Profiling Parkinson’s disease

Rationale: Pharmacologic treatment of Parkinson’s disease (PD) is mainly aiming to alleviate motor or neuropsychiatric symptoms and does not alter disease progression. Treatment follows a “one-size-fits-all” approach and does not consider genetic factors underlying between-patient differences in treatment response and susceptibility to adverse drug reactions (ADRs).

Primary objective: To evaluate the role of existing and novel quantitative biomarkers in understanding the heterogeneity in the Parkinson’s phenotype (i.e. rate of progression, cognitive and neuropsychiatric impairment and motor dysfunction) and predicting treatment response as well as the occurrence of ADRs over a three-year period.

Secondary Objective: To develop a biobank containing comprehensive and uniformly acquired longitudinal clinical data and biological samples for identification and validation of biomarker panels and data-driven approaches to unravel heterogeneity in the Parkinson’s phenotype (i.e. rate of progression, cognitive and neuropsychiatric impairment and motor dysfunction), treatment response and occurrence of ADRs.

Study design: longitudinal cohort study

Study population: 1250 patients diagnosed with PD with a disease duration of less than 10 years (since diagnosis), as well as 265 healthy, age and gender-matched controls.

Main study parameters/endpoints: main study parameters are biomarker concentrations (i.e. blood & feces), skin alpha-synuclein (α-syn) aggregation, treatment response, ADR occurrence and cognitive and neuropsychiatric scores.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Participants are invited to come to one of the study sites in Leiden (LUMC), Amsterdam (Amsterdam UMC, location AMC or VUmc), Rotterdam (Erasmus), Utrecht/Woerden (Antonius) or Amersfoort (Meander) for 2 hours of data collection (annually at T0, T1, T2 and T3). Additionally, these visits come with a 35 min (at T1, T2, T3) to 50 min (at T0) phone interview, 145 min (T1, T2, T3) to 160 min (T0) online questionnaires and one week of wearable sensor data collection at home (T0, T1, T2 and T3). The semi-annual follow-ups (T0.5, T1.5, T2.5) consist of a phone interview of 10 min, 115 min of online questionnaires and 1 week of wearable sensor data collection. Controls will be assessed twice (T0 and T2). All clinical study assessments are not part of standard clinical practice but are generally well tolerated. Only at Amsterdam UMC, location VUmc, a part of the clinical assessment and questionnaires at baseline are performed in standard clinical practice in de novo Parkinson patients (i.e. day screening). Assessments and questionnaires that overlap with ProPark (except for the MDS-UPDRS, SAPS-PD, Hoehn & Yahr and orthostatic hypotension) will not be administered twice. With approval from the participant, the results of the overlapping assessments and questionnaires from the day screening will be used for ProPark. Blood, feces (annually) and skin biopsies (only at T0 and T2 and only in 400 patients and 100 controls) will be collected. Blood sampling and skin biopsies come with a small discomfort. Risks associated with a venous blood puncture and skin biopsies include a local hematoma and, rarely, an infection. These risks will be minimized by the applied puncture procedures carried out by experienced physicians/nurses. Wrist and lower back sensors will be worn daily for up to 24 hours, twice a year for a one week period by patients (adding up to a total of 7 weeks throughout the study) and twice for a one week period by controls (adding up to a total of 2 weeks throughout the study).These small electronic devices are easily applied and pose no significant safety issues.

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Patients will be clinically assessed at baseline and during annual follow-ups in the hospital and at home (T0, T1, T2, T3) and during semi-annual follow-ups at home (T0.5, T1.5, T2.5).