Back to resultsADvance DBS-f in Patients With Mild Probable Alzheimer's Disease (ADvance)
Primary Purpose
Alzheimer Disease
Status
Completed
Phase
Not Applicable
Locations
International
Study Type
Interventional
Intervention
DBS-f on
DBS-f off
Sponsored by
About this trial
This is an interventional treatment trial for Alzheimer Disease focused on measuring Mild probable Alzheimer's Disease
Eligibility Criteria
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.
Sites / Locations
- Banner Alzheimer's Institute
- Banner Research Institute at Sun City
- University of Florida at Gainesville
- Johns Hopkins Bayview
- Hospital of the University of Pennsylvania: Penn Memory Clinic
- Brown University
- Toronto Western Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Sham Comparator
Arm Label
DBS-f on
DBS-f off
Arm Description
DBS-f on
DBS-f off
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
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.
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.
Full Information
NCT ID
NCT01608061
First Posted
May 21, 2012
Last Updated
August 21, 2020
Sponsor
Functional Neuromodulation Ltd
1. Study Identification
Unique Protocol Identification Number
NCT01608061
Brief Title
ADvance DBS-f in Patients With Mild Probable Alzheimer's Disease
Acronym
ADvance
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
August 2020
Overall Recruitment Status
Completed
Study Start Date
May 2012 (Actual)
Primary Completion Date
June 2015 (Actual)
Study Completion Date
September 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Functional Neuromodulation Ltd
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alzheimer Disease
Keywords
Mild probable Alzheimer's Disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
42 (Actual)
8. Arms, Groups, and Interventions
Arm Title
DBS-f on
Arm Type
Experimental
Arm Description
DBS-f on
Arm Title
DBS-f off
Arm Type
Sham Comparator
Arm Description
DBS-f off
Intervention Type
Device
Intervention Name(s)
DBS-f on
Other Intervention Name(s)
DBS-f system includes:, *Medtronic Activa PC Model 37601 Implantable Neurostimulator (INS), *Medtronic Model 3387 DBS Lead, *Medtronic Model 37085 DBS Extension Kit, *Medtronic Model 3708660 DBS Extension Kit
Intervention Description
deep brain stimulation of the fornix
Intervention Type
Device
Intervention Name(s)
DBS-f off
Other Intervention Name(s)
DBS-f system includes:, *Medtronic Activa PC Model 37601 Implantable Neurostimulator (INS), *Medtronic Model 3387 DBS Lead, *Medtronic Model 37085 DBS Extension Kit, *Medtronic Model 3708660 DBS Extension Kit
Intervention Description
deep brain stimulation of the fornix turned off
Primary Outcome Measure Information:
Title
Acute Safety
Description
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.
Time Frame
30 days post implant
Title
Long Term Safety. Not Based on Formal Hypotheses.
Description
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.
Time Frame
12 month
Secondary Outcome Measure Information:
Title
ADAS-Cog 13
Description
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.
Time Frame
Baseline and 12 months
Title
CDR-SB
Description
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.
Time Frame
Baseline and 12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
45 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Andres Lozano, MD, PhD
Organizational Affiliation
University Health Network, Toronto
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Constantine G Lyketsos, MD, MHS, DFAPA, FAPM
Organizational Affiliation
Johns Hopkins University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Banner Alzheimer's Institute
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85006
Country
United States
Facility Name
Banner Research Institute at Sun City
City
Sun City
State/Province
Arizona
ZIP/Postal Code
85351
Country
United States
Facility Name
University of Florida at Gainesville
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32607
Country
United States
Facility Name
Johns Hopkins Bayview
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21224
Country
United States
Facility Name
Hospital of the University of Pennsylvania: Penn Memory Clinic
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Brown University
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02906
Country
United States
Facility Name
Toronto Western Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5T 2S8
Country
Canada
12. IPD Sharing Statement
Citations:
PubMed Identifier
27567810
Citation
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.
Results Reference
derived
PubMed Identifier
26684775
Citation
Ponce 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.
Results Reference
derived
Links:
URL
http://www.advancestudy4ad.com
Description
Study Informational Website
Learn more about this trial
ADvance DBS-f in Patients With Mild Probable Alzheimer's Disease
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