Cholinergic Deep Brain Stimulation for Alzheimer's Disease

April 3, 2026 updated by: Christos Constantinidis, Vanderbilt University Medical Center
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.

Study Overview

Status

Enrolling by invitation

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

2

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Deep Brain Stimulation
Patients who are implanted and receive intermittent stimulation daily for the first 12 months
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 procedure and NB stimulation itself.
Device: DBS Stimulation - Boston Scientific, VERCISE GENUS™ system
Daily intermittent stimulation (60 Hz x 20s/min)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical Dementia Rating score change
Time Frame: 12 - 24 Months
. The primary outcome indicating success will be an increase in the mean score of the Clinical Dementia Rating - Sum of Boxes of the pre-stimulation baseline that is equal or greater than the increase in the post-stimulation data by 1 point or more, after 12-36 months of stimulation.
12 - 24 Months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Vanderbilt University Medical Center

Collaborators

Boston Scientific Corporation

Investigators

  • Principal Investigator: Dave Blake, PhD, Augusta University
  • Principal Investigator: Dario Englot, MS, PhD, MD, Vanderbilt University Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

July 1, 2026

Primary Completion (Estimated)

October 1, 2028

Study Completion (Estimated)

October 1, 2028

Study Registration Dates

First Submitted

May 19, 2023

First Submitted That Met QC Criteria

May 19, 2023

First Posted (Actual)

May 31, 2023

Study Record Updates

Last Update Posted (Actual)

April 9, 2026

Last Update Submitted That Met QC Criteria

April 3, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 240675

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

This experiment will generate behavioral/cognitive assessment, imaging data, and biochemical assays under intermittent stimulation of the nucleus basalis from 2 patients. De-identified, quality-controlled raw data sets and documentation for the processed data will be made available for research purposes, in accordance with Vanderbilt IRB policy for sharing de-identified data to maximize dissemination. All data will be de-identified prior to receipt by the repository, but the information needed to generate a unique identifier (Digital Object Identifier [DOI]) will be collected for each subject. Data will be archived and shared using the Open Science Framework (OSF) repository, which is a widely accessible, open, and secure online platform for sharing scientific data and documentation. Data analysis will be performed using MATLAB and Python; these scripts will be made available on our GitHub lab website.

IPD Sharing Time Frame

Data will be made available at the time of an associated publication or at the end of the project period, whichever comes first. Unpublished data will also be made available at the end of the project period. Data will continue to be shared for a minimum of five years after the end of the project period.

IPD Sharing Access Criteria

Data will be freely available at OSF, and any research can access the data by creating a free OSF account.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • ANALYTIC_CODE
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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