Clinical trial NCT03622905: ADvance II Study: DBS-f in Patients With Mild Alzheimer's Disease
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Alzheimer Disease
Keywords: Mild Probable Alzheimer's Disease
Lead sponsor: Functional Neuromodulation Ltd
Sponsor class: INDUSTRY
First posted: 2018-08-09
Enrollment: 74
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility criteria: Inclusion Criteria:

1. Informed consent signed by the subject and caregiver.
2. At least 65 years old
3. Probable Alzheimer's disease according to the National Institute of Aging Alzheimer's disease Association criteria.
4. Mild dementia according to the Clinical Dementia Rating (CDR) global rating of 0.5 or 1 at screening.
5. ADAS-cog-11 score of 10-24 inclusive at screening AND baseline (with a score ≥ 4 on ADAS-cog item 1).
6. Confirmation of Alzheimer's disease based on CSF biomarkers.
7. 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.
8. Patient must be a good surgical candidate for placement of a deep brain stimulator as judged by the DBS surgical team.
9. Fluency (oral and written) in the language in which standardized tests will be administered.
10. The patient is either

    1. 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
    2. 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
    3. 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:

1. NPI total score ≥ 10 or score ≥ 4 in any NPI domain (clinically significant neuropsychiatric symptoms). Apathy score ≥ 4 acceptable.
2. Modified Hachinski ischemia scale score \> 4 at screening.
3. At risk for suicide in the opinion of the investigator or the subject answers "yes" to "Suicidal Ideation" Item 4 or 5 on the C-SSRS (at the time of evaluation) at the screening visit or attempted suicide within the last 2 years.
4. Suffers from a major psychiatric disorder such as schizophrenia, bipolar disorder or major depressive disorder, or has current alcohol or substance abuse based on psychiatric consultation at screening visit.
5. History of moderate or more severe traumatic brain injury in the 2 years prior to signing the consent to participate in the study.
6. History of brain tumor, subdural hematoma, or other clinically significant (in the judgment of the investigator) space-occupying lesion on CT or MRI.
7. History of seizure disorder.
8. 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.
9. Radiation exposure in the 1 year prior to signing the informed consent form that, in combination with the radiation exposure from this study, would exceed 5 rem.
10. Abnormal cardiovascular or neurovascular disorder that, in the opinion of the investigator would preclude participation in the study.
11. Currently prescribed or planning to start any amyloid-beta directed antibody drug (e.g. aducanumab or similar) within the first year following implantation in this study. Prior use of amyloid-beta directed antibody drugs must be stopped at least 6 months prior to signing consent.
12. Currently prescribed any non-AD medications that, in the opinion of the investigator would preclude participation in the study.
13. Is unable or unwilling to comply with protocol follow-up requirements.
14. Has a life expectancy of \< 1 year.
15. Is actively enrolled in another concurrent clinical trial.

Primary outcomes:
measure: Change From Baseline Over Time at 12 months on the Ingegrated Alzheimer's Disease Rating Scale (iADRS) [ Time Frame: From Baseline to month 12 ]
timeFrame: 12 months
Secondary outcomes:
measure: 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 ]
timeFrame: 12 months
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Barrow Neurological Institute
state: Arizona
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Stanford
country: United States
facility: Stanford University
state: California
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Saint Louis
country: United States
facility: Saint Louis University
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Health
state: North Carolina
city: Pittsburgh
country: United States
facility: Allegheny Health Network
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Austin
country: United States
facility: University of Texas
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Sciences Center at San Antonio
state: Texas
city: Toronto
country: Canada
facility: Toronto Western Hospital
state: Ontario
city: Berlin
country: Germany
facility: Universitätmedizin Charité Berlin
city: Cologne
country: Germany
facility: Universitätklinikum Köln
city: Kiel
country: Germany
facility: Universitätsklinikum Schleswig Holstein Campus
city: Magdeburg
country: Germany
facility: Universität Magdeburg
city: Munich
country: Germany
facility: Technische Universität München
city: München
country: Germany
facility: Universitätsklinikum München: Klinik und Poliklinik für Psychiatrie und Psychotherapie Alzheimer Therapie- und Forschungszentrum
city: Würzburg
country: Germany
facility: Universitätklinikum Würzburg
Study officials:
References: