Brain Glymphatic Imaging for Parkinson’s Disease

Overseen By Manus J Donahue, Ph.D.

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Vanderbilt University Medical Center

Must not be taking: Stimulants, Chemotherapy

Disqualifiers: Unstable diabetes, Stroke, Claustrophobia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the potential connection between the brain's lymphatic system (a fluid drainage network) and Parkinson's disease, a condition affecting movement. Researchers use a special imaging technique with a tracer called [11C]-PIB (also known as C-11 PiB or Pittsburgh Compound B) to investigate this link. The goal is to determine if issues with this drainage system relate to symptoms or brain changes associated with Parkinson's. Individuals with Parkinson's who have mild cognitive impairment (trouble with memory and thinking) and are willing to undergo PET and MRI scans may be suitable candidates for this trial. As an Early Phase 1 trial, this study aims to understand how the imaging technique functions in people, offering participants a chance to contribute to groundbreaking research.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. However, it does exclude participants with recent stimulant use, so you may need to avoid stimulants.

What prior data suggests that this imaging method is safe for humans?

Research shows that C-11 PiB, the treatment used in this trial, is generally safe for humans. C-11 PiB is commonly used in PET scans to visualize certain brain features, particularly in conditions like Alzheimer's disease.

Previous studies have safely used C-11 PiB in individuals with Parkinson's and Alzheimer's, suggesting no major safety concerns. Its safe use in other medical settings further supports its safety.

This trial is in an early phase, so safety remains a major focus. Although detailed information on side effects might not yet be available, past research on C-11 PiB indicates it is a safe option for imaging. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the trial for [11C]-PIB, also known as C-11 PiB, because it offers a novel way to study brain function in Parkinson’s patients, particularly those with mild cognitive impairment (MCI). Unlike current treatments that primarily address motor symptoms, this method uses a radiotracer to image the brain's glymphatic system, potentially revealing new insights into how the brain's waste clearance system might be implicated in Parkinson's disease. By understanding this mechanism better, the trial could lead to the development of more targeted therapies that address cognitive aspects of the disease, which are often overlooked.

What evidence suggests that this trial's treatments could be effective for Parkinson's disease?

Research has shown that C-11 PiB is a special substance used in brain scans to detect amyloid-beta plaques, often found in people with Alzheimer's disease. In this trial, participants with Parkinson's disease and mild cognitive impairment (MCI) will undergo a C-11 PiB PET scan. Among those with Parkinson's disease who have dementia, about 20-30% show increased PiB binding. This binding relates to genetic factors and lower levels of certain proteins in brain fluid, which are linked to memory and thinking problems. Using C-11 PiB in imaging helps researchers visualize these plaques, providing insights into brain function and potential issues. While primarily used in Alzheimer's research, it also offers important information about brain changes in Parkinson's disease related to memory and thinking issues. ^{2 3 5 6 7}

Who Is on the Research Team?

Manus J Donahue, Ph.D.

Principal Investigator

Vanderbilt University Medical Center

Are You a Good Fit for This Trial?

This trial is for individuals diagnosed with Parkinson's Disease or healthy controls willing to undergo PET and MRI imaging. It excludes those who have used stimulants recently, have unstable diabetes, a history of stroke, claustrophobia, prior chemotherapy for cancer treatment, traumatic brain injury, or any unstable medical condition.

Inclusion Criteria

I am willing to undergo PET and MRI scans.

I have been diagnosed with Parkinson's Disease.

Exclusion Criteria

I have had a stroke before.

You have used stimulant drugs recently.

Any unstable medical condition

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

MRI Scans

Participants undergo 1-2 non-invasive MRI scans at a field strength of 3 Tesla, each lasting 60-90 minutes.

1-2 weeks

1-2 visits (in-person)

PET Scans

Patient volunteers undergo a C-11 PiB PET scan performed by a certified PET technologist.

1 week

1 visit (in-person)

Anesthesia and DTI MRI

Measurements of glymphatic function are performed before and during general anesthesia using a modified DTI MRI approach.

1 week

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after imaging procedures.

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• [11C]-PIB
• C-11 PiB

Trial Overview [11C]-PIB is being tested as part of an effort to improve imaging methods that can detect issues in the brain's lymphatic drainage system. This could be important for understanding and treating conditions like Parkinson's disease and Alzheimer's related dementia.

How Is the Trial Designed?

Group I: Parkinson's Disease participants with MCI Experimental Treatment 1 Intervention

Patient volunteers will also undergo a C-11 PiB PET scan. This procedure utilizes a common radiotracer that is used routinely in clinical PET scans and will be purchased here from PETNET and certified for human use. All PET scans will be performed by a certified PET technologist at the Vanderbilt University Institute of Imaging Science.

Who Is Running the Clinical Trial?

Vanderbilt University Medical Center

Lead Sponsor

Trials

922

Recruited

939,000+

Published Research Related to This Trial

In a study involving 30 participants (11 with semantic dementia, 9 with Alzheimer's disease, and 10 healthy controls), only a minority of early-onset semantic dementia patients showed amyloid-β deposition, while late-onset semantic dementia patients were PIB-negative, suggesting a lack of Aβ accumulation in this group.

The findings indicate that amyloid-β deposition is not associated with late-onset semantic dementia, and while some early-onset patients may exhibit Aβ deposition, they do not present the typical memory or visuospatial deficits seen in Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amyloid deposition in semantic dementia: a positron emission tomography study. Brown, EE., Graff-Guerrero, A., Houle, S., et al.[2021]

In a study involving 17 Alzheimer's disease (AD) patients and 11 healthy controls, PET imaging with the tracer [(11)C]PIB showed significantly increased uptake in several brain regions, indicating higher amyloid accumulation in AD patients.

The most notable increases in [(11)C]PIB uptake were found in the frontal cortex (163% of control mean) and posterior cingulate (146%), aligning with known patterns of amyloid pathology in Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Voxel-based analysis of PET amyloid ligand [11C]PIB uptake in Alzheimer disease. Kemppainen, NM., Aalto, S., Wilson, IA., et al.[2020]

Positron emission tomography (PET) and single photon emission computed tomography (SPECT) are effective noninvasive imaging techniques that can quantify the extent of dopaminergic denervation in Parkinson's disease (PD), showing a significant correlation between decreased striatal uptake of radiotracers and the severity of motor symptoms.

These imaging methods can also assess changes in dopamine receptor density and the effects of treatments like dopaminergic medication or surgical interventions, although they currently have limitations in differentiating PD from other similar neurodegenerative disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Contributions of PET and SPECT to the understanding of the pathophysiology of Parkinson's disease. Thobois, S., Guillouet, S., Broussolle, E.[2019]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/17855149/

[(11)C]-PIB imaging in patients with Parkinson's disease We investigated five apparently cognitively normal PD patients with [(11)C]-PIB PET. The results were compared to 16 patients with AD and six healthy controls ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3775684/

component analysis of PiB distribution in Parkinson and ... Elevated PiB binding occurs in 20%–30% of patients with PD with dementia and is associated with the APOE ε4 gene, lower CSF Aβ42,10 and cognitive decline.

3. sciencedirect.com sciencedirect.com/topics/agricultural-and-biological-sciences/pittsburgh-compound-b

Pittsburgh Compound B - an overview Pittsburgh Compound B (11C-PIB) is a neutral derivative of the histological dye thioflavin T that in AD brain slices shows nanomolar affinity for neuritic β- ...

4. mdpi.com mdpi.com/1420-3049/25/4/977

PET Radiopharmaceuticals for Alzheimer's Disease and ... It showed a combination of favorable pharmacokinetics as PiB, the highest brain clearance 5 times faster than at 30 min and a high binding affinity to Aβ ...

5. pubs.acs.org pubs.acs.org/doi/10.1021/acsptsci.4c00149

Screening of [18F]Florbetazine for Aβ Plaques and a Head-to ... Screening of [18F]Florbetazine for Aβ Plaques and a Head-to-Head Comparison Study with [11C]Pittsburgh Compound-B ([11C]PiB) in Human Subjects.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3542972/

Using Pittsburgh Compound B for In Vivo PET Imaging of ... Here, we will discuss the application of one of the most broadly studied and widely used Aβ imaging agents, Pittsburgh Compound-B (PiB).

7. jneurosci.org jneurosci.org/content/27/39/10365

In Vitro Characterization of Pittsburgh Compound-B ... [11C]-Pittsburgh compound B ([11C]-PIB) is a thioflavin-T derivative that has allowed in vivo Aβ burden to be quantified using positron ...