Measuring Parkinson's Disease Progression

NCT ID: NCT03205956

Last Updated: 2022-10-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 31 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-10-19
• Study Completion Date: 2019-10-19

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).

Conditions

Parkinson's Disease

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Levodopa

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

Carbidopa

Eligibility Criteria

Inclusion Criteria

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

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)

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 79 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Michael J. Fox Foundation for Parkinson's Research

UNKNOWN

Sponsor Role: collaborator

Kevin J. Black, MD

OTHER

Sponsor Role: lead

Responsible Party

Kevin J. Black, MD

Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Kevin J Black, MD

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Locations

Washington University School of Medicine, Movement Disorders Center

St Louis, Missouri, United States

Countries

United States

References

Black KJ, Carl JL, Hartlein JM, Warren SL, Hershey T, Perlmutter JS. Rapid intravenous loading of levodopa for human research: clinical results. J Neurosci Methods. 2003 Jul 15;127(1):19-29. doi: 10.1016/s0165-0270(03)00096-7.

Reference Type: BACKGROUND

PMID: 12865145 (View on PubMed)

Siddiqi SH, Abraham NK, Geiger CL, Karimi M, Perlmutter JS, Black KJ. The Human Experience with Intravenous Levodopa. Front Pharmacol. 2016 Jan 6;6:307. doi: 10.3389/fphar.2015.00307. eCollection 2015.

Reference Type: BACKGROUND

PMID: 26779024 (View on PubMed)

Koller JM, Vachon MJ, Bretthorst GL, Black KJ. Rapid Quantitative Pharmacodynamic Imaging with Bayesian Estimation. Front Neurosci. 2016 Apr 8;10:144. doi: 10.3389/fnins.2016.00144. eCollection 2016.

Reference Type: BACKGROUND

PMID: 27092045 (View on PubMed)

Black KJ, Acevedo HK, Koller JM. Dopamine Buffering Capacity Imaging: A Pharmacodynamic fMRI Method for Staging Parkinson Disease. Front Neurol. 2020 May 6;11:370. doi: 10.3389/fneur.2020.00370. eCollection 2020.

Reference Type: BACKGROUND

PMID: 32477245 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

009

Identifier Type: -

Identifier Source: org_study_id