Telemedicine and smartphone-based remote sensor assessments represent particularly promising opportunities to streamline study conduct, reduce participant burden, and allow for the collection of data beyond the usual episodic, in-clinic assessments. Demonstrating the utility of these relatively inexpensive accessible platforms for the measurement of PD progression would also establish the infrastructure for long-term follow up of participants after completion of interventional studies.
STEADY-PD3 (a.k.a. STEADY-PD III) and SURE-PD3 were both designed as phase 3 trials of potential disease-modifying interventions in PD. In both studies, early, largely untreated PD participants were randomized in 1:1 allocation to active therapy versus placebo with longitudinal follow up for three and two years, respectively. Both studies include collection of blood plasma and DNA samples, which along with rigorously collected clinical data will become part of the Parkinson's Disease Biomarker Program (PDBP), providing valuable resources for biomarker development. Long-term observation of participants from these two trials, together comprising ~600 early PD subjects, is invaluable not only in characterizing any persistent or delayed benefits of either randomized treatment but also in the development of tele-health outcomes to facilitate future interventional trials in PD and of neurotherapeutics more broadly.
Challenges of traditional long-term follow up of large cohorts are the high cost of in-clinic assessment, the high dropout rates and the need to maintain multi-site infrastructure. The objective of this study is to leverage modern technology to develop, pilot and implement a 100% virtual model for long-term follow up utilizing telemedicine and smartphone platforms for quantitative monitoring of clinician- and patient-reported outcomes. This cohort may also serve to test feasibility of new technology platforms as they become available.
Disease modification is the primary unmet need in Parkinson’s disease (PD) therapeutics. Currently clinical trials of promising candidate neuroprotectants are limited by the inefficiency and imprecision of repeated in person clinical assessments required of people with Parkinson’s who volunteer to participate in these studies. Emerging telemedicine and smartphone-based remote sensor assessments provide opportunities to help overcome these obstacles and improve prospects for the success of future trials. Demonstrating the utility of these relatively inexpensive accessible tele-health platforms for the measurement of PD progression would also establish infrastructure for long-term follow up of participants after completion of interventional studies. STEADY-PD3 and SURE-PD3 are active NINDS-funded phase 3 trials of potential disease-modifying interventions in PD. Both studies, comprising ~600 early PD subjects, include biomarker sub-studies collecting DNA and serial plasma samples and, in a subset, serial dopamine transporter (DAT) neuroimaging data that will become part of the Parkinson’s Disease Biomarker Program (PDBP). The objective of this proposal is to leverage modern technology to develop, pilot and implement a 100% virtual model for long-term follow up utilizing telemedicine and smartphone platforms for quantitative monitoring of clinician- and patient-reported outcomes. Specific Aim (SA) 1 is to establish infrastructure for longitudinal remote follow up of phase 3 trial cohorts; a) transitioning from site-based to a centralized coordination center to manage all subject activity, b) conducting an annual telemedicine research visit (tele-visit) program, and c) implementing a smartphone data collection platform tailored to a clinical trial cohort. SA2 is to compare smartphone (patient-driven) vs tele-visit (clinician-driven) outcomes by a) correlating these platforms’ component and composite features, and their changes over years, and b) comparing their abilities to i) measure PD progression; ii) distinguish rapid vs slow progressors based on baseline motor scale scores, DAT deficit or serum urate levels; and iii) demonstrate persistence of any effects of isradipine or inosine in their respective trials. SA3 is to explore novel smartphone-based real-life mobility biomarkers of PD disability and its progression that are normally inaccessible with traditional office measures. The ability of passively collected smartphone data, on ambulation and location, to enable assessments of physical activity and socialization that meaningfully integrate motor and non-motor functions will be investigated. This project leverages the major phase 3 trial investments of NIH and study subjects by extending their follow up to establish the utility of tele-health metrics for tracking PD progression in clinical cohorts. Its results are expected to accelerate effective testing of a greater number of promising candidates for disease modification. The results will have an immediate impact on the rational selection of smartphone versus tele-visit monitoring in designing the next generation of PD trials, and may help identify and substantiate novel digital as well as molecular biomarkers of PD.
The overarching goal of the AT-HOME PD study is to improve the ability of future clinical trials to demonstrate disease-modifying treatment benefits in people with Parkinson’s by comparing and validating tele-health assessments of their clinical progression. Specifically, the study seeks:
- to enroll people with Parkinson’s who have participated in STEADY-PD3 and SURE-PD3, two clinical trials that carefully characterized their early PD progression with traditional office visit assessments. The study seeks to enroll 70% of the STEADY-PD3 and SURE-PD3 cohorts in at least the tele-visit portion of the study and 80% of the enrollees in the smartphone portion of the study.
- to establish a clinical research infrastructure for long-term remote follow up of these participants in their usual (e.g., home) environment using a centrally managed platforms for annual tele-visits and at least quarterly smartphone sessions that monitor progressive features of PD.
- to compare smartphone (patient-driven) vs tele-visit (clinician-driven) outcomes over years to characterize their relative utility for measuring progression and distinguishing subtypes of the disease.
- to explore novel smartphone-based measures of mobility that reflect socialization as well as physical movement, and the loss of this mobility as PD progresses.