Study protocol of the DUtch PARkinson Cohort (DUPARC): a prospective, observational study of de novo Parkinson's disease patients for the identification and validation of biomarkers for Parkinson's disease subtypes, progression and pathophysiology

Jeffrey M Boertien, Sygrid van der Zee, Asterios Chrysou, Marleen J J Gerritsen, Nomdo M Jansonius, Jacoba M Spikman, Teus van Laar, PPNN Study Group, N A Verwey, B Van Harten, A T Portman, M J H Langedijk, P G Oomes, B J A M Jansen, T Van Wieren, S J A Van den Bogaard, W Van Steenbergen, R Duyff, J P Van Amerongen, P S S Fransen, S K L Polman, R T Zwartbol, M E Van Kesteren, J P Braakhekke, J Trip, L Koops, C J De Langen, G De Jong, J E S Hartono, H Ybema, A L Bartels, F E Reesink, A G Postma, G J H Vonk, J M T H Oen, M J Brinkman, T Mondria, R S Holscher, A A E Van der Meulen, A W F Rutgers, W A Boekestein, L K Teune, P J L Orsel, J E Hoogendijk, T Van Laar, Jeffrey M Boertien, Sygrid van der Zee, Asterios Chrysou, Marleen J J Gerritsen, Nomdo M Jansonius, Jacoba M Spikman, Teus van Laar, PPNN Study Group, N A Verwey, B Van Harten, A T Portman, M J H Langedijk, P G Oomes, B J A M Jansen, T Van Wieren, S J A Van den Bogaard, W Van Steenbergen, R Duyff, J P Van Amerongen, P S S Fransen, S K L Polman, R T Zwartbol, M E Van Kesteren, J P Braakhekke, J Trip, L Koops, C J De Langen, G De Jong, J E S Hartono, H Ybema, A L Bartels, F E Reesink, A G Postma, G J H Vonk, J M T H Oen, M J Brinkman, T Mondria, R S Holscher, A A E Van der Meulen, A W F Rutgers, W A Boekestein, L K Teune, P J L Orsel, J E Hoogendijk, T Van Laar

Abstract

Background: Parkinson's Disease (PD) is a heterogeneous, progressive neurodegenerative disorder which is characterized by a variety of motor and non-motor symptoms. To date, no disease modifying treatment for PD exists. Here, the study protocol of the Dutch Parkinson Cohort (DUPARC) is described. DUPARC is a longitudinal cohort study aimed at deeply phenotyping de novo PD patients who are treatment-naïve at baseline, to discover and validate biomarkers for PD progression, subtypes and pathophysiology.

Methods/design: DUPARC is a prospective cohort study in which 150 de novo PD subjects will be recruited through a collaborative network of PD treating neurologists in the northern part of the Netherlands (Parkinson Platform Northern Netherlands, PPNN). Participants will receive follow-up assessments after 1 year and 3 years, with the intention of an extended follow-up with 3 year intervals. Subjects are extensively characterized to primarily assess objectives within three major domains of PD: cognition, gastrointestinal function and vision. This includes brain magnetic resonance imaging (MRI); brain cholinergic PET-imaging with fluoroethoxybenzovesamicol (FEOBV-PET); brain dopaminergic PET-imaging with fluorodopa (FDOPA-PET); detailed neuropsychological assessments, covering all cognitive domains; gut microbiome composition; intestinal wall permeability; optical coherence tomography (OCT); genotyping; motor and non-motor symptoms; overall clinical status and lifestyle factors, including a dietary assessment; storage of blood and feces for additional analyses of inflammation and metabolic parameters. Since the start of the inclusion, at the end of 2017, over 100 PD subjects with a confirmed dopaminergic deficit on FDOPA-PET have been included.

Discussion: DUPARC is the first study to combine data within, but not limited to, the non-motor domains of cognition, gastrointestinal function and vision in PD subjects over time. As a de novo PD cohort, with treatment naïve subjects at baseline, DUPARC provides a unique opportunity for biomarker discovery and validation without the possible confounding influences of dopaminergic medication.

Trial registration: NCT04180865; registered retrospectively, November 28th 2019.

Keywords: Biomarkers; Cognition; Gastrointestinal microbiome; Longitudinal studies; Microbiota; Neurodegenerative diseases; Neuropsychology; Observational study; Ophthalmology; Parkinson disease.

Conflict of interest statement

TvL has received research support from the Weston Brain Institute, speaker fees from Britannia, AbbVie and Medtronic, and is on the advisory boards of LTI and Neuroderm.

Figures

Fig. 1
Fig. 1
Baseline recruitment and assessments from Q4 2017 to Q3 2020 of treatment-naïve de novo PD subjects through the collaborative network of PD treating neurologists Parkinson Platform Northern Netherlands (PPNN). 1. Study procedures start at home with 1a. the collection of a saliva sample for genetic screening; 1b. Assessments of gastrointestinal function and stool sample collection; 1c. questionnaire assessments. 2. Participants visit the University Medical Center Groningen (UMCG) on 2 days for 2a. a complete cognitive assessment; 2b. imaging; 2c. ophthalmological assessments; 2d. clinical assessments. * In a subset of participants, intestinal wall permeability will also be assessed using blood samples and a urinary excretion test. ** Hyposmia is also assessed using the Sniffin’ sticks. Source clipart: clipart-library.com

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