ADvance DBS-f in Patients With Mild Probable Alzheimer's Disease

Study Overview
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Brief Summary
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The primary objective of this feasibility study is to evaluate the safety of DBS-f in patients with mild Alzheimer's disease by assessing all device and/or therapy related adverse events. The secondary objective is to preliminarily estimate the treatment effect size on the outcomes of interest at 12 months post-randomization. The objectives do not involve formal tests of hypotheses.

Official Title
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A Twelve Month Double-blind Randomized Controlled Feasibility Study to Evaluate the Safety, Efficacy and Tolerability of Deep Brain Stimulation of the Fornix (DBS-f) in Patients With Mild Probable Alzheimer's Disease

Conditions
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Alzheimer Disease

Intervention / Treatment
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* Device: DBS-f on
* Device: DBS-f off


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 45-85 years of age (inclusive) Probable Alzheimer's disease according to the National Institute of Aging Alzheimer's disease Association criteria. Must meet certain criteria on cognitive and behavioral rating scales 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. The subject is currently taking a stable dose of cholinesterase inhibitor (AChEI) medication for at least 60 days Exclusion Criteria: Must meet certain criteria on cognitive and behavioral rating scales Current major psychiatric disorder such as schizophrenia, bipolar disorder or major depressive disorder based on psychiatric consult at screening visit History of head trauma in the 2 years prior to signing the consent to participate in the study History of brain tumor, subdural hematoma, or other clinically significant (in the judgment of the investigator) space-occupying lesion on CT or MRI Active psychiatric disorder Mental retardation Current alcohol or substance abuse as defined by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) Contraindications for PET scanning (e.g., insulin dependent diabetes) Contraindications for MRI scanning, including implanted metallic devices (e.g. non-MRI-safe cardiac pacemaker or neurostimulator; some artificial joints metal pins; surgical clips; or other implanted metal parts), or claustrophobia or discomfort in confined spaces. Abnormal lab results that, in the opinion of the investigator and/or enrollment review committee, would preclude participation in the study. Abnormal cardiovascular or neurovascular disorder that, in the opinion of the investigator and/or enrollment review committee, would preclude participation in the study. Unstable doses of any medication prescribed for the treatment of memory loss or Alzheimer's disease. Currently prescribed any non-AD medications that, in the opinion of the investigator and/or enrollment review committee, would preclude participation in the study. Is unable or unwilling to comply with protocol follow-up requirements. Has a life expectancy of < 1 year. Is actively enrolled in another concurrent clinical trial.

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DBS-f on<br>DBS-f on | Device: DBS-f on<br>* deep brain stimulation of the fornix<br>* Other names: *Medtronic Model 3708660 DBS Extension Kit;|
| Sham Comparator: DBS-f off<br>DBS-f off | Device: DBS-f off<br>* deep brain stimulation of the fornix turned off<br>* Other names: *Medtronic Model 3708660 DBS Extension Kit;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute Safety | Acute safety will be assessed by estimating the rate of serious device (pulse generator or lead) or procedure related adverse events from the date of implant through the date of randomization, plus serious procedure related events through 30 days post-implant. All subjects undergoing an implant procedure will be included in these rate estimates. The rate and 95% confidence interval will be presented. Analysis is of a timepoint prior to randomization and thus all subjects are analyzed together. | 30 days post implant | 
| Long Term Safety. Not Based on Formal Hypotheses. | Long-term safety will be assessed by the rate of serious device or therapy related adverse events from the date of randomization through the date of the Month 12 visit. The rate and 95% confidence interval will be presented by randomization group. All subjects randomized will be included. | 12 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ADAS-Cog 13 | The mean change from baseline (pre-implant) to 12 months will be calculated in each treatment group. The differences between randomized groups in mean change will be calculated, along with corresponding 2-sided, 95% confidence intervals. Instrument is Alzheimer's Disease Assessment Scale - Cognitive subscale. Scores range from 0 to 85 with higher scores meaning worse outcome. | Baseline and 12 months | 
| CDR-SB | The mean change from baseline (pre-implant) to 12 months will be calculated in each treatment group. The differences between randomized groups in mean change will be calculated, along with corresponding 2-sided, 95% confidence intervals. The scale used is the Clinical Dementia Rating Scale and the score used is the sum of boxes. The scores for this measure range from 0 to 18 with a higher score indicating a worse outcome. | Baseline and 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mild probable Alzheimer's Disease