Non-invasive Stimulation for Cognitive Decline

Overseen By Neurosurgery Research

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Wisconsin, Madison

Must not be taking: Cardiovascular medications

Disqualifiers: Chronic infectious diseases, Small vessel disease, Renal disease, Neurological disorders, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 1 day

55 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if gentle stimulation of a nerve in the head can improve blood flow in the brain. Improved blood flow may help clear waste from the brain, potentially preventing diseases linked to cognitive decline. The trial includes individuals with a recent mild traumatic brain injury (mTBI) or those who are healthy. Participants should not have major neurological or psychiatric conditions and must be able to undergo all procedures. As an unphased trial, this study offers participants the chance to contribute to groundbreaking research that could lead to new methods for preventing cognitive decline.

Will I have to stop taking my current medications?

If you are currently on cardiovascular medications like ACE-inhibitors, angiotensin receptor blockers, or calcium channel blockers, you may need to stop taking them to participate in the trial, as they could affect the study results.

What prior data suggests that this non-invasive stimulation is safe for cognitive decline?

Research has shown that non-invasive stimulation of the trigeminal nerve has been studied in people. This treatment aims to help the brain clear waste and improve blood flow. Although direct information on its safety is limited, non-invasive procedures typically pose fewer risks than surgery.

For similar treatments, studies have found they are often well-tolerated with few side effects. Non-invasive methods like this are designed to be safe, especially in early testing stages. If this treatment were already approved for another condition, it would likely have a stronger safety record, but it's unclear if that's the case here.

Overall, even without detailed safety data for this specific treatment, non-invasive approaches generally aim to reduce the chance of negative effects. This can reassure those considering joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about non-invasive stimulation of the glymphatic system because it offers a fresh approach to addressing cognitive decline, particularly following mild traumatic brain injuries (mTBI). Unlike traditional treatments that may focus on medication or cognitive therapy, this technique targets the brain's natural waste clearance system, potentially enhancing brain health and function without the need for drugs. The non-invasive nature of the treatment means it's less risky and more accessible, making it a promising alternative to existing options. Additionally, by improving the glymphatic system's efficiency, this method could offer quicker and more direct results in mitigating cognitive issues.

What evidence suggests that non-invasive stimulation of the glymphatic system is effective for cognitive decline?

This trial will investigate non-invasive stimulation of the glymphatic system, which research has shown can improve brain function by affecting blood flow. This process connects to the glymphatic system, which clears waste from the brain. Studies suggest that issues with this system might link to cognitive problems after mild brain injuries. By enhancing the glymphatic system's function, non-invasive stimulation might alleviate these symptoms. Early findings indicate that this stimulation could support better brain health, especially for individuals with mild traumatic brain injuries. Participants in this trial will include those with recent mild traumatic brain injuries and healthy controls. ^{1 2 3 4 6}

Who Is on the Research Team?

Kip Ludwig, PhD

Principal Investigator

University of Wisconsin, Madison

Are You a Good Fit for This Trial?

This trial is for adults aged 20-65 with mild traumatic brain injury (mTBI) within a year of injury, and healthy individuals aged 20-85. Participants must be able to undergo all procedures without MRI contraindications or allergies to electrode materials. Those on certain cardiovascular meds, with chronic diseases, neurological disorders other than mTBI, history of severe head trauma or seizures cannot join.

Inclusion Criteria

Healthy Participants: Willing and able to undergo all procedures

Healthy Participants: Free of any neurological, neuropsychiatric, developmental, or any other medical condition at the discretion of the PI and co-investigators

mTBI: Willing and able to undergo all procedures

Exclusion Criteria

Healthy Participants: Contraindication to MRI

Healthy Participants: Known allergies to common electrode materials

mTBI: Known allergies to common electrode materials

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intermittent trigeminal nerve branch (V1) mouth stimulation

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Non-invasive Stimulation of the Glymphatic System

Trial Overview The study tests if stimulating the trigeminal nerve non-invasively can improve blood flow in the brain using devices like fNIRS and V1 electrodes. This could enhance waste clearance from the brain. Participants will also have MRIs to monitor changes.

How Is the Trial Designed?

Group I: Mild traumatic brain injury (mTBI) Active Control 3 Interventions

Participants with recent mTBI

Group II: Healthy Controls Active Control 3 Interventions

Who Is Running the Clinical Trial?

University of Wisconsin, Madison

Lead Sponsor

Trials

1,249

Recruited

3,255,000+

Neuraworx Medical Technologies

Collaborator

Citations

1. go.drugbank.com go.drugbank.com/conditions/DBCOND0068001

Mild Traumatic Brain Injury (MTBI) (DBCOND0068001) Non-invasive Stimulation of the Glymphatic System for Slowing Cognitive Decline, No drug interventions, treatment, Not Available, recruiting. NCT06551987.

2. frontiersin.org frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2025.1597311/full

The glymphatic system as a therapeutic target These results provide novel evidence that TBS can modulate glymphatic function in humans and raise interesting questions about the relevance of APOE status.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT07044596

Non-invasive Stimulation of the Glymphatic System for ... This study will collect brain MRI data on 20 healthy cognitively unimpaired adults receiving intermittent trigeminal nerve branch (V1) mouth stimulation.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12572939/

Glymphatic system and mild traumatic brain injury Notably, sleep deprivation, post-concussive symptoms, and cognitive impairment have often been linked to post-injury glymphatic dysfunction.

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/41179995/

Glymphatic system and mild traumatic brain injury Notably, sleep deprivation, post-concussive symptoms, and cognitive impairment have often been linked to post-injury glymphatic dysfunction.

6. frontiersin.org frontiersin.org/journals/neurology/articles/10.3389/fneur.2025.1560777/full

Non-invasive therapeutics for neurotrauma: a mechanistic ... Here we review the current literature of non-invasive therapies in preclinical neurotrauma and offer insight into the potential mechanism of action and novel ...