Assessing Tele-Health Outcomes in Multiyear Extensions of PD Trials

Study Overview
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Brief Summary
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An observational study to characterize and compare long-term clinical outcomes data collected remotely through periodic tele-visits, interactive smartphone app sessions, and web-based surveys in individuals with Parkinson's Disease (PD) who have completed the interventional phases of the STEADY-PD3 and SURE-PD3 clinical trials.

Detailed Description
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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, de novo 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 DNA and plasma 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 (PROs). This cohort may also serve to test feasibility of new technology platforms as they become available.

Official Title
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Tele-health Outcomes as Digital Biomarkers of Parkinson's Disease Progression During Extended Follow up of STEADY-PD3 and SURE-PD3 Trial Participants

Conditions
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Parkinson Disease

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Enrollment in STEADY-PD3 or SURE-PD3 studies Prior consent to be contacted by the University of Rochester (UR) or if a participant from STEADY-PD III or SURE-PD3 studies directly contacts UR to request information about study participation Internet-enabled device that will support participation in tele-visits Have created or willing to create a Global Unique Identifier (GUID) Willing and able to provide informed consent English fluency For participants opting to participate in the smartphone component, possession of a suitable smartphone (iPhone or Android) with adequate data plan and cellular network access/signal or wifi access Exclusion Criteria: 1. Inability to carry out study activities as determined by study staff
Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| former phase 3 PD trial participants<br>The AT-HOME PD cohort enrolled upon completion of STEADY-PD3 or during completion of SURE-PD3; enrolling 2 to 6 years after diagnosis, and on standard dopaminergic therapy for 0 to 3 years. Former STEADY-PD3 participants had been randomized (1:1) to 3 years of isradipine or placebo treatment; SURE-PD3 participants had been randomized (1:1) to 2 years of inosine or placebo treatment. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Tele-visit Modified MDS-UPDRS Parts 1-3 (Total Score) | Participants will be asked to complete (from home or other preferred environment) an hour-long Tele-visit that includes the Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS), comprising MDS-UPDRS part 1a and (modified) part 3, as well as completion or confirmation of patient-reported component parts 1b and 2. The MDS-UPDRS is assessed on a 5-point Likert scale ranging from 0 to 4 where higher scores imply worse features. Parts I-III contain 59 total questions (13 in Part I, 13 in Part II, and 33 in Part III). Total scores are calculated as simple sums of component items with mean imputation by Part if no more than 1, 2, or 7 items are missing for Parts I through III, respectively. Total scores may range from 0 to 236, with 0 meaning no symptoms and 236 meaning worse symptoms. | Two years (0, 12, and 24 months) | 
| Change in Tele-visit MDS-UPDRS Part 2 (Score) | The Movement Disorders Society Unified PD Rating Scale (MDS-UPDRS) Part II score comprises patient-reported responses to 13 questions on motor experiences of daily living. The response to each question is assessed on a 5-point Likert scale ranging from 0 to 4 where higher scores imply worse symptoms. Part II scores may range from a minimum of 0 to a maximum of 52, with higher values meaning worse symptoms. | Two years (0, 12, and 24 months) | 
| Change in Smartphone Tapping (Score) | The Smartphone Tapping Score is derived from a 30-second finger tapping task performed separately for each hand. The score ranges from 0 to 1 and higher scores are worse. | Two years (0, 3, 6, 9, 12 , 15, 18, 21, and 24 months) | 
| Change in Fox Insight MDS-UPDRS Part 2 (Score) | The Fox Insight MDS-UPDRS (Movement Disorders Society Unified PD Rating Scale) Part II score comprises patient-reported responses to 13 questions on motor experiences of daily living. Participants report their responses online through the Fox Insight web-based platform. The response to each question is assessed on a 5-point Likert scale ranging from 0 to 4 where higher scores imply worse symptoms. Part II scores may range from a minimum of 0 to a maximum of 52, with higher values meaning worse symptoms. | Two years (0, 6, 12, 18, and 24 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Tele-visit MDS-UPDRS Part 1a (Score) | Participants will be asked to complete (from home or other preferred environment) an hour-long Tele-visit that includes the Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS), comprising MDS-UPDRS part 1a (i.e., the first six questions of part 1). The MDS-UPDRS is assessed on a 5-point Likert scale ranging from 0 to 4 where higher scores imply worse features. Part 1a scores may range from a minimum of 0 to a maximum of 24, with higher values meaning worse disability. | Two years (0, 12, and 24 months) | 
| Change in Tele-visit MDS-UPDRS Part 1b (Score) | The Movement Disorders Society Unified PD Rating Scale (MDS-UPDRS) Part Ib is the patient-reported portion of Part I, and assesses non-motor experiences of daily living. The MDS-UPDRS is assessed on a 5-point Likert scale ranging from 0 to 4 where higher scores imply worse symptoms. Part Ib contains 7 questions, and its scores may range from a minimum of 0 to a maximum of 28, with higher values meaning worse symptoms. | Two years (0, 12, and 24 months) | 
| Change in Tele-visit Modified MDS-UPDRS Part 3 (Score) | Participants will be asked to complete (from home or other preferred environment) an hour-long Tele-visit that includes the Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS), comprising MDS-UPDRS (modified) part 3. This measure omits 5 questions related to rigidity and 1 question related to postural instability, with a range from 0 to 108. The MDS-UPDRS is assessed on a 5-point Likert scale ranging from 0 to 4 where higher scores imply worse features. | Two years (0, 12, and 24 months) | 
| Change in Tele-visit Montreal Cognitive Assessment (MoCA; Score) | The Montreal Cognitive Assessment (MoCA) assesses attention and concentration, executive functions, memory, language, visuoconstructional skills, conceptual thinking, calculations, and orientation. Points are awarded for the correct completion of MoCA tasks. Scores for each task are summed for a total score (range 0-30). Higher scores indicate greater cognitive capacity. | Two years (0, 12, and 24 months) | 
| Change in Tele-visit Schwab and England (S&E; Score) | The Schwab and England scale is a Site Investigator and subject assessment of the subject's level of independence. The subject will be scored on a percentage scale reflecting his/her ability to perform acts of daily living. Printed scores with associated descriptors range from 0% to 100% in increments of 5%, with higher percentages associated with more independence. A score of 0% implies vegetative functions such as swallowing, bladder and bowel functions are not functioning; bedridden. A score of 100% implies subject has full ability and is completely independent; essentially normal. | Two years (0, 12, and 24 months) | 
| Change in Tele-visit Clinician Global Impression - Severity (CGIS; Score) | The Clinician Global Impression (CGI) is an observer-rated scale that measures illness severity (CGIS). The CGIS is rated on a 7-point scale, with the severity of illness scale using a range of responses from 1 (normal) through 7 (amongst the most severely ill patients). | Two years (0, 12, and 24 months) | 
| Change in Fox Insight Parkinson's Disease Questionnaire - 8 Item Version (PDQ-8; Score) | The Fox Insight PDQ-8 (Parkinson's Disease Questionnaire, short-form 8 item version) is a self-administered questionnaire used to measure quality of life in persons with Parkinson's disease. The response to each question is assessed on a 5-point Likert scale ranging from 0 to 4 where higher scores imply worse symptoms. Scores range from a minimum of 0 to a maximum of 32, with a higher score indicating a poorer quality of life. | Two years (0, 3, 6, 9, 12, 15, 18, 21, and 24 months) | 
| Change in Fox Insight EuroQol Five Dimensions Questionnaire (EQ-5D; Score) | The Fox Insight EQ-5D (European Quality of life survey) is a standardized measure of health-related quality of life assessing five dimensions of health. It comprises five corresponding questions on mobility, self-care, pain, usual activities, and psychological status with three possible answers for each item (1=no problem, 2=moderate problem, 3=severe problem). A derived summary index score is higher with better health-related quality of life. A maximum of 1 corresponds to the best quality of life, whereas a score of 0 is intended to approximate a state equivalent to death, with values less than 1 corresponding to a state worse than death. | Two years (0, 6, 12, 18, and 24 months) | 
| Change in Fox Insight Non-motor Symptoms Questionnaire (NMS-QUEST; Score) | The Non-motor Symptoms Questionnaire (NMS-QUEST) is a 30-question self-reported assessment. Each question is of a yes/no format with a score of 1 given to each yes answer, with total scores ranging from 0-30, with higher scores indicating a greater number of non-motor symptoms. Participants completed the assessment online in Fox Insight. | Two years (0, 3, 6, 9, 12, 15, 18, 21, and 24 months) | 
| Change in Fox Insight REM (Rapid Eye Movement) Behavior Disorder (RBD; Score) | The Fox Insight Rapid Eye Movement Behavior Disorder (RBD) score is a patient-reported binary (no or yes) response to a single question of whether they act out their dreams while asleep. Participants report their response online through the Fox Insight web-based platform. The score value is dichotomous (or missing) and ranges from 0 (no symptom) to 1 (yes response). | Two years (0, 3, 6, 9, 12, 15, 18, 21, and 24 months) | 
| Change in Fox Insight Parkinson's Daily Activities Questionnaire -15 (PDAQ-15; Score) | The Parkinson's Daily Activities Questionnaire -15 (PDAQ-15) is a 15-item measure of activities of daily living (ADL) that are impacted by cognitive impairment in participants with Parkinson's disease. The PDAQ-15 is derived from the original 50-item scale and is completed by the participant in Fox Insight. Scores range from 0 to 60, with higher scores indicating better function. | Two years (0, 3, 9, 15, and 21 months) | 
| Change in Fox Insight Geriatric Depression Scale (GDS; Score) | The Geriatric Depression Scale (GDS) is a measure of depression completed by the participant online in Fox Insight. The scale has 30 yes/no questions, with each question having a maximum score of 1 and a total possible score ranging from 0 to 30. The higher the score, the greater the depression. | Two years (0, 12, and 24 months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SURE-PD3, STEADY-PD III, Parkinson disease, PD, Parkinson Study Group (PSG), Telemedicine, Smartphone, Disease progression, Televisits, Patient-reported outcomes