MPDP: Measuring Parkinson's Disease Progression

Sponsor

Kevin J. Black, MD (Other)

Overall Status

Completed

CT.gov ID

NCT03205956

Collaborator

The Michael J. Fox Foundation for Parkinson's Research (Other)

Enrollment

Location

Arm

Actual Duration (Months)

1.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Parkinson's Disease	Drug: Levodopa	Phase 1

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).

Study Design

Study Type:

Interventional

Actual Enrollment :

31 participants

Allocation:

N/A

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.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

Official Title:

Dopamine Buffering Capacity Measured by phMRI as a Novel Biomarker of Disease Progression in PD

Actual Study Start Date :

Oct 19, 2017

Actual Primary Completion Date :

Oct 18, 2019

Actual Study Completion Date :

Oct 19, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: PD Group 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.	Drug: Levodopa 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 Names: Carbidopa

Arm

Intervention/Treatment

Experimental: PD Group

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.

Drug: Levodopa

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 Names:

Carbidopa

Outcome Measures

Primary Outcome Measures

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

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years to 79 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age 40-79 at screening
Meet accepted diagnostic criteria for Parkinson disease

Exclusion Criteria: 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)