CompletedNCT01608061ADvanceUpdated Aug 31, 2020Results posted

ADvance DBS-f in Patients With Mild Probable Alzheimer's Disease

An interventional study of DBS-f on and DBS-f off in Alzheimer Disease, sponsored by Functional Neuromodulation Ltd. Completed at 7 sites in 2 countries. Open to participants aged 45 Years to 85 Years. Per ClinicalTrials.gov, last updated 2020-08-31.

Sponsored by Functional Neuromodulation Ltd · Not applicable, Interventional, and Treatment

Phase: Not applicable
Study type: Interventional
Enrollment: 42
Allocation: Randomized
Ages: 45 Years to 85 Years
Sex: All

Study 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.

Conditions studied

Alzheimer Disease

Browse trials for

Alzheimer Disease 3,678

Keywords

Mild probable Alzheimer's Disease

In context

Alzheimer Disease

3,678 studies on the registry are indexed under Alzheimer Disease; 872 are open to participants now.

This study's enrollment of 42 is below the median of 70 across 2,808 interventional studies indexed under Alzheimer Disease.

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Lead sponsor

Functional Neuromodulation Ltd is the lead sponsor of 2 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 45 Years to 85 Years
Sexes eligible: All
Accepts healthy volunteers: No

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

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.

Study design

Phase: Not applicable
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment: 42 participants (actual)

Study arms

Experimental
DBS-f on
DBS-f on
Device: DBS-f on
Sham comparator
DBS-f off
DBS-f off
Device: DBS-f off

Interventions

DeviceDBS-f on
deep brain stimulation of the fornix
Also known as: 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
DeviceDBS-f off
deep brain stimulation of the fornix turned off
Also known as: 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

What researchers measure

Primary outcomes

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.
Time frame: 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.
Time frame: 12 month

Secondary outcomes

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.
Time frame: Baseline and 12 months
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.
Time frame: Baseline and 12 months

Results

Posted Aug 31, 2020

Limitations and caveats

While this feasibility trial was randomized it was not designed with formal hypotheses nor was it powered for analyses.

Participant flow

Blinded Period

Participant flow — Blinded Period
Milestone	DBS-f on	DBS-f Off
Started	21	21
Completed	21	21
Not completed	0	0

Long Term Follow-Up

Participant flow — Long Term Follow-Up
Milestone	DBS-f on	DBS-f Off
Started	21	21
Completed	14	16
Not completed	7	5

Extension Period

Participant flow — Extension Period
Milestone	DBS-f on	DBS-f Off
Started	14	16
Completed	14	14
Not completed	0	2

Outcome measures

PrimaryAcute 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.

Time frame:: 30 days post implant
Reported as:: Number · participants

Acute Safety
participants	All Implanted Subject
Acute Safety	2 (0.6 to 16.2)

PrimaryLong 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.

Time frame:: 12 month
Reported as:: Number · participants

Long Term Safety. Not Based on Formal Hypotheses.
participants	DBS-f on	DBS-f Off
Long Term Safety. Not Based on Formal Hypotheses.	0 (0 to 16.1)	1 (0.1 to 23.8)

SecondaryADAS-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.

Time frame:: Baseline and 12 months
Reported as:: Mean · score on a scale

ADAS-Cog 13
score on a scale	DBS-f on	DBS-f Off
ADAS-Cog 13	8.0 ± 2.2	8.0 ± 1.9

SecondaryCDR-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.

Time frame:: Baseline and 12 months
Reported as:: Mean · score on a scale

CDR-SB
score on a scale	DBS-f on	DBS-f Off
CDR-SB	2.5 ± 0.4	2.6 ± 0.7

Adverse events

Collected over Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
DBS-f on	1/21 (4.8%)	8/21 (38.1%)	19/21 (90.5%)
DBS-f Off	0/21 (0%)	8/21 (38.1%)	17/21 (81%)

Most frequent serious events

Showing 10 of 20

Most frequent serious events
Event	DBS-f on	DBS-f Off
SyncopeNervous system disorders	1/21	3/21
FallNervous system disorders	1/21	2/21
Device infectionInfections and infestations	2/21	1/21
UTIInfections and infestations	0/21	1/21
HeadacheGeneral disorders	1/21	0/21
Nausea and vomitingGastrointestinal disorders	1/21	0/21
SeizureNervous system disorders	1/21	0/21
Altered mental statusNervous system disorders	1/21	1/21
Skin infectionInfections and infestations	1/21	0/21
BacteremiaInfections and infestations	1/21	0/21

Most frequent other events

Showing 10 of 30

Most frequent other events
Event	DBS-f on	DBS-f Off
HeadacheGeneral disorders	6/21	7/21
ConfusionNervous system disorders	3/21	6/21
DepressionPsychiatric disorders	6/21	4/21
Respiratory InfectionInfections and infestations	5/21	4/21
FallGeneral disorders	2/21	5/21
FatigueGeneral disorders	4/21	4/21
InsomniaGeneral disorders	2/21	4/21
NauseaGeneral disorders	4/21	4/21
DiarrheaGastrointestinal disorders	2/21	3/21
EpistaxisGeneral disorders	3/21	0/21

Baseline characteristics

Age, Continuous
Age, Continuous(years)	DBS-f on	DBS-f Off	Total
Median	68.1 (51.1 to 79.7)	71.3 (48.0 to 78.0)	69.9 (48.0 to 79.7)

Sex: Female, Male
Sex: Female, Male(Participants)	DBS-f on	DBS-f Off	Total
Female	10	9	19
Male	11	12	23

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	DBS-f on	DBS-f Off	Total
Hispanic or Latino	0	2	2
Not Hispanic or Latino	21	19	40
Unknown or Not Reported	0	0	0

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	DBS-f on	DBS-f Off	Total
American Indian or Alaska Native	0	0	0
Asian	0	0	0
Native Hawaiian or Other Pacific Islander	0	0	0
Black or African American	0	0	0
White	21	20	41
More than one race	0	0	0
Unknown or Not Reported	0	1	1

ADAS-Cog 11
ADAS-Cog 11(units on a scale)	DBS-f on	DBS-f Off	Total
Median	17 (13 to 22)	17 (12 to 21)	17 (12 to 22)

CDR
CDR(Participants)	DBS-f on	DBS-f Off	Total
0.5	13	15	28
1.0	8	6	14

Study locations

7 sites

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

References and documents

Publications

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. PubMed 27567810 ↗
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. PubMed 26684775 ↗

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Aug 31, 2020, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT01608061
Lead sponsor: Functional Neuromodulation Ltd
Responsible party: Sponsor
First posted: May 30, 2012
Start date: May 2012
Primary completion: Jun 2015
Completion: Sep 2018
Results posted: Aug 31, 2020
Last update: Aug 31, 2020

Study contacts

Andres Lozano, MD, PhD

principal investigator · University Health Network, Toronto

Constantine G Lyketsos, MD, MHS, DFAPA, FAPM

principal investigator · Johns Hopkins University

Oversight

Data monitoring committee: Yes

View the source record on ClinicalTrials.gov ↗

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