Trial Outcomes & Findings for Real-PD Trial: Development of Clinical Prognostic Models for Parkinson's Disease (NCT NCT02474329)

Last Updated: 2021-12-06

Results Overview

The MDS-UPDRS is a revision of the Unified Parkinson's Disease Rating Scale (UPDRS). It was developed to evaluate various aspects of Parkinson's disease including non-motor and motor experiences of daily living, as well as motor complications. The MDS-UPDRS characterizes the extent and burden of disease across various populations. Here, we used data from one-point assessment (baseline). The total score used here was calculated by a sum of all scores from the 4 sub-scales (i.e. part I, up to part IV) composing the MDS-UPDRS. Total score ranges from 0 to 272. A higher score indicates higher disease severity and burden, being thus a worse outcome.

Recruitment status

COMPLETED

Target enrollment

304 participants

Primary outcome timeframe

Baseline

Results posted on

2021-12-06

Participant Flow

After changing the inclusion process for one cohort only, a total of 347 eligible PD patients were invited to participate. Among those invited, 43 refused to participate. The main refusal reasons were "Study protocol seems too burdensome" (44%, n = 19), followed by "Personal circumstances" (33%, n = 14). A total of 304 patients (enrolment rate = 88%) were enrolled.

Participant milestones

Participant milestones
Measure	Cohort 1 Dutch Parkinson's patients who fulfill the eligibility criteria. Interventions/Exposures to be administered: 1. PPMI (Parkinson's Progression Markers Initiative) protocol Trained physiotherapists will perform once a standardized clinical assessment to every included patient. This assessment will last for 60 minutes, and it will be done once. 2. Fox Insight self-monitoring android app and falls detector Patients will wear a smartwatch and a pendant movement sensor during day and night, for a period of 13 weeks. Additionally, a self-monitoring App on a Smartphone is used, where the patient reports when (s)he takes any PD medication. An additional, optional button allows the patient to report general feeling.
Overall Study STARTED	304
Overall Study COMPLETED	291
Overall Study NOT COMPLETED	13

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort 1 Dutch Parkinson's patients who fulfill the eligibility criteria. Interventions/Exposures to be administered: 1. PPMI (Parkinson's Progression Markers Initiative) protocol Trained physiotherapists will perform once a standardized clinical assessment to every included patient. This assessment will last for 60 minutes, and it will be done once. 2. Fox Insight self-monitoring android app and falls detector Patients will wear a smartwatch and a pendant movement sensor during day and night, for a period of 13 weeks. Additionally, a self-monitoring App on a Smartphone is used, where the patient reports when (s)he takes any PD medication. An additional, optional button allows the patient to report general feeling.
Overall Study Withdraw or did not contribute data.	13

Baseline Characteristics

Age at disease onset was first included as an outcome. During data-collection, we have chosen not to collect it because other measures (such as MDS-UPDRS) better reflects the impact, burden and severity of the disease.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1 n=291 Participants Dutch Parkinson's patients who fulfill the eligibility criteria. Interventions/Exposures to be administered: 1. PPMI (Parkinson's Progression Markers Initiative) protocol Trained physiotherapists will perform once a standardized clinical assessment to every included patient. This assessment will last for 60 minutes, and it will be done once. 2. Fox Insight self-monitoring android app and falls detector Patients will wear a smartwatch and a pendant movement sensor during day and night, for a period of 13 weeks. Additionally, a self-monitoring App on a Smartphone is used, where the patient reports when (s)he takes any PD medication. An additional, optional button allows the patient to report general feeling.
Age, Categorical <=18 years	0 Participants n=291 Participants
Age, Categorical Between 18 and 65 years	30 Participants n=291 Participants
Age, Categorical >=65 years	261 Participants n=291 Participants
Sex: Female, Male Female	123 Participants n=291 Participants
Sex: Female, Male Male	168 Participants n=291 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=291 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	0 Participants n=291 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	291 Participants n=291 Participants
Disease severity Stage 0 or 1	73 Participants n=291 Participants
Disease severity Stage 2	127 Participants n=291 Participants
Disease severity Stage 3	34 Participants n=291 Participants
Disease severity Stage 4 or 5	6 Participants n=291 Participants
Disease severity Missing	51 Participants n=291 Participants
Depression No	238 Participants n=291 Participants
Depression Yes	53 Participants n=291 Participants
Cognitive impairment No	124 Participants n=291 Participants
Cognitive impairment Yes	167 Participants n=291 Participants
Independency level Equal or small to 70	36 participants n=291 Participants
Independency level 71-80	51 participants n=291 Participants
Independency level 81-90	110 participants n=291 Participants
Independency level Equal or higher to 91	41 participants n=291 Participants
MDS-UPDRS	52.5 units on a scale n=291 Participants
Level of education Low	51 Participants n=291 Participants
Level of education Middel	103 Participants n=291 Participants
Level of education High	101 Participants n=291 Participants
Level of education Missing	36 Participants n=291 Participants

PRIMARY outcome

Timeframe: Baseline

Population: We have analysed data from all participants who completed the study.

Outcome measures

Outcome measures
Measure	Cohort 1 n=291 Participants Dutch Parkinson's patients resident in the region of Noord-Holland whose fulfill the eligibility criteria. Interventions/Exposures to be administered: 1. PPMI (Parkinson's Progression Markers Initiative) protocol Trained physiotherapists will perform once a standardized clinical assessment to every included patient. This assessment will last for 60 minutes, and it will be done once. 2. Fox Insight self-monitoring android app and falls detector Patients will wear a smartwatch and a pendant movement sensor during day and night, for a period of 13 weeks. Additionally, a self-monitoring App on a Smartphone is used, where the patient reports when (s)he takes any PD medication. An additional, optional button allows the patient to report general feeling. Clinical assessment: During the 13 week follow-up, trained physiotherapists will perform a standardized clinical assessment, based on the PPMI protocol (www.ppmi-info.ors) for every included patient. This assessment will last for 60 minutes, and it will be done once. Fox Insight self-monitoring android app and falls detector: Patients will be asked to wear a smartwatch and a pendant movement sensor, both with triaxial accelerometers, during day and night, for a period of 13 weeks. Additionally, a self-monitoring App on a Smartphone is used, where the patient reports when (s)he takes any PD medication. An additional, optional button allows the patient to report general feeling.
Parkinson's Disease Symptoms	52.5 units on a scale Interval 35.0 to 69.0

PRIMARY outcome

Timeframe: Baseline

Population: We have analyzed all participants who completed the study.

The scores obtained with the Geriatric Depression Scale were analysed in order to create a percentage of probably depressed participants. The total score goes from 0 to 15. A score higher than 6 indicates higher probability of suffer from a depression.

Outcome measures

Outcome measures
Measure	Cohort 1 n=291 Participants Dutch Parkinson's patients resident in the region of Noord-Holland whose fulfill the eligibility criteria. Interventions/Exposures to be administered: 1. PPMI (Parkinson's Progression Markers Initiative) protocol Trained physiotherapists will perform once a standardized clinical assessment to every included patient. This assessment will last for 60 minutes, and it will be done once. 2. Fox Insight self-monitoring android app and falls detector Patients will wear a smartwatch and a pendant movement sensor during day and night, for a period of 13 weeks. Additionally, a self-monitoring App on a Smartphone is used, where the patient reports when (s)he takes any PD medication. An additional, optional button allows the patient to report general feeling. Clinical assessment: During the 13 week follow-up, trained physiotherapists will perform a standardized clinical assessment, based on the PPMI protocol (www.ppmi-info.ors) for every included patient. This assessment will last for 60 minutes, and it will be done once. Fox Insight self-monitoring android app and falls detector: Patients will be asked to wear a smartwatch and a pendant movement sensor, both with triaxial accelerometers, during day and night, for a period of 13 weeks. Additionally, a self-monitoring App on a Smartphone is used, where the patient reports when (s)he takes any PD medication. An additional, optional button allows the patient to report general feeling.
Depression Scores as a Measure of Depression Rates No	238 Participants
Depression Scores as a Measure of Depression Rates Yes	53 Participants

PRIMARY outcome

Timeframe: Baseline

Population: We analyzed all participants who completed the study.

Total sum score obtained with the Montreal Cognitive Assessment. We analyzed the full score to investigate percentage of participants with a possible cognitive impairment. The Montreal Cognitive sum scores ranges from 0 to 30, in which a score lower or equal to 26 is considered as possible cognitive decline.

Outcome measures

Outcome measures
Measure	Cohort 1 n=291 Participants Dutch Parkinson's patients resident in the region of Noord-Holland whose fulfill the eligibility criteria. Interventions/Exposures to be administered: 1. PPMI (Parkinson's Progression Markers Initiative) protocol Trained physiotherapists will perform once a standardized clinical assessment to every included patient. This assessment will last for 60 minutes, and it will be done once. 2. Fox Insight self-monitoring android app and falls detector Patients will wear a smartwatch and a pendant movement sensor during day and night, for a period of 13 weeks. Additionally, a self-monitoring App on a Smartphone is used, where the patient reports when (s)he takes any PD medication. An additional, optional button allows the patient to report general feeling. Clinical assessment: During the 13 week follow-up, trained physiotherapists will perform a standardized clinical assessment, based on the PPMI protocol (www.ppmi-info.ors) for every included patient. This assessment will last for 60 minutes, and it will be done once. Fox Insight self-monitoring android app and falls detector: Patients will be asked to wear a smartwatch and a pendant movement sensor, both with triaxial accelerometers, during day and night, for a period of 13 weeks. Additionally, a self-monitoring App on a Smartphone is used, where the patient reports when (s)he takes any PD medication. An additional, optional button allows the patient to report general feeling.
Cognitive Impairment. No cognitive decline	125 Participants
Cognitive Impairment. Possible cognitive decline	166 Participants

PRIMARY outcome

Timeframe: Baseline

Population: We analyzed all participants who completed the study.

The total sum score obtained with the Schwab and England activities of daily living scale were analyzed to describe the functional level of the sample. The total sum scores varies from 0 to 100, in which lower scores are associated with more dependency of others to perform daily life activities.

Outcome measures

Outcome measures
Measure	Cohort 1 n=291 Participants Dutch Parkinson's patients resident in the region of Noord-Holland whose fulfill the eligibility criteria. Interventions/Exposures to be administered: 1. PPMI (Parkinson's Progression Markers Initiative) protocol Trained physiotherapists will perform once a standardized clinical assessment to every included patient. This assessment will last for 60 minutes, and it will be done once. 2. Fox Insight self-monitoring android app and falls detector Patients will wear a smartwatch and a pendant movement sensor during day and night, for a period of 13 weeks. Additionally, a self-monitoring App on a Smartphone is used, where the patient reports when (s)he takes any PD medication. An additional, optional button allows the patient to report general feeling. Clinical assessment: During the 13 week follow-up, trained physiotherapists will perform a standardized clinical assessment, based on the PPMI protocol (www.ppmi-info.ors) for every included patient. This assessment will last for 60 minutes, and it will be done once. Fox Insight self-monitoring android app and falls detector: Patients will be asked to wear a smartwatch and a pendant movement sensor, both with triaxial accelerometers, during day and night, for a period of 13 weeks. Additionally, a self-monitoring App on a Smartphone is used, where the patient reports when (s)he takes any PD medication. An additional, optional button allows the patient to report general feeling.
Independency Level Lower or equal to 70	36 Participants
Independency Level Higher than 70 and lower than 81	51 Participants
Independency Level Higher than 80 and lower than 91	109 Participants
Independency Level higher than 90	41 Participants
Independency Level Missing	54 Participants

SECONDARY outcome

Timeframe: Patients will be automatically assessed during the follow-up time (up to 13 weeks after the enrollment date), 24 hours a day, 7 days a week.

Population: We invited 43 study participants to wear the fall detector, of whom 13 consented to wear it. Unfortunately the quality of the collected data did not allow for automated falls detection. Therefore we couldn't determine this outcome measure.

The fall event is recognized by the falls detector. Every time that the patient falls, the algorithm embedded at the falls detector recognize as a fall and record the fall event. At the end of the follow-up time, a sum of the falls event for each patient will be done.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Patients will be assessed during the follow-up time (up to 13 weeks after the enrollment date). It is expected that the assessment (self-report) will be performed as many times as the patient wants to report how they feel or at least once a day.

Population: Though the smartphone application had to option to report "mood", participants hardly used this feature. Therefore there were no data collection that were suitable for analysis.

The number of mood reports will be collected through the smartphone application. A four point scale (very good, good, poor and fair) will be available, and by pressing the button which correspond to how the patient feels at that moment the report can be performed. At the end of the follow-up time a sum of all the reports will be done in order to measure the number of mood reports over the follow-up time.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline

Population: 96% (n = 280) of data-contributors reported their medication through the app.

The number of medication intake annotations made by the patients will be collected through the smartphone application. Every time that the patient take medication they must press the button reporting that they took the medication. At the end of the follow-up time a sum of all the reports will be done in order to measure the number of medication intake over the follow-up time.

Outcome measures

Outcome measures
Measure	Cohort 1 n=280 Participants Dutch Parkinson's patients resident in the region of Noord-Holland whose fulfill the eligibility criteria. Interventions/Exposures to be administered: 1. PPMI (Parkinson's Progression Markers Initiative) protocol Trained physiotherapists will perform once a standardized clinical assessment to every included patient. This assessment will last for 60 minutes, and it will be done once. 2. Fox Insight self-monitoring android app and falls detector Patients will wear a smartwatch and a pendant movement sensor during day and night, for a period of 13 weeks. Additionally, a self-monitoring App on a Smartphone is used, where the patient reports when (s)he takes any PD medication. An additional, optional button allows the patient to report general feeling. Clinical assessment: During the 13 week follow-up, trained physiotherapists will perform a standardized clinical assessment, based on the PPMI protocol (www.ppmi-info.ors) for every included patient. This assessment will last for 60 minutes, and it will be done once. Fox Insight self-monitoring android app and falls detector: Patients will be asked to wear a smartwatch and a pendant movement sensor, both with triaxial accelerometers, during day and night, for a period of 13 weeks. Additionally, a self-monitoring App on a Smartphone is used, where the patient reports when (s)he takes any PD medication. An additional, optional button allows the patient to report general feeling.
Number of Medication Intake Annotations Made by Each Participant Via the Self-report App.	351 number of annotations Standard Error 217

SECONDARY outcome

Timeframe: Patients will be automatically assessed continuously during the follow-up time (up to 13 weeks after the enrollment date), 24 hours a day, 7 days a week. The analyses was limited to walking activities.

The time that the patient was active during the day is calculated automatically through the app at the smartphone. The calculation is performed by using an algorithm, which analyze the patterns of walk. This algorithm is able to predict when the patient was active in a zone above his/her usual threshold (e.g. when the patient was performing one activity that makes him/her more active than during a quiet time). At the end of the follow-up time a sum of all active hours will be done in order to measure the amount of time that the patient was active over the follow-up time.

Outcome measures

Outcome measures
Measure	Cohort 1 n=291 Participants Dutch Parkinson's patients resident in the region of Noord-Holland whose fulfill the eligibility criteria. Interventions/Exposures to be administered: 1. PPMI (Parkinson's Progression Markers Initiative) protocol Trained physiotherapists will perform once a standardized clinical assessment to every included patient. This assessment will last for 60 minutes, and it will be done once. 2. Fox Insight self-monitoring android app and falls detector Patients will wear a smartwatch and a pendant movement sensor during day and night, for a period of 13 weeks. Additionally, a self-monitoring App on a Smartphone is used, where the patient reports when (s)he takes any PD medication. An additional, optional button allows the patient to report general feeling. Clinical assessment: During the 13 week follow-up, trained physiotherapists will perform a standardized clinical assessment, based on the PPMI protocol (www.ppmi-info.ors) for every included patient. This assessment will last for 60 minutes, and it will be done once. Fox Insight self-monitoring android app and falls detector: Patients will be asked to wear a smartwatch and a pendant movement sensor, both with triaxial accelerometers, during day and night, for a period of 13 weeks. Additionally, a self-monitoring App on a Smartphone is used, where the patient reports when (s)he takes any PD medication. An additional, optional button allows the patient to report general feeling.
Time That Each Patient Was Active During the Day	72 minutes per day Standard Deviation 39

SECONDARY outcome

Timeframe: Patients will be automatically assessed during the follow-up time (up to 13 weeks after the enrollment date), 24 hours a day, 7 days a week.

Population: The collected accelerometer data turned out to be unsuitable to calculate the level of activity during the day. Algorithms produced unreliable information on activity levels and therefore no data on this outcome measure were available.

The level of activity for each patient is calculated automatically through the app at the smartphone. The calculation is performed by using the data collect with the accelerometers embedded in the smartwatch. An algorithm installed in the phone, which analyze the data collected with the smartwatch, can calculate the level of activity for each patient throughout the day.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline

The scores for autonomic dysfunctions will be obtained with the Assessment of autonomic dysfunction in Parkinson's disease (SCOPA-AUT). The total sum scores ranges from 0 to 100, in which high scores are correlated with more burden of autonomic dysfunctions in Parkinson's patients.

Outcome measures

Outcome measures
Measure	Cohort 1 n=245 Participants Dutch Parkinson's patients resident in the region of Noord-Holland whose fulfill the eligibility criteria. Interventions/Exposures to be administered: 1. PPMI (Parkinson's Progression Markers Initiative) protocol Trained physiotherapists will perform once a standardized clinical assessment to every included patient. This assessment will last for 60 minutes, and it will be done once. 2. Fox Insight self-monitoring android app and falls detector Patients will wear a smartwatch and a pendant movement sensor during day and night, for a period of 13 weeks. Additionally, a self-monitoring App on a Smartphone is used, where the patient reports when (s)he takes any PD medication. An additional, optional button allows the patient to report general feeling. Clinical assessment: During the 13 week follow-up, trained physiotherapists will perform a standardized clinical assessment, based on the PPMI protocol (www.ppmi-info.ors) for every included patient. This assessment will last for 60 minutes, and it will be done once. Fox Insight self-monitoring android app and falls detector: Patients will be asked to wear a smartwatch and a pendant movement sensor, both with triaxial accelerometers, during day and night, for a period of 13 weeks. Additionally, a self-monitoring App on a Smartphone is used, where the patient reports when (s)he takes any PD medication. An additional, optional button allows the patient to report general feeling.
Scores in Autonomic Dysfunctions Measure With the Autonomic Dysfunctions Scale	17.2 score on a scale Standard Deviation 7.9

SECONDARY outcome

Timeframe: Baseline

The Epworth sleepiness scale was used to rate the level of sleepiness during the day. The scale's scores are related to the usual duration of sleep at night and increase with relative sleep deprivation. Here, we used data from one-point assessment (baseline). Then, we can suggest that if the sample has high scores they will have a low sleep quantity. Total sum score ranges from 0 (no sleepiness at all) to 24 (excessive sleepiness).

Outcome measures

Outcome measures
Measure	Cohort 1 n=245 Participants Dutch Parkinson's patients resident in the region of Noord-Holland whose fulfill the eligibility criteria. Interventions/Exposures to be administered: 1. PPMI (Parkinson's Progression Markers Initiative) protocol Trained physiotherapists will perform once a standardized clinical assessment to every included patient. This assessment will last for 60 minutes, and it will be done once. 2. Fox Insight self-monitoring android app and falls detector Patients will wear a smartwatch and a pendant movement sensor during day and night, for a period of 13 weeks. Additionally, a self-monitoring App on a Smartphone is used, where the patient reports when (s)he takes any PD medication. An additional, optional button allows the patient to report general feeling. Clinical assessment: During the 13 week follow-up, trained physiotherapists will perform a standardized clinical assessment, based on the PPMI protocol (www.ppmi-info.ors) for every included patient. This assessment will last for 60 minutes, and it will be done once. Fox Insight self-monitoring android app and falls detector: Patients will be asked to wear a smartwatch and a pendant movement sensor, both with triaxial accelerometers, during day and night, for a period of 13 weeks. Additionally, a self-monitoring App on a Smartphone is used, where the patient reports when (s)he takes any PD medication. An additional, optional button allows the patient to report general feeling.
Sleepiness Rates in the Epworth Sleepiness Scale as a Measure of Sleep Quantity.	6.0 score on a scale Standard Deviation 4.7

Adverse Events

Cohort 1 (The Study Only Included 1 Cohort).

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Marjan Meinders

Radboudumc

Phone: +00000000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place