Cholinergic Deep Brain Stimulation for Alzheimer's Disease

Plain English Summary

Cholinergic Deep Brain Stimulation for Alzheimer's Disease is a Not Applicable clinical trial sponsored by Vanderbilt University Medical Center studying Alzheimer Disease, Early Onset, Dementia, Alzheimer Disease. This study tests if deep brain stimulation can improve thinking and memory in people with early Alzheimer's. It is for individuals recently diagnosed with early-stage Alzheimer's disease. Participation involves surgery to implant a device in the brain and daily stimulation sessions. Current treatments focus on managing symptoms; this aims to potentially modify the disease itself. The trial aims to enroll 2 participants.

Official Summary

This project will investigate the potential of Deep Brain Stimulation to improve cognitive abilities and counteract the effects of Alzheimer's disease. Deep Brain Stimulation electrodes targeting the Nucleus Basalis of Meynert (NB) will be implanted bilaterally in a cohort of patients. NB is the sole source of acetylcholine to the neocortex. Such stimulation may not only treat the cognitive symptoms but may have disease-modifying effects. Drawing from animal experiments in non-human primates that showed success of this approach, intermittent stimulation will be delivered at 60 pulses per second for 20 seconds of each minute for one hour per day. The study team will recruit patients, shortly after first being diagnosed with Alzheimer's disease. The study design will test the safety and efficacy of stimulation, potential benefits in cognitive function assessed with a battery of neurocognitive tests, cholinergic neurotransmission evaluated with Positron Emission Tomography, and ability to reverse Alzheimer's biomarkers, including beta amyloid and tau in the cerebrospinal fluid. Successful completion of this project will lead to a potential new intervention for the cognitive impairments of Alzheimer's disease.

Who Can Participate

Here is what you need to know about eligibility for this trial. You may be able to join if you have early Alzheimer's, including mild cognitive impairment, and score within a certain range on cognitive tests. You must be able to take stable doses of Alzheimer's medication and have a caregiver willing to help. You cannot join if you have other serious brain conditions, active major psychiatric disorders, or cannot undergo MRI or PET scans. This trial is studying Alzheimer Disease, Early Onset, Dementia, Alzheimer Disease, so participants generally need a confirmed diagnosis.

What They're Measuring

The primary outcome measures how a person's overall cognitive and functional abilities change over time, indicating if the stimulation helps maintain or improve daily functioning and thinking. The specific primary outcome measures are: Clinical Dementia Rating score change (12 - 24 Months). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This study does not have a traditional clinical phase designation. It may be an observational study that follows patients without intervening in their care, an expanded access or compassionate use program, or other non-interventional research. These studies contribute valuable data about disease progression, treatment patterns, and patient outcomes.

Why This Trial Matters

This trial explores a novel approach using brain stimulation to address the core memory and thinking problems in Alzheimer's, potentially offering a new way to treat the disease beyond current symptom This research targets Alzheimer Disease, Early Onset, Dementia, Alzheimer Disease, where improved treatment options are needed.

Investor Insight

This trial targets a significant unmet need in Alzheimer's treatment, with the potential for a disease-modifying therapy, representing a high-risk, high-reward investment in a large and growing market

Is This Trial Right for Me?

Ask your doctor if this experimental treatment is right for you, considering the surgical risks and daily commitment. Participation requires brain surgery to implant electrodes and daily sessions of electrical stimulation for an hour. You'll need regular visits for tests, including brain scans and cognitive assessments, and a caregiver to assist. The trial is being conducted at 1 site. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NA
• Model: SINGLE_GROUP
• Masking: NONE
• Enrollment: 2 participants

Interventions

• PROCEDURE: Device Implantation- Boston Scientific, VERCISE GENUS™ system — Participants will be implanted with DBS leads bilaterally, targeting the Nucleus Basalis of Meynert. The study team will record Local Field Potentials with and without stimulation, intraoperatively. These results will help the team determine at the end of the study whether LFP desynchronization (decrease in 5-15 Hz power), or other physiological signature, can be used to predict the location that provides the most effective intervention. Finally, the team will also ascertain the safety of the pr
• DEVICE: DBS Stimulation - Boston Scientific, VERCISE GENUS™ system — Daily intermittent stimulation (60 Hz x 20s/min)

Primary Outcomes

• Clinical Dementia Rating score change (12 - 24 Months)

Full Eligibility Criteria

Inclusion Criteria:

* Probable, early-stage AD, as defined by NIA-AA 2018 criteria, including amnestic Mild Cognitive Impairment (MCI)

  * Clinical Dementia Rating (CDR) global score of 0.5-1.0 with a memory box score of at least 0.5
  * MMSE ³ 23
  * Stable cognitive enhancer medication equivalent to 10 mg/day donepezil or less for at least 60 days
  * Stable other medications (e.g., psychotropics)
  * Valid informed consent if female, subjects who are post-menopausal or surgically sterile or willing to use birth control methods for the duration of the study
  * an available caregiver willing to participate
  * subject is living at home and likely to remain at home for the study duration.

Exclusion Criteria:

* Active or unstable psychiatric illness
* Inability to tolerate general anesthesia.
* Another concurrent CNS condition or clinical co-morbidity interfering with the study (ie, stroke, Parkinson's disease, Lewy-Body dementia or other form of dementia, other evidence of significant structural brain pathology).
* Current major psychiatric disorder such as schizophrenia, bipolar disorder or major depressive disorder based on psychiatric consult at screening visit
* Verbal IQ\<85
* Contraindication regarding anesthesia, stereotactic operation, MRI (e.g. claustrophobia, or implants), or PET (e.g. insulin dependent diabetes) procedures
* Inability to undergo PET or MRI imaging
* Active alcohol or substance abuse as defined by DSM5
* Is unable or unwilling to comply with protocol follow-up requirements
* Is actively enrolled in another concurrent clinical trial.
* Terminal illness associated with expected survival of \<12 months

Trial Locations

• Vanderbilt Medical Center, Nashville, Tennessee, United States

Frequently Asked Questions

Related Conditions

• Alzheimer Disease, Early Onset
• Dementia
• Alzheimer Disease
• Mild Cognitive Impairment
• Neurodegenerative Diseases
• Cognitive Impairment
• Memory Disorders
• Geriatric Psychiatry
• Neurology
• Brain Stimulation Therapies

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