The Personalized Parkinson Project De Novo Cohort (PPP-novo)

Currently, the Movement Disorders Society (MDS)-UPDRS scale remains the gold standard to document the outcomes in clinical trials for Parkinson's disease (PD). The MDS-UPDRS is far from infallible, as it is based on subjective scoring (using a rather crude ordinal score), while execution of the tests depends on clinical experience. Not surprisingly, the scale is subject to both significant intra- and inter-rater variability that are sufficiently large to mask an underlying true difference between an effective intervention and placebo. Digital biomarkers may be able to overcome the limitations of the MDS-UPDRS, as they continuously collects real-time data, during the patient's day to day activities. In this study the investigators are interested in developing algorithms to track progression of bradykinesia, gait impairment, postural sway, tremor, physical activity, sleep quality, and autonomic dysfunction (the latter being derived from e.g. skin conductance and changes in heart rate variability).

Study Overview

• Status: Active, not recruiting
• Conditions: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinson Disease; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Neurodegenerative Diseases
• Intervention / Treatment: Device: Verily Study Watch

Detailed Description

This PPP de NOVO cohort aims to validate novel digital biomarkers for disease progression, fostering the unique research infrastructure and data collection protocol that are available. The PPP de NOVO cohort consists of patients with de novo (i.e., newly diagnosed and previously untreated) Parkinson's disease who will be followed longitudinally for two years. De novo patients create the opportunity to study disease progression without interference of pharmacological treatment. The observation of this natural process in the earliest course of the disease is highly relevant for the development disease modifying interventions, which are likely to have the biggest potential in the earliest phases of the disease, when the loss of substantia nigra cells is minimal. In particular, the investigators will deploy the PPP de NOVO cohort for the development of digital biomarkers that could serve as a surrogate or, with time, possibly as key secondary or even a primary outcome in future clinical trials of disease-modifying interventions. Digital biomarkers hold great promise in this regard, as they provide a means to objectively track patients and measure their function in their own living environment, unobtrusively, and over long periods of time. The outcomes are potentially more sensitive than currently available clinical scales, which also be included in the protocol and perhaps also more relevant as they provide an insight into daily life functioning over extended periods of time.

The primary objective is to develop novel digital biomarkers that allow for measurement of disease progression in de novo PD patients.

Our hypothesis is that digital progression biomarkers will have greater sensitivity and greater power for detecting disease progression than conventional scales.

The secondary objective is to test the feasibility of the Proof-Of-Concept (POC) study protocol that UCB (Union Chimique Belge) Pharma will use for their potentially disease modifying treatment. The PPP de NOVO study is considered instrumental in optimizing planning, data acquisition, analysis and interpretation of the digital data collected in the POC study.

The third objective of this study is to create an extensive longitudinal dataset describing the clinical and functional characteristics of a representative PD de novo cohort to allow researchers to investigate important unanswered questions in PD.

• Study Type: Observational
• Enrollment (Actual): 103

Contacts and Locations

Study Locations

• Netherlands
  • Nijmegen, Netherlands, 6500 HB
    • Radboud University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Any adult with Parkinson's disease who meets the inclusion criteria and does not meet the exclusion criteria.

Description

Inclusion Criteria:

• Subject has Parkinson's disease of ≤2 years of duration, defined as the time since the diagnosis was made by a neurologist.
• Subject is an adult, at least 18 years of age.
• Subject can read and understand Dutch.
• Subject has completed the Informed Consent, as approved by the Institutional Review Board (IRB).
• Subject is willing, competent, and able to comply with all aspects of the protocol, including follow-up schedule and bio-specimen collection.
• Subject has never been treated before with any symptomatic dopaminergic drug treatment for Parkinson's disease and is not expected to start treatment for motor symptoms of PD within 52 weeks from baseline.

Exclusion Criteria:

• Subject has co-morbidities that would hamper interpretation of parkinsonian disability, such as coincident musculoskeletal abnormalities, in the opinion of the Investigator.
• Subject is taking Mucuna Pruriens.
• For Study Watch: subject is allergic to nickel.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
PD de novo; Observational.	Device: Verily Study Watch; Participants wear the Verily Study Watch for 2 years, for longitudinal data collection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Annual change in digital biomarkers for gait	Identify (a combined set of) gait-related features extracted from wearable sensor data, that are relevant for patients and that are sensitive to disease progression in de novo PD patients. Which outcome and which Unit of Measure for gait will be selected cannot be defined on forehand, as this is part of the analytical approach, as described by Manta et al. (Digital measures of health that matter to patients. Digit Biomark 2020;4:69-77).	From baseline till two year follow-up
Annual change in digital biomarkers for tremor	Identify (a combined set of) tremor-related features extracted from wearable sensor data, that are relevant for patients and that are sensitive to disease progression in de novo PD patients. Which outcome and which Unit of Measure for tremor will be selected cannot be defined on forehand, as this is part of the analytical approach, as described by Manta et al. (Digital measures of health that matter to patients. Digit Biomark 2020;4:69-77).	From baseline till two year follow-up
Annual change in digital biomarkers for bradykinesia	Identify (a combined set of) bradykinesia-related features extracted from wearable sensor data, that are relevant for patients and that are sensitive to disease progression in de novo PD patients. Which outcome and which Unit of Measure for bradykinesia will be selected cannot be defined on forehand, as this is part of the analytical approach, as described by Manta et al. (Digital measures of health that matter to patients. Digit Biomark 2020;4:69-77).	From baseline till two year follow-up
Annual change in digital biomarkers for postural sway	Identify (a combined set of) postural sway-related features extracted from wearable sensor data, that are relevant for patients and that are sensitive to disease progression in de novo PD patients. Which outcome and which Unit of Measure for postural sway will be selected cannot be defined on forehand, as this is part of the analytical approach, as described by Manta et al. (Digital measures of health that matter to patients. Digit Biomark 2020;4:69-77).	From baseline till two year follow-up
Annual change in digital biomarkers for time active vs inactive during the day	Identify (a combined set of) features that reflect the time a person is active and inactive during the day, extracted from wearable sensor data, that are relevant for patients and that are sensitive to disease progression in de novo PD patients. Which outcome and which Unit of Measure for time active vs inactive during the day will be selected cannot be defined on forehand, as this is part of the analytical approach, as described by Manta et al. (Digital measures of health that matter to patients. Digit Biomark 2020;4:69-77).	From baseline till two year follow-up
Annual change in digital biomarkers for heart rate variability	Identify (a combined set of) features that reflect heart rate variability, extracted from wearable sensor data, that are relevant for patients and that are sensitive to disease progression in de novo PD patients. Which outcome and which Unit of Measure for heart rate variability will be selected cannot be defined on forehand, as this is part of the analytical approach, as described by Manta et al. (Digital measures of health that matter to patients. Digit Biomark 2020;4:69-77).	From baseline till two year follow-up
Annual change in digital biomarkers for skin impedance	Identify (a combined set of) features that reflect skin impedance, extracted from wearable sensor data, that are relevant for patients and that are sensitive to disease progression in de novo PD patients. Which outcome and which Unit of Measure for skin impedance will be selected cannot be defined on forehand, as this is part of the analytical approach, as described by Manta et al. (Digital measures of health that matter to patients. Digit Biomark 2020;4:69-77).	From baseline till two year follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Perceived feasibility of longitudinal follow-up and repeated assessments	Participants will be asked to complete an exit survey, which asks for their perception of the protocol burden (0-10 point scale)	From baseline till two year follow-up
Compliance to weekly structured tasks	Percentage of weeks in which the tasks were completed during the two-year follow-up (0-100%)	From baseline till two year follow-up
Compliance to wearing the smartwatch	Percentage of weartime during the two-year follow-up (0-100%)	From baseline till two year follow-up
Drop-out rate	Percentage of participants who withdraw their informed consent during the two-year follow-up (0-100%)	From baseline till two year follow-up
Change in PRO-Mobility	Participants will be asked to complete a 23-items Patient Reported Outcome (PRO) survey on mobility-related aspects, on a 0-4 scale. Total score ranges from 0-72.	From baseline till two year follow-up, every 13 weeks
Change in PGI-S Mobility	Patient Global Impression of Severity (PGI-S): participants will be asked to score their perceived severity of their mobility problems over the past 7 days on a 4-point scale (none, mild, moderate, severe)	From baseline till two year follow-up, every 13 weeks
Change in PRO-Fatigue	Participants will be asked to complete a 31-items Patient Reported Outcome (PRO) survey on fatigue-related aspects, on a 0-4 scale. Total score ranges from 0-124.	From baseline till two year follow-up, every 13 weeks
Change in PGI-S Fatigue	Patient Global Impression of Severity (PGI-S): participants will be asked to score their perceived severity level of fatigue over the past 7 days on a 4-point scale (none, mild, moderate, severe)	From baseline till two year follow-up, every 13 weeks
Change in PRO-Functional Slowness	Participants will be asked to complete a 44-items Patient Reported Outcome (PRO) survey on functional slowness-related aspects, on a 0-4 scale. Total score ranges from 0-176.	From baseline till two year follow-up, every 13 weeks
Change in PGI-S Functional Slowness	Patient Global Impression of Severity (PGI-S): participants will be asked to score their perceived severity level of functional slowness over the past 7 days on a 4-point scale (none, mild, moderate, severe)	From baseline till two year follow-up, every 13 weeks
Change in PGI-S Symptoms	Patient Global Impression of Severity (PGI-S): participants will be asked to score their perceived severity of their Parkinson's disease symptoms over the past 7 days on a 4-point scale (none, mild, moderate, severe)	From baseline till two year follow-up, every 13 weeks
Change in PGI-C Symptoms	Patient Global Impression of Change(PGI-S): participants will be asked to score their perceived change in severity of their Parkinson's disease symptoms since baseline on a 4-point scale (none, mild, moderate, severe)	From baseline till two year follow-up, every 13 weeks

Collaborators and Investigators

• Sponsor: Radboud University Medical Center
• Collaborators: UCB Pharma; Verily Life Sciences LLC
• Investigators: Principal Investigator: Bastiaan R Bloem, MD, PhD, Radboud University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): August 29, 2020
• Primary Completion (Estimated): November 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: July 22, 2021
• First Submitted That Met QC Criteria: July 22, 2021
• First Posted (Actual): August 2, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 20, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Parkinson's Disease; Biomarkers; Wearable sensors; Disease progression
• Additional Relevant MeSH Terms: Synucleinopathies; Movement Disorders; Parkinson Disease; Brain Diseases; Nervous System Diseases; Neurodegenerative Diseases; Central Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases
• Other Study ID Numbers: NL72631.091.20

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

The dataset generated in this study will become available to qualified researchers worldwide, provided research questions are approved by the Research and Data Sharing Review Committee (RDSRC). The RDSRC will protect subjects' privacy by limiting the availability of the study data and controlling access to sources of information that might potentially be used to identify the individual subjects associated with the bio-specimen analysis.

The RDSRC will assess the relevance and scientific quality of research proposals for which study data or material is requested. These responsibilities include the consideration of applications for:

• access to the resources obtained in this study, including data or biomaterials
• applications for endorsement of a scientific project using study materials;
• applications for endorsement of a clinical study using study materials.

• IPD Sharing Time Frame: Not decided yet.
• IPD Sharing Access Criteria: Currently no list of criteria is available.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No