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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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| DBS On | Experimental | DBS system On |
|
| DBS Off | Sham Comparator | DBS System Off |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| DBS-f On | Device | Deep Brain Stimulation of the fornix |
| |
| DBS Off |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline Over Time at 12 months on the Ingegrated Alzheimer's Disease Rating Scale (iADRS) [ Time Frame: From Baseline to month 12 ] | The iADRS is a composite tool that combines scores from the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) and the Alzheimer's Disease Cooperative Study - instrumental Activities of Daily Living (ADCS-iADL). It measures both cognition and function and demonstrates acceptable psychometric properties, and is effective in capturing both disease progression and separation of placebo and active treatment effect. The iADRS score ranges from 0 to 146 with lower scores indicating worse performance. | 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline Over Time at 12 months on the Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) [ Time Frame: From Baseline to month 12 ] | The CDR-SB is a validated clinical assessment of global function in patients with AD. Impairment is scored in each of 6 cognitive categories on a scale in which none = 0, questionable = 0.5, mild = 1, moderate = 2, and severe = 3. The 6 individual category ratings, or "box scores", can be added together to give the CDR-SB which ranges from 0 to 18 (severe impairment). |
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Inclusion Criteria:
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).
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Barrow Neurological Institute | Phoenix | Arizona | 85013 | United States | ||
| University of Southern California |
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| Device |
Deep Brain Stimulation of the fornix turned off |
|
| 12 months |
| Los Angeles |
| California |
| 90033 |
| United States |
| Stanford University | Stanford | California | 94305 | United States |
| University of Florida | Gainesville | Florida | 32601 | United States |
| University of South Florida | Tampa | Florida | 33613 | United States |
| Johns Hopkins University | Baltimore | Maryland | 21224 | United States |
| Saint Louis University | St Louis | Missouri | 63110 | United States |
| University of Nebraska Medical Center | Omaha | Nebraska | 68106 | United States |
| Wake Forest Baptist Health | Winston-Salem | North Carolina | 27157 | United States |
| Allegheny Health Network | Pittsburgh | Pennsylvania | 15212 | United States |
| Rhode Island Hospital | Providence | Rhode Island | 02903 | United States |
| University of Texas | Austin | Texas | 78712 | United States |
| University of Texas Health Sciences Center at San Antonio | San Antonio | Texas | 78229 | United States |
| Toronto Western Hospital | Toronto | Ontario | Canada |
| Universitätmedizin Charité Berlin | Berlin | Germany |
| Universitätklinikum Köln | Cologne | Germany |
| Universitätsklinikum Schleswig Holstein Campus | Kiel | Germany |
| Universität Magdeburg | Magdeburg | Germany |
| Technische Universität München | Munich | Germany |
| Universitätsklinikum München: Klinik und Poliklinik für Psychiatrie und Psychotherapie Alzheimer Therapie- und Forschungszentrum | München | D-80336 | Germany |
| Universitätklinikum Würzburg | Würzburg | Germany |
| ID | Term |
|---|---|
| D000544 | Alzheimer Disease |
| ID | Term |
|---|---|
| D003704 | Dementia |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D024801 | Tauopathies |
| D019636 | Neurodegenerative Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
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