ADvance DBS-f in Patients With Mild Probable Alzheimer's Disease
ADvance
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
1 other identifier
interventional
42
2 countries
7
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for not_applicable alzheimer-disease
Started May 2012
Longer than P75 for not_applicable alzheimer-disease
7 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
May 1, 2012
CompletedFirst Submitted
Initial submission to the registry
May 21, 2012
CompletedFirst Posted
Study publicly available on registry
May 30, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 1, 2015
CompletedStudy Completion
Last participant's last visit for all outcomes
September 1, 2018
CompletedResults Posted
Study results publicly available
August 31, 2020
CompletedAugust 31, 2020
August 1, 2020
3.1 years
May 21, 2012
February 18, 2020
August 21, 2020
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
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 Outcomes (2)
ADAS-Cog 13
Baseline and 12 months
CDR-SB
Baseline and 12 months
Study Arms (2)
DBS-f on
EXPERIMENTALDBS-f on
DBS-f off
SHAM COMPARATORDBS-f off
Interventions
deep brain stimulation of the fornix
deep brain stimulation of the fornix turned off
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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.
- +1 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (7)
Banner Alzheimer's Institute
Phoenix, Arizona, 85006, United States
Banner Research Institute at Sun City
Sun City, Arizona, 85351, United States
University of Florida at Gainesville
Gainesville, Florida, 32607, United States
Johns Hopkins Bayview
Baltimore, Maryland, 21224, United States
Hospital of the University of Pennsylvania: Penn Memory Clinic
Philadelphia, Pennsylvania, 19104, United States
Brown University
Providence, Rhode Island, 02906, United States
Toronto Western Hospital
Toronto, Ontario, M5T 2S8, Canada
Related Publications (2)
Lozano AM, Fosdick L, Chakravarty MM, Leoutsakos JM, Munro C, Oh E, Drake KE, Lyman CH, Rosenberg PB, Anderson WS, Tang-Wai DF, Pendergrass JC, Salloway S, Asaad WF, Ponce FA, Burke A, Sabbagh M, Wolk DA, Baltuch G, Okun MS, Foote KD, McAndrews MP, Giacobbe P, Targum SD, Lyketsos CG, Smith GS. A Phase II Study of Fornix Deep Brain Stimulation in Mild Alzheimer's Disease. J Alzheimers Dis. 2016 Sep 6;54(2):777-87. doi: 10.3233/JAD-160017.
PMID: 27567810DERIVEDPonce FA, Asaad WF, Foote KD, Anderson WS, Rees Cosgrove G, Baltuch GH, Beasley K, Reymers DE, Oh ES, Targum SD, Smith GS, Lyketsos CG, Lozano AM; ADvance Research Group. Bilateral deep brain stimulation of the fornix for Alzheimer's disease: surgical safety in the ADvance trial. J Neurosurg. 2016 Jul;125(1):75-84. doi: 10.3171/2015.6.JNS15716. Epub 2015 Dec 18.
PMID: 26684775DERIVED
Related Links
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Limitations and Caveats
While this feasibility trial was randomized it was not designed with formal hypotheses nor was it powered for analyses.
Results Point of Contact
- Title
- Todd Langevin
- Organization
- Functional Neuromodulation
Study Officials
- PRINCIPAL INVESTIGATOR
Andres Lozano, MD, PhD
University Health Network, Toronto
- PRINCIPAL INVESTIGATOR
Constantine G Lyketsos, MD, MHS, DFAPA, FAPM
Johns Hopkins University
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
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
May 21, 2012
First Posted
May 30, 2012
Study Start
May 1, 2012
Primary Completion
June 1, 2015
Study Completion
September 1, 2018
Last Updated
August 31, 2020
Results First Posted
August 31, 2020
Record last verified: 2020-08