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

NCT03622905 | Completed DMC FDA Device

• 1 other identifier: FNMI-002
• Study Type: interventional
• Target: 74
• Locations: 3 countries
• Sites: 21

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).

Conditions

Alzheimer Disease

Keywords

Mild Probable Alzheimer's Disease

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (1)

• 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 ]

  12 months

Study Arms (2)

DBS On

EXPERIMENTAL

DBS system On

Device: DBS-f On

DBS Off

SHAM COMPARATOR

DBS System Off

Device: DBS Off

Interventions

DBS-f On DEVICE

Deep Brain Stimulation of the fornix

DBS On

DBS Off DEVICE

Deep Brain Stimulation of the fornix turned off

DBS Off

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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).
• 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).

You may not qualify if:

• NPI total score ≥ 10 or score ≥ 4 in any NPI domain (clinically significant neuropsychiatric symptoms). Apathy score ≥ 4 acceptable.
• Modified Hachinski ischemia scale score \> 4 at screening.
• 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.
• 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.
• History of moderate or more severe traumatic brain injury 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.
• History of seizure disorder.
• 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.
• 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.
• Abnormal cardiovascular or neurovascular disorder that, in the opinion of the investigator would preclude participation in the study.
• 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.
• Currently prescribed any non-AD medications that, in the opinion of the investigator 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.

Sponsors & Collaborators

• Functional Neuromodulation Ltd: lead

Study Sites (21)

Barrow Neurological Institute

Phoenix, Arizona, 85013, United States

Location

University of Southern California

Los Angeles, California, 90033, United States

Location

Stanford University

Stanford, California, 94305, United States

Location

University of Florida

Gainesville, Florida, 32601, United States

Location

University of South Florida

Tampa, Florida, 33613, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21224, United States

Location

Saint Louis University

St Louis, Missouri, 63110, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68106, United States

Location

Wake Forest Baptist Health

Winston-Salem, North Carolina, 27157, United States

Location

Allegheny Health Network

Pittsburgh, Pennsylvania, 15212, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

University of Texas

Austin, Texas, 78712, United States

Location

University of Texas Health Sciences Center at San Antonio

San Antonio, Texas, 78229, United States

Location

Toronto Western Hospital

Toronto, Ontario, Canada

Location

Universitätmedizin Charité Berlin

Berlin, Germany

Location

Universitätklinikum Köln

Cologne, Germany

Location

Universitätsklinikum Schleswig Holstein Campus

Kiel, Germany

Location

Universität Magdeburg

Magdeburg, Germany

Location

Technische Universität München

Munich, Germany

Location

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

München, D-80336, Germany

Location

Universitätklinikum Würzburg

Würzburg, Germany

Location

MeSH Terms

Conditions

Alzheimer Disease

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 1, 2018
• First Posted: August 9, 2018
• Study Start: August 1, 2019
• Primary Completion: February 19, 2024
• Study Completion: February 19, 2024
• Last Updated: November 5, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

DE (7); CA (1); US (13)