ADvance II: A 12-month Double-blind, Randomized, Controlled Study to Evaluate the Safety and Efficacy of Deep Brain Stimulation of the Fornix (DBS-f) in Patients With Mild Probable Alzheimer's Disease
The primary efficacy objective of this study is to test the hypothesis that DBS-f stimulation (ON) will slow cognitive and functional progression of AD, as compared to no stimulation (OFF), by measuring baseline (pre-implantation) to 12-month change in the integrated Alzheimer's disease rating scale (iADRS).
• Informed consent signed by the subject and caregiver.
• At least 65 years old
• Probable Alzheimer's disease according to the National Institute of Aging Alzheimer's disease Association criteria.
• Mild dementia according to the Clinical Dementia Rating (CDR) global rating of 0.5 or 1 at screening.
• ADAS-cog-11 score of 10-24 inclusive at screening AND baseline (with a score ≥ 4 on ADAS-cog item 1).
• Confirmation of Alzheimer's disease based on CSF biomarkers.
• The patient has an available caregiver or other appropriate knowledgeable informant who can reliably report on daily activities and function and signs the informed consent for participation as such.
• Patient must be a good surgical candidate for placement of a deep brain stimulator as judged by the DBS surgical team.
• Fluency (oral and written) in the language in which standardized tests will be administered.
⁃ The patient is either
∙ taking a stable dose of cholinesterase inhibitor (AChEI) medication (donepezil, galantamine, or rivastigmine) for at least 60 days prior to signing the informed consent form OR
‣ the patient has previously had an intolerance/failure to cholinesterase inhibitor medications that can be documented AND there is no intention to modify the dose over the course of the study (NOTE: These medications may NOT be initiated, discontinued or modified during the 12-month control period).
∙ OR
‣ c) a physician has fully discussed the possibility of prescribing cholinesterase inhibitors and the physician in collaboration with the patient/caregiver have declined trying cholinesterase inhibitors and this discussion and decision are fully documented in the patient's medical records. This discussion occurred during the course of the patient's care, and not as a component of enrollment or discussion of participation in this clinical trial.
• AND there is no intention to modify the dose over the course of the study (NOTE: These medications may NOT be initiated, discontinued or modified after study initiation for the 12-months control period).