Measuring Parkinson's Disease Progression
- Registration Number
- NCT03205956
- Lead Sponsor
- Kevin J. Black, MD
- Brief Summary
The Measuring Parkinson's Disease Progression study aims to use MRI scans and a controlled dose of levodopa to find a biomarker (objective measurement) of Parkinson's disease (PD). Biomarkers would help determine the effectiveness of therapies in slowing or stopping PD progression, and accelerate the pace of research.
- Detailed Description
Early in the course of Parkinson's disease, a small dose of levodopa (L-DOPA) provides benefit for many hours. The body responds as if the levodopa in the plasma filled a reservoir and then slowly leaked out to produce benefit. With disease progression, even though the same amount of levodopa circulates in the blood, the benefit wears off much faster, as if the reservoir had become leakier. This wearing off of benefit can be characterized by a single number, the effect site rate constant Ke. On average, patients with more severe disease and longer disease duration have a larger ("leakier") Ke when the response to drug is measured using clinical features like tapping speed. Unfortunately, clinical measurements are influenced by confounding factors such as patient fatigue and comfort. A direct, objective brain measure of response to levodopa may improve the reliability of this measurement. Fortunately, we can assess the effect of levodopa on the brain directly, using an MRI machine to measure blood flow in different parts of the brain. For instance, the midbrain has a robust blood flow response to a single, clinically sensible dose of levodopa. This study's goal is to validate MRI measurement of Ke in the brain as an objective, quantitative measure of disease severity in PD. We will do this by comparing MRI-based Ke values from people with PD across a wide range of disease duration and severity. In a subgroup of participants, we will do this measurement twice, once before treatment and once after 6 weeks of treatment with carbidopa-levodopa (Sinemet® and other brand names).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 31
- Age 40-79 at screening
- Meet accepted diagnostic criteria for Parkinson disease
Key exclusion criteria:
- Deep brain stimulator (DBS)
- Pregnancy
- Patients taking a dopamine antagonist (like quetiapine) or dopamine partial agonist (like aripiprazole)
- Metal in the head or eye, or other contraindication to MRI
- Claustrophobia
- Serious neurologic disease other than PD
- Head trauma with loss of consciousness for more than 5 minutes
- Severe or unstable systemic illness
- Certain psychiatric illnesses (dementia, psychosis, current major depression)
- Current alcohol use disorder
- Subjects who feel that going without nicotine for 3-4 hours would be uncomfortable
- Currently taking an extended-release formulation of a dopamine agonist (like Mirapex ER or Requip XL)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description PD Group Levodopa A broad range of Parkinson's disease severity and disease duration. Some subjects will not be treated currently with levodopa, and thus likely will be early in the disease process.
- Primary Outcome Measures
Name Time Method Ke measured by phMRI 2 hours Effect site rate constant measured by serum levodopa concentrations and regional cerebral blood flow. Note, there are no outcome measures relevant to clinical care. This is not a placebo-controlled treatment study.
- Secondary Outcome Measures
Name Time Method Side effect ratings 2 hours Nausea/vomiting, sleepiness, dizziness or lightheadedness, and overall feeling poorly or well, are each measured on a horizontal visual analog scale before and at the end of the i.v. levodopa infusion
Trial Locations
- Locations (1)
Washington University School of Medicine, Movement Disorders Center
🇺🇸Saint Louis, Missouri, United States