Non-invasive trigeminal nerve stimulation to improve brain fluid flow and slow cognitive decline
Non-invasive Stimulation of the Glymphatic System for Slowing Cognitive Decline
This trial will try mild, non-invasive stimulation of a head nerve (the trigeminal nerve) to see if it improves cerebrospinal fluid flow and waste clearance in adults with recent mild traumatic brain injury and in healthy volunteers.
Quick facts
| Phase | Not applicable |
|---|---|
| Study type | Interventional |
| Enrollment | 55 (estimated) |
| Ages | 20 Years to 85 Years |
| Sex | All |
| Sponsor | University of Wisconsin, Madison Academic / other |
| Locations | 1 site (Madison, Wisconsin) |
| Trial ID | NCT07044596 on ClinicalTrials.gov |
What this trial studies
This interventional feasibility trial applies mild, non-invasive stimulation to the trigeminal nerve (V1) while measuring changes in cerebral blood flow and cerebrospinal fluid dynamics. Approximately 20 cognitively healthy adults and a cohort of participants 1–52 weeks after a diagnosed mild traumatic brain injury will receive intermittent V1 stimulation with simultaneous fNIRS and MRI, including sessions in the MAGNUS scanner. The study tests whether restoring blood flow via trigeminal stimulation can increase CSF influx into the brain parenchyma and facilitate clearance of metabolic waste implicated in post-concussion symptoms and neurodegenerative processes. Primary outcomes are imaging-based measures of blood and CSF flow, along with feasibility and safety signals for using this non-invasive approach in a clinical population.
Who should consider this trial
Good fit: Ideal candidates are adults able to undergo MRI and head stimulation—specifically healthy volunteers aged 20–85 and adults aged 20–65 who are 1–52 weeks post-diagnosed mild traumatic brain injury.
Not a fit: People with MRI contraindications, known allergies to electrode materials, major neurological or psychiatric disorders, or those on cardiovascular medications that would confound glymphatic function are unlikely to benefit or be eligible.
Why it matters
Potential benefit: If successful, this approach could enhance brain waste clearance and potentially reduce or slow cognitive problems after mild traumatic brain injury.
How similar studies have performed: This is an early-stage approach: animal studies and a few small human neuromodulation pilots suggest potential, but robust clinical evidence is not yet established.
Eligibility criteria
Show full inclusion / 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
Where this trial is running
Madison, Wisconsin
- University of Wisconsin - Madison — Madison, Wisconsin, United States (Recruiting)
Study contacts
- Principal investigator: Kip Ludwig, PhD — University of Wisconsin, Madison
- Study coordinator: Neurosurgery Research
- Email: research@neurosurgery.wisc.edu
- Phone: 608-261-1577
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.