Non-invasive Stimulation of the Glymphatic System for Slowing Cognitive Decline

University of Wisconsin (UW)

Status: Enrolling

Conditions: Post Concussion Syndrome; Mild Traumatic Brain Injury

Treatments: Device: V1 stimulation electrodes; Device: Functional near-infrared spectroscopy (fNIRS); Device: Magnetic Resonance Imaging (MRI)

Study type: Interventional

Funder types: Other

Identifiers

NCT07044596

SMPH/NEURO SURG/NEURO SURG (Other Identifier)

Protocol Version 3/10/25 (Other Identifier)

A535700 (Other Identifier)

2023-0970

Details and patient eligibility

About

The purpose of this research is to demonstrate that mild stimulation of a nerve (trigeminal nerve) in the head can modulate blood flow in the brain. The modulated blood flow will restore the flow of cerebrospinal fluid (CSF) and this in turn can help improve waste clearance in the brain and prevent build up that may lead to disease.

Full description

The goal of this clinical trial is to demonstrate that non-invasive stimulation of the trigeminal nerve can be used to restore blood flow and consequently modulate CSF flow into the brain parenchyma to facilitate brain waste clearance that is impaired in patients with AD. This study will collect brain MRI data on 20 healthy cognitively unimpaired adults receiving intermittent trigeminal nerve branch (V1) mouth stimulation. Participants with recent mild traumatic brain injuries will also be enrolled to establish feasibility within a clinically relevant population.

Enrollment: 55 estimated patients

Sex: All

Ages: 20 to 85 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria - Healthy Participants :

• Age 20-85 years
• Willing and able to undergo all procedures
• Free of any neurological (e.g., epilepsy, stroke, Parkinson's, brain tumors, moderate or severe traumatic brain injury), neuropsychiatric (e.g., schizophrenia, substance abuse, clinical depression), or developmental (e.g., autism, ADHD) or any other medical condition at the discretion of the PI and co-investigators

Inclusion Criteria - mTBI :

• Age 20-65
• Diagnosed with mild traumatic brain injury and be within 1-52 weeks post-injury
• Willing and able to undergo all procedures

Exclusion Criteria - Healthy Participants:

• Contraindication to MRI
• Known allergies to common electrode materials

Exclusion Criteria - mTBI:

• Contraindications for MRI
• Known allergies to common electrode materials
• Candidates currently on cardiovascular medications which, in the opinion of the investigators, would introduce a confounding factor to glymphatic system function (i.e. ACE-inhibitors, angiotensin receptor blockers, calcium channel blockers)
• Candidates who have chronic infectious diseases (e.g. hepatitis, HIV, TB)
• Candidates diagnosed with small vessel disease, vascular associated dementia (e.g. VCID), or renal disease
• Candidates retinopathies or neuropathies that, in the opinion of the investigators, would prevent them from being able to complete the study or would introduce a confounding factor to glymphatic system function
• Candidates with neurological disorders other than those attributed to their primary diagnosis (e.g. MS, PD, ALS, AD or other dementia, uncontrolled pain)
• Candidates who have had a penetrating injury, craniotomy (with the exception of a burr hole (trephination) for resolution of acute subdural hematoma), or refractory subdural hematoma
• Candidates with a history of seizures (except those in the acute or post-acute phases and are controlled)
• Candidates who experienced a loss of consciousness greater than 24 hours as a result of their TBI
• Candidates who, in the opinion of the investigators, are unable to feel a sensory referred sensation from the stimulation or successfully complete the electrode placement and testing fNIRs

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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55 participants in 2 patient groups

Healthy Controls

Active Comparator group

Treatment:

Device: Magnetic Resonance Imaging (MRI)

Device: Functional near-infrared spectroscopy (fNIRS)

Device: V1 stimulation electrodes

Mild traumatic brain injury (mTBI)

Active Comparator group

Description:

Participants with recent mTBI

Treatment:

Device: Magnetic Resonance Imaging (MRI)

Device: Functional near-infrared spectroscopy (fNIRS)

Device: V1 stimulation electrodes