Parkinson's DiseasePhase 1MPDPNCT03205956
Measuring Parkinson's Disease Progression
A Phase 1 study testing Levodopa in people with Parkinson's Disease, run by Kevin J. Black, MD at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 40 to 79 years
- Conditions the study is for
- Parkinson's Disease
- What is being tested?
- Levodopa
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Oct 2017to 19 Oct 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 79 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 40-79 at screening
- Meet accepted diagnostic criteria for Parkinson disease
Who cannot join
- 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
Show all 12Show fewer
- 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)
Trial locations and contacts
1 site in 1 country.
United States1 site
Washington University School of Medicine, Movement Disorders Center
St Louis, Missouri, 63110
About this study
Official title: Dopamine Buffering Capacity Measured by phMRI as a Novel Biomarker of Disease Progression in PD
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.
Read the 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
- Being tested
- Levodopa
- Keywords
- Parkinson's disease, PD, levodopa
- Medical subject headings
- Parkinson Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LevodopaDrug
Also called Carbidopa
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.
| Study group | Role | What they receive |
|---|---|---|
| PD Group | Experimental | 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. Receives: Drug: Levodopa |
What is being measured
The primary outcome is the main question the study is designed to answer.
Ke measured by phMRI
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.
Measured: 2 hours
Secondary outcomes (1)
Side effect ratings
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
Measured: 2 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jul 2017
- Study start19 Oct 2017
- Primary completion18 Oct 2019
- Study completion19 Oct 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Parkinson's DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- 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)
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kevin J. Black, MD
- Sponsor type
- University, hospital or other
- Collaborators
- Michael J. Fox Foundation for Parkinson's Research
- Responsible party
- Sponsor-investigator, Kevin J. Black, MD, Washington University School of Medicine
- Investigators
- Kevin J Black, MD, Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03205956
- Sponsor's protocol ID
- 009
- Acronym
- MPDP
- Status last verified
- Oct 2022
- First submitted
- 29 Jun 2017
- Last updated
- 14 Oct 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: We will publicly share a fully anonymized set of linked data from this study. No protected health information (PHI) will be shared.
Publications
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.
PubMed 12865145Siddiqi 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.
PubMed 26779024Koller 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.
PubMed 27092045Black 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.
PubMed 32477245
Study at a glance
From the registry record, last updated by the sponsor on 14 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dopamine Buffering Capacity Measured by phMRI as a Novel Biomarker of Disease Progression in PD
- ClinicalTrials.gov ID
- NCT03205956
- Acronym / sponsor ID
- MPDP / 009
- Conditions
- Parkinson's Disease
- Keywords
- Parkinson's disease, PD, levodopa
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- Kevin J. Black, MDUniversity, hospital or other
- Collaborators
- Michael J. Fox Foundation for Parkinson's Research
- Study start
- 19 Oct 2017 (actual)
- Primary completion
- 18 Oct 2019 (actual)
- Study completion
- 19 Oct 2019 (actual)
- First posted
- 2 Jul 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- All participants receive oral carbidopa before, and i.v. levodopa during brain imaging, to measure regional cerebral blood flow responses to levodopa.
| Arm | Type | Receives |
|---|---|---|
| PD Group | Experimental | Drug: LevodopaA 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. |
Who may qualify
- Ages
- 40 to 79 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Age 40-79 at screening
- Meet accepted diagnostic criteria for Parkinson disease
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LevodopaAlso: CarbidopaAt 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. | Drug | PD Group |
Primary outcome
Ke measured by phMRI
Time frame: 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.
1 secondary outcome
Side effect ratings
Time frame: 2 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Oct 2022.
- Background: PubMed 12865145Black 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.
- Background: PubMed 26779024Siddiqi 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.
- Background: PubMed 27092045Koller 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.
- Background: PubMed 32477245Black 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.
- Individual participant dataSharing planned: Yes. We will publicly share a fully anonymized set of linked data from this study. No protected health information (PHI) will be shared.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kevin J Black, MD principal investigator
Washington University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Levodopa in people with Parkinson's Disease, run by Kevin J. Black, MD at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Ke measured by phMRI (time frame: 2 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03205956, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Oct 2022.