SBIR-STTR Award

The objective is to design, build, and clinically assess Kinesia-D", a compact, portable, wireless movement disorder system with continuous monitoring capabilities to detect and quantify the severity of levodopa-induced choreatic dyskinesia, or irregular rapid involuntary movements, in Parkinson's disease (PD). Disease incidence affects over 1,000,000 people in the United States and continues to increase. While significant strides have been made in the management of PD motor symptoms, treatment side effects such as dyskinesia pose a key therapeutic challenge. Approximately 30% of patients diagnosed with PD exhibit levodopa-induced dyskinesia within 5 years of treatment and 59-100% by 10 years. Healthcare costs are directly correlated with dyskinesia severity. Annual costs associated with a patient exhibiting severe dyskinesia are $16,000 more than a patient with no symptoms. Assessment of dyskinesia impairment is typically performed during office visits using subjective measures. These rating scales are limited by relying on patient recall and may not accurately reflect the duration, severity, and disability fluctuations of dyskinesia experienced in the home setting throughout the day. Therefore, current dyskinesia evaluation methods may limit the clinician's ability to effectively adjust medication dose for both optimal reduction of PD motor symptoms AND levodopa-induced dyskinesia. The Kinesia-D proposal will leverage CleveMed motion sensor technology to create a stand-alone portable system to capture and quantify therapy-induced choreatic dyskinesia through a clinical study. It is hypothesized that this project will successfully 1) capture quantitative variables highly correlated to choreatic dyskinesia, 2) detect the presence or absence of choreatic dyskinesias regardless of background voluntary movements, and 3) demonstrate feasibility for automated detection of levodopa-induced dyskinesia. .

Public Health Relevance:
Upon initial onset of Parkinson's disease (PD), Levodopa is the most-widely used and effective treatment of PD motor symptoms;however, medication dose side effects can cause debilitating choreatic dyskinesia, or irregular brief rapid movements. A reliable method for detecting and monitoring the severity of dyskinesia outside of the clinical setting would be highly valuable both for aiding clinicians in optimizing medication regimens for patients and for monitoring dyskinesia in clinical trials for advanced PD. Kinesia-D will address the growing concern of Medicare usage cost in the aging adult population and over 1.5 million people in the U.S. living with PD by providing a cost effective dyskinesia assessment method that is not constrained to clinical office visits, will potentially facilitate participation of under- represented rural patient populations in clinical trials, and may show early detection of drug adverse events such as dyskinesia in clinical trials to potentially impact trial designs for novel therapeutic PD treatments.

Thesaurus Terms:
(--)-2amino-3-)3,4-Dihydroxyphenyl)Propanoic Acid;(--)-3-(3,4-Dihydroxyphenyl)-L-Alanine;21+ Years Old;3,4-Dihydroxyphenethylamine;3-Hydroxy-L-Tyrosine;4-(2-Aminoethyl)-1,2-Benzenediol;Abnormal Movements;Activities Of Daily Living;Activities Of Everyday Life;Address;Adult;Adverse Experience;Adverse Effects;Adverse Event;Affect;Aged 65 And Over;Aging;Algorithms;Body Weight Decreased;Bradykinesia;Care Givers;Caregivers;Chorea;Choreic Movement;Choreiform Movement;Chronic;Clinical;Clinical Research;Clinical Study;Clinical Trials;Clinical Trials Design;Clinical Trials, Unspecified;Computer Programs;Computer Software;Custom;Depression;Detection;Development;Diagnosis;Disease;Disorder;Dopamine;Dose;Drug Therapy;Drugs;Dyskinesia Syndromes;Dyskinesias;Dyskinetic Syndrome;Early Diagnosis;Elderly;Elderly, Over 65;Equilibrium;Evaluation;Exhibits;Fatigue;Feedback;Health Care Costs;Health Costs;Health Insurance For Aged And Disabled, Title 18;Health Insurance For Aged, Title 18;Health Insurance For Disabled Title 18;Healthcare Costs;History;Home;Home Environment;Human, Adult;Hydroxytyramine;Idiopathic Parkinson Disease;Impairment;Incidence;Individual;Investigators;Involuntary Movements;L-3,4-Dihydroxyphenylalanine;L-Dopa;Lack Of Energy;Levodopa;Lewy Body Parkinson Disease;Life;Measures;Medicare;Medication;Mental Depression;Methods;Minor;Modification;Monitor;Motion;Motor;Motor Manifestations;Movement;Movement Disorder Syndromes;Movement Disorders;Muscle Rigidity;Office Visits;Paralysis Agitans;Parkinson;Parkinson Disease;Parkinson's;Parkinson's Disease;Parkinsons Disease;Patient Monitoring;Patients;Pattern;Pharmaceutic Preparations;Pharmaceutical Preparations;Pharmacotherapy;Phase;Population;Primary Parkinsonism;Process;Qol;Quality Of Life;Recording Of Previous Events;Regimen;Reporting;Research;Research Personnel;Researchers;Rigidity;Rigidity, Muscular;Rural;Senescence;Severities;Social Isolation;Software;Symptoms;System;System, Loinc Axis 4;Technology;Therapeutic;Time;Title 18;Treatment Side Effects;Treatment Outcome;Tremor;United States;Weight Loss;Weight Reduction;Wireless Technology;Abnormal Involuntary Movement;Adult Human (21+);Advanced Age;Balance;Balance Function;Base;Beta-(3,4-Dihydroxyphenyl)-L-Alanine;Body Movement;Body Weight Loss;Clinical Decision-Making;Clinical Investigation;Computer Program /Software;Computer Program/Software;Cost;Cost Effective;Daily Living Functionality;Data Exchange;Design;Designing;Disability;Disease /Disorder;Disease/Disorder;Drug /Agent;Drug/Agent;Early Detection;Effective Therapy;Elders;Exhaustion;Experience;Functional Ability;Functional Capacity;Geriatric;Health Insurance For Disabled;Late Life;Later Life;Motor Control;New Therapeutics;Next Generation Therapeutics;Novel Therapeutics;Older Adult;Older Person;Patient Population;Physician Office Visit;Prototype;Senescent;Senior Citizen;Sensor;Side Effect;Success;Therapy Adverse Effect;Treatment Adverse Effect;Wireless;Wt-Loss

The objective is to develop and clinically assess Kinesia-D", a wireless, ergonomic, and portable movement disorder technology designed for continuous monitoring of levodopa-induced dyskinesia (LID) and medication state in Parkinson's disease (PD). Motor symptoms can be ameliorated pharmacologically with the dopamine precursor, levodopa. While significant strides have been made in the management of PD, balancing motor improvement with treatment dyskinesia side effects (brief, rapid, irregular movements) associated with chronic use poses a key therapeutic challenge. Approximately 30 percent of patients exhibit LID within 5 years of treatment and 59-100 percent by 10 years. LID significantly impact quality of life through exhaustion and fatigue, social isolation, and depression. Healthcare costs are substantially greater with increased LID severity. Yearly costs increase over $16,000 when comparing a PD patient with severe LID to one with no side effects. The value of this application is tremendous in that existing clinical tools for capturing he levodopa dose response are completely reliant on in-clinic testing and/or the patient's subjective assessment of and ability to distinguish between PD tremor, dyskinesias, and voluntary movements throughout the day. Kinesia-D will not only objectively and accurately rate dyskinesia and tremor severity on a continuous scale independent of each other and activities of daily living, but also generate reports on levodopa response medication states: OFF (no PD symptomatic improvement), ON (PD symptomatic improvement), and ON with dyskinesia. This Phase II application will develop a system which can continuously rate dyskinesia severity throughout the day independent of activities of daily living while also allowing comfortable wear with minimal burden. This will be seamlessly integrated with existing tremor scoring algorithms for simultaneous assessment of PD symptom improvement and LID occurrence. These scores will be used to determine dyskinesia severity and medication state. Reports will automatically be generated and transmitted to the clinician via a broadband-enabled tablet computer residing in the patient's home to guide titration of levodopa treatment. A reliable method for detecting and monitoring the severity of dyskinesia in an ambulatory setting would be highly valuable both for aiding clinicians in optimizing patient medication regimens and the massive pharmaceutical industry for developing new PD drugs and for post market surveillance. Kinesia-D will first be validated in a home study by showing high correlations to the patient dyskinesia diary and then be used to compare therapy titration patient outcome using the Kinesia-D system versus traditional methods. Clinical outcome measures will be based on improved quality of life and motor scores and increased hours in the ON medication state without dyskinesia. We hypothesize that the commercial Kinesia-D system will continuously quantify dyskinesia severity during activities of daily living, improve patient outcomes by balancing PD motor symptom and dyskinesia side effect response to levodopa, and reduce healthcare and clinical drug trial costs.

Public Health Relevance:
Levodopa is the most widely used medication to treat Parkinson's disease; however, levodopa-induced dyskinesia (brief, rapid, irregular movements) is the primary adverse effect associated with chronic use, occurs in approximately 30 percent of patients within 5 years of treatment and 59-100 percent by 10 years, significantly impacts quality of life, and can increase healthcare costs by over $16,000 per year for patients that exhibit levodopa- induced dyskinesia. Existing tools available to clinicians for assessing dyskinesia severity in response to adjustments in PD medication are significantly limited in that 1) the pattern and severity of dyskinesia vary substantially over time and during different activities, 2) home dyskinesia diaries rely entirely on the patient's subjective perception of their medication state and their level of compliance, and 3) patients may underestimate the severity of the dyskinesia and have difficulty distinguishing between dyskinesia, tremor, and normal voluntary movements. Kinesia-D" will address these limitations through the development of a wireless, ergonomic, and portable movement disorder technology designed for continuous monitoring of levodopa induced dyskinesia and medication state in Parkinson's disease independent of voluntary movement associated with activities of daily living as well as a cloud-based telemedicine interface for remote therapy titration for the geographically disparate PD population.

Public Health Relevance Statement:
Levodopa is the most widely used medication to treat Parkinson's disease; however, levodopa-induced dyskinesia (brief, rapid, irregular movements) is the primary adverse effect associated with chronic use, occurs in approximately 30 percent of patients within 5 years of treatment and 59-100 percent by 10 years, significantly impacts quality of life, and can increase healthcare costs by over $16,000 per year for patients that exhibit levodopa- induced dyskinesia. Existing tools available to clinicians for assessing dyskinesia severity in response to adjustments in PD medication are significantly limited in that 1) the pattern and severity of dyskinesia vary substantially over time and during different activities, 2) home dyskinesia diaries rely entirely on the patient's subjective perception of their medication state and their level of compliance, and 3) patients may underestimate the severity of the dyskinesia and have difficulty distinguishing between dyskinesia, tremor, and normal voluntary movements. Kinesia-D" will address these limitations through the development of a wireless, ergonomic, and portable movement disorder technology designed for continuous monitoring of levodopa induced dyskinesia and medication state in Parkinson's disease independent of voluntary movement associated with activities of daily living as well as a cloud-based telemedicine interface for remote therapy titration for the geographically disparate PD population.

Project Terms:
Achievement; Activities of Daily Living; Address; Adverse effects; Algorithms; base; Chronic; Clinic; Clinical; clinical decision-making; Clinical Trials; Computer software; Computers; cost; Data Reporting; design; Detection; Development; diaries; Discrimination (Psychology); Dopamine; Dose; Drug Industry; Dyskinetic syndrome; Equilibrium; ergonomics; exhaustion; Exhibits; experience; Fatigue; foot; Hand; Health Care Costs; Healthcare; Home environment; Home visitation; Hour; House Call; Human; improved; Laboratories; Levodopa; Limb structure; Measures; Medication-Induced Dyskinesia; Mental Depression; Methods; Monitor; Motion; Motor; Movement; Movement Disorders; Outcome; Outcome Measure; Output; Parkinson Disease; Patients; Pattern; Perception; Performance; Pharmaceutical Preparations; Pharmacotherapy; Phase; Population; post-market; programs; prototype; Quality of life; Regimen; Reporting; research study; response; Rotation; Sample Size; sensor; Severities; Social isolation; stem; symptomatic improvement; Symptoms; System; Tablets; Technology; Telemedicine; Testing; Therapeutic; Time; Titrations; tool; Tremor; Update; Wireless Technology