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NCT Number: NCT07044596

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

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.

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Key information

Age range

20 year–85 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

University of Wisconsin - Madison

Madison, Wisconsin, 53705, United States

Location status: Recruiting

Location contact

Kip Ludwig, PhD

PRINCIPAL_INVESTIGATOR

About this study

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) stimulation. Participants with recent mild traumatic brain injuries will also be enrolled to establish feasibility within a clinically relevant population.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Functional Near-Infrared Spectroscopy (fNIRS)

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

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)

Device

Participants will undergo 2 90-minute MRI sessions

MAGNUS scanner

Device

Simultaneous Coherent-Incoherent Motion Imaging (SCIMI) available on the MAGNUS scanner will be used to perform quality control and optimization in healthy volunteers, to better resolve and visualize slow CSF flows within the brain.

Other names: GE-MAGNUS 3T MRI scanner

Primary outcomes

  1. Change in blood flow through the brain parenchyma - fNIRS

    Time frame: Baseline to 4 hours

    The fNIRS device will record changes in the blood oxygen level in the brain that is caused by the V1 stimulation.

  2. Change in blood flow through the brain - MRI

    Time frame: Baseline to 90 minutes

    The MRI will record changes in the blood oxygen level in the brain that is caused by the V1 stimulation.

  3. Change in cerebrospinal fluid flow

    Time frame: Baseline to 90 minutes

    MRI scan will be used to measure the flow of cerebrospinal fluid before, during and after stimulation.

Study contacts

Contact information is provided by the study sponsor or research team.

Neurosurgery Research

CONTACT

[email protected]

608-261-1577

Sponsors and collaborators

Lead sponsor

University of Wisconsin, Madison

Other

Collaborators

  • Neuraworx Medical Technologies

Registry information

Important dates

Study start
2025
Primary completion
2026
Study completion
2026
First posted
Jul 1, 2025
Registry last updated
May 6, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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