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

Обзор

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.

Подробное описание

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.

Вмешательства

• Устройство 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.
• Устройство 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.
• Устройство Magnetic Resonance Imaging (MRI)
  Participants will undergo 2 90-minute MRI sessions
• Устройство MAGNUS 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.

Первичные конечные точки

• Change in blood flow through the brain parenchyma - fNIRS [Срок оценки: Baseline to 4 hours]
• Change in blood flow through the brain - MRI [Срок оценки: Baseline to 90 minutes]
• Change in cerebrospinal fluid flow [Срок оценки: Baseline to 90 minutes]

Критерии участия

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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• University of Wisconsin - Madison — Madison

Идентификаторы

NCT: NCT07044596 · 2023-0970 · A535700 · Protocol Version 3/31/26 · SMPH/NEURO SURG/NEURO SURG

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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