Alzheimer Disease, Early OnsetNCT05882344
Cholinergic Deep Brain Stimulation for Alzheimer's Disease
A study testing Device Implantation- Boston Scientific, VERCISE GENUS™ system and DBS Stimulation - Boston Scientific, VERCISE GENUS™ system in people with Alzheimer Disease, Early Onset and Dementia, run by Vanderbilt University Medical Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 60 to 80 years
- Conditions the study is for
- Alzheimer Disease, Early Onset, Dementia, Alzheimer Disease
- What is being tested?
- Device Implantation- Boston Scientific, VERCISE GENUS™ system and DBS Stimulation - Boston Scientific, VERCISE GENUS™ system
- Type of treatment
- Medical device, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2026to Oct 2028
- Phase
- Interventional
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 60 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
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- 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 and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site
Vanderbilt Medical Center
Nashville, Tennessee, 37232
About this study
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.
- Conditions
- Alzheimer Disease, Early Onset, Dementia, Alzheimer Disease
- Being tested
- Device Implantation- Boston Scientific, VERCISE GENUS™ system, DBS Stimulation - Boston Scientific, VERCISE GENUS™ system
- Keywords
- Stimulation, Nucleus Basalis, Alzheimer, Memory
- Medical subject headings
- Alzheimer Disease, Dementia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Device Implantation- Boston Scientific, VERCISE GENUS™ systemProcedure or surgery
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™ systemDevice
Daily intermittent stimulation (60 Hz x 20s/min)
| Study group | Role | What they receive |
|---|---|---|
| Deep Brain Stimulation | Experimental | Patients who are implanted and receive intermittent stimulation daily for the first 12 months Receives: Procedure: Device Implantation- Boston Scientific, VERCISE GENUS™ system; Device: DBS Stimulation - Boston Scientific, VERCISE GENUS™ system |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical Dementia Rating score change
. 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.
Measured: 12 - 24 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 May 2023
- Study startNov 2026 (estimated)
- Primary completionOct 2028 (estimated)
- Study completionOct 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Alzheimer Disease, Early OnsetStudies of the same condition, open and under way.
- More trials run by Vanderbilt University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 2 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Vanderbilt University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Boston Scientific Corporation
- Responsible party
- Principal investigator, Christos Constantinidis, Vanderbilt University Medical Center
- Investigators
- Dave Blake, PhD, Principal investigator, Augusta UniversityDario Englot, MS, PhD, MD, Principal investigator, Vanderbilt University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05882344
- Sponsor's protocol ID
- 240675
- Status last verified
- Apr 2026
- First submitted
- 19 May 2023
- Last updated
- 1 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Yes: 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.
Publications
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.
PubMed 34392372Kuhn 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.
PubMed 24798585McKhann 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.
PubMed 21514250Morris 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.
PubMed 8232972Todd 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.
PubMed 23653484van 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.
PubMed 36449413Williams 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.
PubMed 22858530