Real-Time Levodopa Level Monitoring in Parkinson Disease

Study Overview
=================
Brief Summary
-----------------
This project aims to develop a minimally invasive microneedle sensor to monitor levodopa levels in real time. We will test the accuracy, tolerability, and safety of this device in people with Parkinson disease.

Detailed Description
-----------------
People with Parkinson disease (PD) lack the chemical dopamine, which is important for movement. Levodopa replaces dopamine and restores normal motor function in PD. Early in the disease stages, people with PD benefit significantly from levodopa. However, as PD progresses, the brain loses more dopamine-producing cells, which causes motor complications and unpredictable responses to levodopa. To maintain control of symptoms over time, levodopa doses must be increased and given at increasingly shorter intervals. The optimal levodopa regimen is different for each person and may vary from day-to-day, depending on a variety of internal and external factors including meal consumption, activity level, and other lifestyle variances. Currently, clinicians assess levodopa's benefit by the patient's testimony and by clinical exam. However, these methods may not adequately represent the severity or range of complications experienced by the PD patient. Thus, it can be difficult to determine the optimal levodopa treatment regimen, which can cause suboptimal disease management and side effects. This project aims to develop a continuous, minimally invasive microneedle device placed on the skin (the Levodopameter) designed to continuously measure levodopa levels in real time, with the future goals of identifying an individualized treatment regimen for people with PD to improve disease management. We will compare levodopa levels measured by the Levodopameter to the impractical and expensive gold standard high-performance liquid chromatography (HPLC) analysis of plasma levodopa levels. We will first test the device after administering oral carbidopa/levodopa in 10 participants with PD. After that portion of the study is completed and safety confirmed, we will test the device in 10 participants with PD after administering carbidopa and intravenous levodopa. We will also evaluate the device's safety and tolerability. The long-term goal of this device is to allow PD patients to take proactive measures to assess and maintain an optimal, personalized levodopa regimen, similar to diabetes care in which diabetic patients periodically self-monitor their glucose and adjust their insulin regimen accordingly.

Official Title
-----------------
Real-Time Levodopa Monitoring for Improved Management of Parkinson Disease

Conditions
-----------------
Parkinson Disease

Intervention / Treatment
-----------------
* Device: Levodopameter


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Participants must meet the Movement Disorders Society (MDS) diagnostic criteria for clinically established Parkinson disease. Able to provide signed informed consent (in English or Spanish) Mild, moderate, or severe Parkinson disease, able to ambulate (Hoehn and Yahr stages I-IV) Taking instant release oral carbidopa/levodopa therapy Either not taking, or on stable doses of any of the following antiparkinsonian medications: dopamine agonists, monoamine oxidase B (MAO-B) inhibitors or catecholamine O-methyl transferase (COMT) inhibitors Exclusion Criteria: Other neurological conditions including but not limited to stroke, dementia (including Parkinson disease dementia), or traumatic brain injury Co-existent major psychiatric disease Uncontrolled, active medical conditions (e.g., heart, kidney, or liver failure, diabetes, etc.) Status post deep brain stimulation (DBS) device placement Any other condition, that in the opinion of the investigators, would place the participant at risk.

Ages Eligible for Study
-----------------
Minimum Age: 40 Years
Maximum Age: 85 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Interventional Model Description: Participants will receive either oral carbidopa and either oral or intravenous levodopa and the minimally invasive experimental device will measure levodopa levels in interstitial fluid, which will be compared to plasma levodopa levels measured using high-performance liquid chromotography.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Levodopameter<br>During the single study visit, participants will receive either: 1) two separate doses of oral levodopa in a dose equivalent to their home regimen with one dose of carbidopa in a 1:10 ratio and one dose of carbidopa in a 1:4 ratio (carbidopa:levodopa) ratio; or will receive 2) one dose of oral carbidopa 100mg followed by intravenous levodopa in 1.2mg/kg dose. levodopa The Levodopameter microneedle sensor device will serially measure interstitial fluid levodopa levels and blood will be simultaneously collected from an intravenous line for high-performance liquid chromotography analysis of plasma levodopa levels. | Device: Levodopameter<br>* The device is a microneedle sensor that can detect levodopa levels in the interstitial fluid.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Levodopa Levels | Data analysis from this first-of-its-kind microneedle levodopa monitoring device is necessarily exploratory and descriptive. We will assess the Levodopameter's feasibility and accuracy by comparing its interstitial fluid levodopa measurements to plasma levodopa levels analyzed by high-performance liquid chromatography. | through study completion, an average of 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient Acceptability of Levodopameter | Participants will rate acceptability of the Levodopameter using a symmetric Likert-style questionnaire ranging from 1 (strongly disagree) to 5 (strongly agree) to rate the device's comfort, ease of wear, and other qualities. Averaged acceptability ratings of 4 and higher (agree or strongly agree) would indicate the participant's agreement on the device acceptability. | through study completion, an average of 12 months | 
| Device Safety | The investigators will monitor for and categorize the adverse events related to the device using the will be classified using the current version of the Common Terminology Criteria for Adverse Events. | through study completion, an average of 12 months |