Deep Brain Stimulation for Alzheimer's

Alzheimer Disease Clinical Trial

Official title:

Cholinergic Deep Brain Stimulation for Alzheimer's Disease

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05882344
• Other study ID #: 221713
• Status: Not yet recruiting
• Phase: N/A
• Start date: February 1, 2025
• Est. completion date: October 2028

Study information

• Verified date: February 2024
• Source: Vanderbilt University Medical Center
• Contact: Chrissy Suell
• Phone: 615-875-8056
• Email: chrissy.suell[@]vanderbilt.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 8
• Est. completion date: October 2028
• Est. primary completion date: October 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer Disease, Early Onset
• Dementia

Intervention

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)

Locations

Country	Name	City	State
United States	Vanderbilt Medical Center	Nashville	Tennessee

Sponsors (2)

Lead Sponsor	Collaborator
Vanderbilt University Medical Center	Boston Scientific Corporation

Country where clinical trial is conducted

United States, 

References & Publications (7)

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 (Hagerstown). 2021 Oct 13;21(5):277-290. doi: 10.1093/ons/opab261. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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 sham group relative to its baseline that is equal or greater than the increase in the mean score of the NB stimulation group (relative to its own baseline) by 1 point or more	12 - 24 Months