Utilization of Target Ranges to Treat Persons With Parkinson's Disease by Objective Measurement Using the PKG (TARGET-PwP)

Utilization of Target Ranges to Treat Persons With Parkinson's Disease by Objective Measurement Using the Personal KinetiGraph® (PKG®) Compared to Standard of Care Assessment (TARGET-PwP)- A Randomized Controlled Trial

The main objective of this study is to evaluate whether persons with Parkinson's disease (PwP) whose Parkinson's disease (PD) symptoms are uncontrolled have improved clinical patient outcomes and quality of life when managed with the aid of objective measurement and use of PKG target ranges compared to PwP treated using only standard of care (SOC) (medical history, physical examination).

Study Overview

• Status: Withdrawn
• Conditions: Parkinson Disease
• Intervention / Treatment: Device: Personal KinetiGraph® (PKG®) System; Device: Personal KinetiGraph® (PKG®) Watch

Detailed Description

This is a randomized controlled trial (RCT) to compare the value of the Personal KinetiGraph® (PKG®) System and SOC vs. the SOC alone for treatment of PwP. The study aims to evaluate clinical outcomes, quality of life outcomes, health economic benefits, duration of controlled status, and need for additional PD treatment through 3 years follow-up of PwP specifically treated to a target range when using the PKG data in the clinical management of PD in routine clinical care compared to those managed with SOC alone. All subjects will be treated by Movement Disorder Specialists and General Neurologists with expertise in PD. Both groups will be recommended to undergo treatment changes until they reach a "controlled state" that is determined by either the clinician using SOC (PKG- Group) or using recommended target ranges for PKG scores and SOC assessments (PKG+ Group). Investigators will utilize standard available treatments to manage these PwP in both groups.

• Study Type: Interventional
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 53 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Able and willing to sign a written informed consent for study participation and comply with all required follow-up visits
• Presumed to have levodopa responsive PD
• Taking levodopa for at least 30 days prior to screening visit
• Planning to continue using levodopa for PD throughout study participation
• Able to increase levodopa by a minimum of 100mg/day
• Age inclusive at the time of consent of 55-80 years
• Has not received a PKG in the last 12 months

Exclusion Criteria:

• Evidence of atypical or secondary parkinsonism
• Presence of any non-parkinsonian tremors
• Contraindication to increasing levodopa
• Requires the addition of or dose adjustment of an anti-dyskinesia medication within the next 4 months
• Those who have received advanced therapies including individuals no longer actively utilizing these therapies, or planning to receive advanced therapies in the next 6 months
• MoCA score <23 at screening visit
• Bedridden, wheelchair confined, or requires the regular use of an assistive gait device
• Predominant sleep period is during the daytime hours of 9am to 6pm (e.g. third shift worker)
• In the investigator's or sponsor's opinion, subject has any unstable or clinically significant condition that would impair the participant's ability to comply with study requirements or interfere with interpretation of the study endpoints

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PKG+ Group; For subjects in the PKG+ Group, participants will wear the PKG watch prior to all study visits in which the study investigator will review and report on the PKG prior to the visit and use the information to guide the discussion with the subject during the clinical assessment.The PKG will be used to determine if the subject is in the target range or out of the target range based on scores provided by the PKG.	Device: Personal KinetiGraph® (PKG®) System; The Personal KinetiGraph (PKG®) System consists of the following: A wrist-worn movement recording device known as the PKG® Watch, designed to acquire data on the kinematics of movement disorder symptoms over a 6-10 day period; Proprietary algorithms to translate raw movement data collected by the PKG® Watch; Data-driven report known as the PKG® The PKG® provides continuous, objective, ambulatory assessment of the treatable and disabling symptoms of Parkinson's disease including tremor, bradykinesia and dyskinesia. The PKG® also provides an assessment of daytime somnolence and an indication of propensity for impulsive behaviors.
Placebo Comparator: PKG- Group; For subjects in the PKG- Group, participants will wear the PKG watch prior to all study visits, however the investigator will not have access to the PKG report and will use standard of care to determine clinical treatment plans.	Device: Personal KinetiGraph® (PKG®) Watch; The Personal KinetiGraph (PKG®) System consists of the following: A wrist-worn movement recording device known as the PKG® Watch, designed to acquire data on the kinematics of movement disorder symptoms over a 6-10 day period; Proprietary algorithms to translate raw movement data collected by the PKG® Watch

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Patient Outcomes using Movement Disorder Specialist - Unified Parkinson's Disease Rating Scale (MDS-UPDRS)	The change in MDS-UPDRS Total score at 4 months from baseline defined as sections I, II, III (per core lab measurement) and IV in PwP. The endpoint will be compared between subjects out of target at baseline for those who are treated with SOC and PKG data (PKG+ Group) versus those who are treated per SOC alone (PKG- Group).	4 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Responder rate for total MDS-UPDRS	Percent "responders" for total MDS-UPDRS based on a minimal clinically important change of >4 points (Shulman LM, Gruber-Baldini AL, Anderson KE, et al. The Clinically Important Difference on the Unified Parkinson's Disease Rating Scale. Arch Neurol 2010: 67(1):64-70.). The Movement Disorder Specialist - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) evaluates motor and non-motor symptoms in persons with Parkinson's and consists of 4 parts with various questions and evaluations. Parts I and II (non-motor) each contain 13 questions/evaluations, Part III (motor) contains 33 and Part IV (motor) contains 6. Each question/evaluation score ranges from 0 (normal) to 4 (severe). Higher scores indicate a greater impact of Parkinson's disease symptoms (i.e., worse symptoms).	4 months
Responder rate for PKG	Percent "responders" by PKG (defined as BKS change of >2 point improvement)	4 months
Change in MDS-UPDRS motor endpoints	Change in MDS-UPDRS Part III (per core lab measurement). The Movement Disorder Specialist - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) evaluates motor and non-motor symptoms in persons with Parkinson's and consists of 4 parts with various questions and evaluations. Part III is the motor examination and contains 33 questions/evaluations. Each question/evaluation score ranges from 0 (normal) to 4 (severe). Higher scores indicate a greater impact of Parkinson's disease symptoms (i.e., worse symptoms).	4 months, 1 year, 2 years, 3 years
Change in MDS-UPDRS total	Change in MDS-UPDRS Total score from baseline. The Movement Disorder Specialist - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) evaluates motor and non-motor symptoms in persons with Parkinson's and consists of 4 parts with various questions and evaluations. Parts I and II (non-motor) each contain 13 questions/evaluations, Part III (motor) contains 33 and Part IV (motor) contains 6. Each question/evaluation score ranges from 0 (normal) to 4 (severe). Higher scores indicate a greater impact of Parkinson's disease symptoms (i.e., worse symptoms).	1 year, 2 years, 3 years
Change in MDS-UPDRS sub parts	Change in the non-motor (parts I and II) score and change in Part IV for the MDS-UPDRS from baseline. The Movement Disorder Specialist - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) evaluates motor and non-motor symptoms in persons with Parkinson's and consists of 4 parts with various questions and evaluations. Parts I and II (non-motor) each contain 13 questions/evaluations, Part III (motor) contains 33 and Part IV (motor) contains 6. Each question/evaluation score ranges from 0 (normal) to 4 (severe). Higher scores indicate a greater impact of Parkinson's disease symptoms (i.e., worse symptoms).	4 months, 1 year, 2 years, 3 years
Change in PKG Bradykinesia Score (BKS)	Change in the PKG reported BKS from baseline. A higher score represents more severe bradykinesia.	4 months, 1 year, 2 years, 3 years
Change in PKG Dyskinesia score (DKS)	Change in the PKG reported DKS from baseline. A higher score represents more severe dyskinesia.	4 months, 1 year, 2 years, 3 years
Change in Percent Time in Tremor (PTT)	Change in the PKG reported PTT from baseline, max 100%. A PTT of >1% indicates that tremor is present.	4 months, 1 year, 2 years, 3 years
Change in Fluctuation Dyskinesia score (FDS)	Change in the PKG reported FDS from baseline. The higher the score, the more severe the fluctuation, and a FDS of 7.5-13 indicates controlled fluctuations.	4 months, 1 year, 2 years, 3 years
Change in Percent Time Immobile (PTI)	Change in the PKG reported PTI from baseline, max 100%. A PTI of >5% is considered high.	4 months, 1 year, 2 years, 3 years
Change in Parkinson's Disease Questionnaire-39 questions (PDQ-39)	Change in the patient reported quality of life questionnaire PDQ-39 from baseline. The PDQ-39 is a 39-item self-report questionnaire, which assesses Parkinson's disease-specific health related quality of life issues across 8 dimensions. Each dimension total score range from 0 (never have difficulty) to 100 (always have difficulty). Lower scores reflect better quality of life.	4 months, 1 year, 2 years, 3 years
Number of Interim Visits	Number of interim visits conducted from baseline to 4 months in each arm	4 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Levodopa Equivalent Dose (LED)	Levodopa Equivalent Dose (LED) at each visit	4 months, 1 year, 2 years, 3 years
PKG Patient Survey	Analyze PKG usability with the PKG Patient reported survey. Questions are on a scale of strongly agree to strongly disagree and will be patient reported information related to their use of the PKG watch. Both treatment groups will be administered the survey and scores will be aggregated by group and compared.	4 months, 1 year, 2 years, 3 years
Healthcare Utilization	Rate of protocol defined adverse events affecting health care utilization from baseline	4 months, 1 year, 2 years, 3 years
Potential Contraindications	Rate of protocol defined adverse events and potential contraindications for increasing dopaminergic therapy from baseline	4 months, 1 year, 2 years, 3 years
Lifestyle Factors Impacted by PD	Rate of protocol defined lifestyle factors impacted by PD	4 months, 1 year, 2 years, 3 years
Work Productivity and Activity Impairment	Change in Work Productivity and Activity Impairment Questionnaire (WPAI) from baseline. The WPAI Questionnaire includes questions regarding impacts to work productivity due to PD symptoms.	4 months, 1 year, 2 years, 3 years
PKG scores	Proportion of enrolled subjects in PKG+ group who are either unable to be brought into the target range or unable to be brought to a BKS ≤26. A higher score represents more severe bradykinesia.	4 months, 1 year, 2 years, 3 years

Collaborators and Investigators

• Sponsor: Global Kinetics Corporation
• Investigators: Principal Investigator: Raja Mehanna, MD, The University of Texas Health Science Center, Houston

Publications and helpful links

General Publications

• Pahwa R, Isaacson SH, Torres-Russotto D, Nahab FB, Lynch PM, Kotschet KE. Role of the Personal KinetiGraph in the routine clinical assessment of Parkinson's disease: recommendations from an expert panel. Expert Rev Neurother. 2018 Aug;18(8):669-680. doi: 10.1080/14737175.2018.1503948. Epub 2018 Jul 26.
• Shulman LM, Gruber-Baldini AL, Anderson KE, Fishman PS, Reich SG, Weiner WJ. The clinically important difference on the unified Parkinson's disease rating scale. Arch Neurol. 2010 Jan;67(1):64-70. doi: 10.1001/archneurol.2009.295.

Helpful Links

• Sponsor website

Study record dates

Study Major Dates

• Study Start (Anticipated): June 1, 2020
• Primary Completion (Anticipated): April 1, 2022
• Study Completion (Anticipated): April 1, 2026

Study Registration Dates

• First Submitted: May 1, 2020
• First Submitted That Met QC Criteria: May 5, 2020
• First Posted (Actual): May 8, 2020

Study Record Updates

• Last Update Posted (Actual): February 1, 2021
• Last Update Submitted That Met QC Criteria: January 27, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: Objective Measurement; Personal KinetiGraph® (PKG®) System
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease
• Other Study ID Numbers: Study 004

Drug and device information, study documents

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