Quantitative Imaging of Brain Glymphatic Function in Humans

NCT ID: NCT04768101

Last Updated: 2025-06-17

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 140 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-04-15
• Study Completion Date: 2025-12-31

Brief Summary

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.

Detailed Description

The proposal involves magnetic resonance imaging (MRI) of healthy volunteers and patient volunteers suffering from Parkinson's disease. As part of the research study, volunteers will undergo 1-2 non-invasive MRI scans at a field strength of 3 Tesla. Each scan session will last 60-90 minutes, and will include the time when the volunteers will rehearse the experiment outside of the scanner, time for the volunteers and patients to be comfortably placed in the scanner, scanning, and finally time for the patients to slowly exit the scan room.

All MRI methods are non-invasive and no exogenous contrast agents will be required.

Patient volunteers will also undergo an C-11 PiB PET scan for Aim (2). 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.

Finally, in Aim (3) of this study, measurements of glymphatic function will be performed before and during general anesthesia. Importantly, the general anesthesia will be administered as part of standard-of-care for clinically-indicated MRIs required for deep brain stimulation planning and electrode placement. Therefore, the intervention itself is not a research procedure. Additionally, the scan that will be performed, which is a modified diffusion tensor imaging (DTI) MRI approach, is already performed as part of this clinical protocol. Therefore, it is anticipated that the participant will not be sedated any longer than what would be required for clinical indication for this procedure. As such, while this study qualifies as a clinical trial by NIH criteria, it is expected to pose no more risk than what the participant will receive from their clinical standard-of-care procedure.

Conditions

Parkinson Disease

Study Design

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

Study Groups

Parkinson's Disease participants with MCI

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.

Group Type: EXPERIMENTAL

[11C]-PIB

Intervention Type: DRUG

\[11C\]-PIB is a PET radiotracer used to evaluate levels of Αβ burden.

Interventions

[11C]-PIB

\[11C\]-PIB is a PET radiotracer used to evaluate levels of Αβ burden.

Intervention Type: DRUG

Other Intervention Names

N-Methyl-[ 11C]-2-(4'-methylaminophenyl)-6-hydroxybenzothiasole; [11C]-Pittsburgh Compound B; [ 11C]6-OH-BTA-1

Eligibility Criteria

Inclusion Criteria

• diagnosis of Parkinson's Disease or controls
• willing to participate in PET and MRI imaging

Exclusion Criteria

• recent stimulant use
• unstable diabetes
• prior stroke
• claustrophobia
• prior cancer treatment with chemotherapy
• history of traumatic brain injury
• any unstable medical condition

• Minimum Eligible Age: 55 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Vanderbilt University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Manus Donahue

Professor of Neurology, Psychiatry and Behavioral Sciences, and Radiology and Radiological Sciences

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Manus J Donahue, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Vanderbilt University Medical Center

Locations

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Countries

United States

Other Identifiers

Imaging of Brain Glymphatics

Identifier Type: -

Identifier Source: org_study_id