Mild Traumatic Brain InjuryNCT07044596
Non-invasive Stimulation of the Glymphatic System for Slowing Cognitive Decline
A study testing Functional near-infrared spectroscopy (fNIRS), V1 stimulation electrodes and Magnetic Resonance Imaging (MRI) in people with Mild Traumatic Brain Injury and Post Concussion Syndrome, run by University of Wisconsin, Madison at 1 site in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 20 to 85 yearsHealthy volunteers can take part
- Conditions the study is for
- Mild Traumatic Brain Injury, Post Concussion Syndrome
- What is being tested?
- Functional near-infrared spectroscopy (fNIRS), V1 stimulation electrodes and Magnetic Resonance Imaging (MRI)
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 55 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Nov 2025to Jun 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 85 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
Show all 13Show fewer
- 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 locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of Wisconsin - Madison
Madison, Wisconsin, 53705
Kip Ludwig, PhD
About this study
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.
Read the detailed 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) stimulation. Participants with recent mild traumatic brain injuries will also be enrolled to establish feasibility within a clinically relevant population.
- Being tested
- Functional near-infrared spectroscopy (fNIRS), V1 stimulation electrodes, Magnetic Resonance Imaging (MRI), MAGNUS scanner
- Medical subject headings
- Brain Concussion, Post-Concussion Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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 electrodesDevice
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 scannerDevice
Also called GE-MAGNUS 3T MRI scanner
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.
| Study group | Role | What they receive |
|---|---|---|
| Healthy Controls | Active comparator | Not described Receives: Device: Functional near-infrared spectroscopy (fNIRS); Device: V1 stimulation electrodes; Device: Magnetic Resonance Imaging (MRI); Device: MAGNUS scanner |
| Mild traumatic brain injury (mTBI) | Active comparator | Participants with recent mTBI Receives: Device: Functional near-infrared spectroscopy (fNIRS); Device: V1 stimulation electrodes; Device: Magnetic Resonance Imaging (MRI) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in blood flow through the brain parenchyma - fNIRS
The fNIRS device will record changes in the blood oxygen level in the brain that is caused by the V1 stimulation.
Measured: Baseline to 4 hours
Change in blood flow through the brain - MRI
The MRI will record changes in the blood oxygen level in the brain that is caused by the V1 stimulation.
Measured: Baseline to 90 minutes
Change in cerebrospinal fluid flow
MRI scan will be used to measure the flow of cerebrospinal fluid before, during and after stimulation.
Measured: Baseline to 90 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jul 2025
- Study start13 Nov 2025
- Primary completionJun 2027 (estimated)
- Study completionJun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Mild Traumatic Brain InjuryStudies of the same condition, open and under way.
- More trials run by University of Wisconsin, MadisonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 55 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Wisconsin, Madison
- Sponsor type
- University, hospital or other
- Collaborators
- Neuraworx Medical Technologies
- Responsible party
- Sponsor
- Investigators
- Kip Ludwig, PhD, Principal investigator, University of Wisconsin, Madison
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07044596
- Sponsor's protocol ID
- 2023-0970
- Other IDs
- A535700, Protocol Version 3/31/26, SMPH/NEURO SURG/NEURO SURG
- Status last verified
- Nov 2026
- First submitted
- 23 Jun 2025
- Last updated
- 4 Nov 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Non-invasive Stimulation of the Glymphatic System for Slowing Cognitive Decline
- ClinicalTrials.gov ID
- NCT07044596
- Acronym / sponsor ID
- 2023-0970
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 55 participants (estimated)
- Lead sponsor
- University of Wisconsin, MadisonUniversity, hospital or other
- Collaborators
- Neuraworx Medical Technologies
- Study start
- 13 Nov 2025 (actual)
- Primary completion
- Jun 2027 (estimated)
- Study completion
- Jun 2027 (estimated)
- First posted
- 1 Jul 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Healthy Controls | Active comparator | Device: Functional near-infrared spectroscopy (fNIRS), Device: V1 stimulation electrodes, Device: Magnetic Resonance Imaging (MRI), Device: MAGNUS scanner |
| Mild traumatic brain injury (mTBI) | Active comparator | Device: Functional near-infrared spectroscopy (fNIRS), Device: V1 stimulation electrodes, Device: Magnetic Resonance Imaging (MRI)Participants with recent mTBI |
Who may qualify
- Ages
- 20 to 85 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (13 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Device | Healthy Controls, Mild traumatic brain injury (mTBI) |
| V1 stimulation electrodesThe 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. | Device | Healthy Controls, Mild traumatic brain injury (mTBI) |
| Magnetic Resonance Imaging (MRI)Participants will undergo 2 90-minute MRI sessions | Device | Healthy Controls, Mild traumatic brain injury (mTBI) |
| MAGNUS scannerAlso: GE-MAGNUS 3T MRI scannerSimultaneous 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. | Device | Healthy Controls |
Primary outcome
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.
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.
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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2026.
- Individual participant dataSharing planned: No
Related trials for Mild Traumatic Brain Injury
Enrolling by invitationPhase 1
Pilot Safety and Exploratory Efficacy of PSC-05 for the Treatment of Chronic Mild Traumatic Brain Injury
Mild Traumatic Brain Injury
Recruiting
Evaluation of Cognitive Behavioral Therapy for Insomnia (CBT-I) in Individuals With Mild Traumatic Brain Injury (mTBI)
Sleep Architecture, Mild Traumatic Brain Injury
Recruiting
Virtual Reality in Rehabilitation of Executive Functions in Children With Mild or Moderate Traumatic Brain Injury
Traumatic Brain Injury
Active, not recruiting
Pilot TMS in Mild TBI
Persistent Post Concussive Headache, Mild Traumatic Brain Injury
Enrolling by invitation
Improving In-hospital and Post-discharge Patient Education for Mild Traumatic Brain Injury
Concussion, Mild, Traumatic Brain Injury
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Kip Ludwig, PhD principal investigator
University of Wisconsin, Madison
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Functional near-infrared spectroscopy (fNIRS), V1 stimulation electrodes and Magnetic Resonance Imaging (MRI) in people with Mild Traumatic Brain Injury and Post Concussion Syndrome, run by University of Wisconsin, Madison at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 4 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Neurosurgery Research (608-261-1577, research@neurosurgery.wisc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in blood flow through the brain parenchyma - fNIRS (time frame: Baseline to 4 hours). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Nov 2026.