Cholinergic Deep Brain Stimulation for Alzheimer's Disease

Обзор

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.

Вмешательства

• Процедура 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
• Устройство DBS Stimulation - Boston Scientific, VERCISE GENUS™ system
  Daily intermittent stimulation (60 Hz x 20s/min)

Первичные конечные точки

• Clinical Dementia Rating score change [Срок оценки: 12 - 24 Months]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• Vanderbilt Medical Center — Nashville

Публикации

• 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. PMID 34392372
• 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 2 PMID 24798585
• 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. Alzhei PMID 21514250
• 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. PMID 8232972
• 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. PMID 23653484
• 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. PMID 36449413
• 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. PMID 22858530

Идентификаторы

NCT: NCT05882344 · 240675

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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