ADvance II Study: DBS-f in Patients With Mild Alzheimer's Disease

NCT ID: NCT03622905

Last Updated: 2024-11-05

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

74 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-08-01

Study Completion Date

2024-02-19

Brief Summary

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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).

Detailed Description

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Conditions

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Alzheimer Disease

Keywords

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Mild Probable Alzheimer's Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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DBS On

DBS system On

Group Type EXPERIMENTAL

DBS-f On

Intervention Type DEVICE

Deep Brain Stimulation of the fornix

DBS Off

DBS System Off

Group Type SHAM_COMPARATOR

DBS Off

Intervention Type DEVICE

Deep Brain Stimulation of the fornix turned off

Interventions

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DBS-f On

Deep Brain Stimulation of the fornix

Intervention Type DEVICE

DBS Off

Deep Brain Stimulation of the fornix turned off

Intervention Type DEVICE

Eligibility Criteria

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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.
Minimum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Functional Neuromodulation Ltd

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Barrow Neurological Institute

Phoenix, Arizona, United States

Site Status

University of Southern California

Los Angeles, California, United States

Site Status

Stanford University

Stanford, California, United States

Site Status

University of Florida

Gainesville, Florida, United States

Site Status

University of South Florida

Tampa, Florida, United States

Site Status

Johns Hopkins University

Baltimore, Maryland, United States

Site Status

Saint Louis University

St Louis, Missouri, United States

Site Status

University of Nebraska Medical Center

Omaha, Nebraska, United States

Site Status

Wake Forest Baptist Health

Winston-Salem, North Carolina, United States

Site Status

Allegheny Health Network

Pittsburgh, Pennsylvania, United States

Site Status

Rhode Island Hospital

Providence, Rhode Island, United States

Site Status

University of Texas

Austin, Texas, United States

Site Status

University of Texas Health Sciences Center at San Antonio

San Antonio, Texas, United States

Site Status

Toronto Western Hospital

Toronto, Ontario, Canada

Site Status

Universitätmedizin Charité Berlin

Berlin, , Germany

Site Status

Universitätklinikum Köln

Cologne, , Germany

Site Status

Universitätsklinikum Schleswig Holstein Campus

Kiel, , Germany

Site Status

Universität Magdeburg

Magdeburg, , Germany

Site Status

Technische Universität München

Munich, , Germany

Site Status

Universitätsklinikum München: Klinik und Poliklinik für Psychiatrie und Psychotherapie Alzheimer Therapie- und Forschungszentrum

München, , Germany

Site Status

Universitätklinikum Würzburg

Würzburg, , Germany

Site Status

Countries

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United States Canada Germany

Other Identifiers

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FNMI-002

Identifier Type: -

Identifier Source: org_study_id