Clinical trial NCT04985539: The Personalized Parkinson Project De Novo Cohort
Official title: The Personalized Parkinson Project De Novo Cohort
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Parkinson Disease
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Keywords: Parkinson's Disease
Biomarkers
Wearable sensors
Disease progression
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
Collaborators: name: UCB Pharma
name: Verily Life Sciences LLC
First posted: 2021-08-02
Enrollment: 103
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

Brief summary: 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).

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Annual change in digital biomarkers for gait
timeFrame: From baseline till two year follow-up
measure: Annual change in digital biomarkers for tremor
timeFrame: From baseline till two year follow-up
measure: Annual change in digital biomarkers for bradykinesia
timeFrame: From baseline till two year follow-up
measure: Annual change in digital biomarkers for postural sway
timeFrame: From baseline till two year follow-up
measure: Annual change in digital biomarkers for time active vs inactive during the day
timeFrame: From baseline till two year follow-up
measure: Annual change in digital biomarkers for heart rate variability
timeFrame: From baseline till two year follow-up
measure: Annual change in digital biomarkers for skin impedance
timeFrame: From baseline till two year follow-up
Secondary outcomes:
measure: Perceived feasibility of longitudinal follow-up and repeated assessments
timeFrame: From baseline till two year follow-up
measure: Compliance to weekly structured tasks
timeFrame: From baseline till two year follow-up
measure: Compliance to wearing the smartwatch
timeFrame: From baseline till two year follow-up
measure: Drop-out rate
timeFrame: From baseline till two year follow-up
measure: Change in PRO-Mobility
timeFrame: From baseline till two year follow-up, every 13 weeks
measure: Change in PGI-S Mobility
timeFrame: From baseline till two year follow-up, every 13 weeks
measure: Change in PRO-Fatigue
timeFrame: From baseline till two year follow-up, every 13 weeks
measure: Change in PGI-S Fatigue
timeFrame: From baseline till two year follow-up, every 13 weeks
measure: Change in PRO-Functional Slowness
timeFrame: From baseline till two year follow-up, every 13 weeks
measure: Change in PGI-S Functional Slowness
timeFrame: From baseline till two year follow-up, every 13 weeks
measure: Change in PGI-S Symptoms
timeFrame: From baseline till two year follow-up, every 13 weeks
measure: Change in PGI-C Symptoms
timeFrame: From baseline till two year follow-up, every 13 weeks
Other outcomes:
Locations:
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Center
Study officials:
affiliation: Radboud University Medical Center
name: Bastiaan R Bloem, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: