials

• Rick C Helmich, MD, PhD

  Donders Centre for Cognitive Neuroimaging

  PRINCIPAL INVESTIGATOR

• Bastiaan R Bloem, MD, PhD

  Radboud University Medical Center, Department of Neurology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 30, 2021
• First Posted: December 27, 2021
• Study Start: December 1, 2019
• Primary Completion: November 28, 2023
• Study Completion: November 28, 2023
• Last Updated: February 21, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ANALYTIC CODE
• Time Frame: TBA.
• Access Criteria: Currently no list of criteria is available.

Locations

NL (1)