Measuring Parkinson's Disease Progression
Condition: Parkinson's Disease
MeSH terms: Parkinson Disease; Disease Progression
Study type: Interventional
Phase: Phase 1

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).
    

Intervention name(s): Levodopa
Intervention type(s): Drug
Intervention description(s): At least 1 hour after 200mg carbidopa p.o., each subject will receive an intravenous solution of levodopa in saline at a rate based on age and body mass according to the "final dose" described in Black et al 2003.The total dose for a 70-year-old, 70kg subject will be approximately 65mg.
Subjects with untreated PD will then take 6 ± 1 weeks of clinically dosed oral carbidopa-levodopa tablets for clinical purposes and then repeat the carbidopa plus intravenous levodopa dose as above.
Other intervention name(s): Carbidopa
Intervention MeSH terms: Levodopa; Carbidopa
Intervention model: Single Group Assignment
Intervention model description: All participants receive oral carbidopa before, and i.v. levodopa during brain imaging, to measure regional cerebral blood flow responses to levodopa.
Masking: None (Open Label)
Primary purpose: Other
Keywords: Parkinson's disease; PD; levodopa