Cholinergic Deep Brain Stimulation for Alzheimer's Disease

NCT ID: NCT05882344

Last Updated: 2025-12-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

NA

Total Enrollment

2 participants

Study Classification

INTERVENTIONAL

Study Start Date

2026-06-01

Study Completion Date

2028-10-31

Brief Summary

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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.

Detailed Description

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Conditions

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Alzheimer Disease, Early Onset Dementia Alzheimer Disease

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

This is a feasibility study to 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 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. Intermittent stimulation will be delivered at 60 pulses per second for 20 seconds of each minute for one hour per day. The study design will test the safety and feasibility 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.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Deep Brain Stimulation

Patients who are implanted and receive intermittent stimulation daily for the first 12 months

Group Type EXPERIMENTAL

Device Implantation- Boston Scientific, VERCISE GENUS™ system

Intervention Type PROCEDURE

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.

DBS Stimulation - Boston Scientific, VERCISE GENUS™ system

Intervention Type DEVICE

Daily intermittent stimulation (60 Hz x 20s/min)

Interventions

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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.

Intervention Type PROCEDURE

DBS Stimulation - Boston Scientific, VERCISE GENUS™ system

Daily intermittent stimulation (60 Hz x 20s/min)

Intervention Type DEVICE

Eligibility Criteria

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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
Minimum Eligible Age

60 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Boston Scientific Corporation

INDUSTRY

Sponsor Role collaborator

Vanderbilt University Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Christos Constantinidis

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Dave Blake, PhD

Role: PRINCIPAL_INVESTIGATOR

Augusta University

Dario Englot, MS, PhD, MD

Role: PRINCIPAL_INVESTIGATOR

Vanderbilt University Medical Center

Locations

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Vanderbilt Medical Center

Nashville, Tennessee, United States

Site Status

Countries

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United States

Central Contacts

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Kristin Clifft

Role: CONTACT

615-875-8056

Facility Contacts

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Kristin Clifft

Role: primary

6158758056

References

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Koh EJ, Golubovsky JL, Rammo R, Momin A, Walter B, Fernandez HH, Machado A, Nagel SJ. Estimating the Risk of Deep Brain Stimulation in the Modern Era: 2008 to 2020. Oper Neurosurg. 2021 Oct 13;21(5):277-290. doi: 10.1093/ons/opab261.

Reference Type BACKGROUND
PMID: 34392372 (View on PubMed)

Kuhn J, Hardenacke K, Lenartz D, Gruendler T, Ullsperger M, Bartsch C, Mai JK, Zilles K, Bauer A, Matusch A, Schulz RJ, Noreik M, Buhrle CP, Maintz D, Woopen C, Haussermann P, Hellmich M, Klosterkotter J, Wiltfang J, Maarouf M, Freund HJ, Sturm V. Deep brain stimulation of the nucleus basalis of Meynert in Alzheimer's dementia. Mol Psychiatry. 2015 Mar;20(3):353-60. doi: 10.1038/mp.2014.32. Epub 2014 May 6.

Reference Type BACKGROUND
PMID: 24798585 (View on PubMed)

McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR Jr, Kawas CH, Klunk WE, Koroshetz WJ, Manly JJ, Mayeux R, Mohs RC, Morris JC, Rossor MN, Scheltens P, Carrillo MC, Thies B, Weintraub S, Phelps CH. The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011 May;7(3):263-9. doi: 10.1016/j.jalz.2011.03.005. Epub 2011 Apr 21.

Reference Type BACKGROUND
PMID: 21514250 (View on PubMed)

Morris JC. The Clinical Dementia Rating (CDR): current version and scoring rules. Neurology. 1993 Nov;43(11):2412-4. doi: 10.1212/wnl.43.11.2412-a. No abstract available.

Reference Type BACKGROUND
PMID: 8232972 (View on PubMed)

Todd S, Barr S, Passmore AP. Cause of death in Alzheimer's disease: a cohort study. QJM. 2013 Aug;106(8):747-53. doi: 10.1093/qjmed/hct103. Epub 2013 May 7.

Reference Type BACKGROUND
PMID: 23653484 (View on PubMed)

van Dyck CH, Swanson CJ, Aisen P, Bateman RJ, Chen C, Gee M, Kanekiyo M, Li D, Reyderman L, Cohen S, Froelich L, Katayama S, Sabbagh M, Vellas B, Watson D, Dhadda S, Irizarry M, Kramer LD, Iwatsubo T. Lecanemab in Early Alzheimer's Disease. N Engl J Med. 2023 Jan 5;388(1):9-21. doi: 10.1056/NEJMoa2212948. Epub 2022 Nov 29.

Reference Type BACKGROUND
PMID: 36449413 (View on PubMed)

Williams MM, Storandt M, Roe CM, Morris JC. Progression of Alzheimer's disease as measured by Clinical Dementia Rating Sum of Boxes scores. Alzheimers Dement. 2013 Feb;9(1 Suppl):S39-44. doi: 10.1016/j.jalz.2012.01.005. Epub 2012 Aug 1.

Reference Type BACKGROUND
PMID: 22858530 (View on PubMed)

Other Identifiers

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240675

Identifier Type: -

Identifier Source: org_study_id