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

140 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

Recent immunological and physiological studies have provided evidence in support of a central nervous system (CNS) lymphatic drainage system in vertebrate animals, and preliminary evidence has suggested that a similar system exists in humans. If operative, this system may have central relevance to many vascular and fluid clearance disorders such as stroke, multiple sclerosis, Parkinson's disease, and Alzheimer's disease related dementia (ADRD): diseases which represent some of the most pressing healthcare challenges of the 21st century. Evaluating this possibility will require improved, robust imaging methods sensitive to lymphatic drainage dysfunction; as such, the goal of this work is to apply novel magnetic resonance imaging approaches, optimized already for evaluating lymphatic circulation in patients with peripheral lymphatic dysfunction, to quantify relationships between physiological hallmarks of ADRD and CNS lymphatic function in humans.

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.

Is the imaging agent [11C]-PIB safe for use in humans?

The imaging agent [11C]-PIB has been studied in humans for its distribution and radiation exposure, which is important for understanding its safety. These studies help assess the balance of risks and benefits when using [11C]-PIB in PET scans. ^{1 2 3 4 5}

How does the treatment in the Brain Glymphatic Imaging for Parkinson’s Disease trial differ from other treatments for Parkinson's disease?

The treatment in this trial is unique because it focuses on imaging the brain's glymphatic system, which is a network that helps clear waste from the brain. This approach is different from traditional treatments that primarily target dopamine levels or motor symptoms in Parkinson's disease. ^{6 7 8 9 10}

What data supports the effectiveness of the drug [11C]-PIB for Parkinson's Disease?

The research highlights the use of PET imaging, which includes [11C]-PIB, as a valuable tool in studying movement disorders like Parkinson's Disease. PET imaging can help in early diagnosis, monitor disease progression, and evaluate the effectiveness of treatments, suggesting that [11C]-PIB may be useful in these aspects for Parkinson's Disease. ^{11 12 13 14 15}

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 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]

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]

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. United States pubmed.ncbi.nlm.nih.gov

The role of positron emission tomography imaging in movement disorders. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Longitudinal Changes in Neuromelanin MRI Signal in Parkinson's Disease: A Progression Marker. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Development of a clinically feasible [11C]PE2I PET method for differential diagnosis of parkinsonism using reduced scan duration and automated reference region extraction. [2020]

4. United States pubmed.ncbi.nlm.nih.gov

Significance of non-presynaptic SPECT tracer methods in Parkinson's disease. [2016]

5. United States pubmed.ncbi.nlm.nih.gov

Evaluation of novel PET ligands (+)N-[11C]methyl-3-piperidyl benzilate ([11C](+)3-MPB) and its stereoisomer [11C](-)3-MPB for muscarinic cholinergic receptors in the conscious monkey brain: a PET study in comparison with. [2016]

6. United States pubmed.ncbi.nlm.nih.gov

Visual assessment versus quantitative assessment of 11C-PIB PET and 18F-FDG PET for detection of Alzheimer's disease. [2020]

7. United States pubmed.ncbi.nlm.nih.gov

Voxel-based analysis of PET amyloid ligand [11C]PIB uptake in Alzheimer disease. [2020]

8. United States pubmed.ncbi.nlm.nih.gov

Biodistribution and radiation dosimetry of the amyloid imaging agent 11C-PIB in humans. [2022]

9. Germany pubmed.ncbi.nlm.nih.gov

In vivo amyloid imaging with PET in frontotemporal dementia. [2020]

10. England pubmed.ncbi.nlm.nih.gov

Amyloid deposition in semantic dementia: a positron emission tomography study. [2021]

11. Germany pubmed.ncbi.nlm.nih.gov

Validation of cardiac (123)I-MIBG scintigraphy in patients with Parkinson's disease who were diagnosed with dopamine PET. [2022]

12. Germany pubmed.ncbi.nlm.nih.gov

Reduced 123I-MIBG uptake in the parotid and submandibular glands in patients with Parkinson's disease identified using a quantitative semi-automatic method. [2023]

13. United States pubmed.ncbi.nlm.nih.gov

Imaging Parkinson's disease below the neck. [2023]

14. France pubmed.ncbi.nlm.nih.gov

Contributions of PET and SPECT to the understanding of the pathophysiology of Parkinson's disease. [2019]

15. Germany pubmed.ncbi.nlm.nih.gov

Diagnostic cutoff points for ¹²³I-MIBG myocardial scintigraphy in a Caucasian population with Parkinson's disease. [2022]