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

NCT ID: NCT07044596

Last Updated: 2025-11-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

55 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-11-13

Study Completion Date

2026-08-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Mild Traumatic Brain Injury Post Concussion Syndrome

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Healthy Controls

Group Type ACTIVE_COMPARATOR

Functional near-infrared spectroscopy (fNIRS)

Intervention Type DEVICE

fNIRS is a non-invasive imaging technique which takes advantage of the light scattering and absorption differences between oxygenated (HbO) and de-oxygenated hemoglobin (HbDO) to characterize changes in cerebral hemodynamics in response to a given task or stimulus.

V1 stimulation electrodes

Intervention Type DEVICE

The V1 electrodes will be placed on the forehead with some gel and held in place with a headband or cap (a conductive adhesive gel may be placed under the electrodes to help with stimulation). Participants will receive short electrical stimulations through these electrodes that will differ in intensity.

Magnetic Resonance Imaging (MRI)

Intervention Type DEVICE

Participants will undergo 2 90-minute MRI sessions

Mild traumatic brain injury (mTBI)

Participants with recent mTBI

Group Type ACTIVE_COMPARATOR

Functional near-infrared spectroscopy (fNIRS)

Intervention Type DEVICE

fNIRS is a non-invasive imaging technique which takes advantage of the light scattering and absorption differences between oxygenated (HbO) and de-oxygenated hemoglobin (HbDO) to characterize changes in cerebral hemodynamics in response to a given task or stimulus.

V1 stimulation electrodes

Intervention Type DEVICE

The V1 electrodes will be placed on the forehead with some gel and held in place with a headband or cap (a conductive adhesive gel may be placed under the electrodes to help with stimulation). Participants will receive short electrical stimulations through these electrodes that will differ in intensity.

Magnetic Resonance Imaging (MRI)

Intervention Type DEVICE

Participants will undergo 2 90-minute MRI sessions

Interventions

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Functional near-infrared spectroscopy (fNIRS)

fNIRS is a non-invasive imaging technique which takes advantage of the light scattering and absorption differences between oxygenated (HbO) and de-oxygenated hemoglobin (HbDO) to characterize changes in cerebral hemodynamics in response to a given task or stimulus.

Intervention Type DEVICE

V1 stimulation electrodes

The V1 electrodes will be placed on the forehead with some gel and held in place with a headband or cap (a conductive adhesive gel may be placed under the electrodes to help with stimulation). Participants will receive short electrical stimulations through these electrodes that will differ in intensity.

Intervention Type DEVICE

Magnetic Resonance Imaging (MRI)

Participants will undergo 2 90-minute MRI sessions

Intervention Type DEVICE

Eligibility Criteria

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Inclusion Criteria

* 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


* 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

* Contraindication to MRI
* Known allergies to common electrode materials


* 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
Minimum Eligible Age

20 Years

Maximum Eligible Age

85 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Neuraworx Medical Technologies

UNKNOWN

Sponsor Role collaborator

University of Wisconsin, Madison

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Kip Ludwig, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Wisconsin, Madison

Locations

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University of Wisconsin - Madison

Madison, Wisconsin, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Neurosurgery Research

Role: CONTACT

608-261-1577

Other Identifiers

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A535700

Identifier Type: OTHER

Identifier Source: secondary_id

Protocol Version 3/10/25

Identifier Type: OTHER

Identifier Source: secondary_id

SMPH/NEURO SURG/NEURO SURG

Identifier Type: OTHER

Identifier Source: secondary_id

2023-0970

Identifier Type: -

Identifier Source: org_study_id

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