Alzheimer DiseaseADvanceNCT01608061
ADvance DBS-f in Patients With Mild Probable Alzheimer's Disease
A study testing DBS-f on and DBS-f off in people with Alzheimer Disease, run by Functional Neuromodulation Ltd at 7 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 45 to 85 years
- Conditions the study is for
- Alzheimer Disease
- What is being tested?
- DBS-f on and DBS-f off
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 42 participants
- Where
- 7 sitesin 2 countries
- Study dates
- May 2012to Sep 2018
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 45 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 16Show fewer
- 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.
Trial locations and contacts
7 sites in 2 countries.
7 sites in 2 countries
United States6 sites
Johns Hopkins Bayview
Baltimore, Maryland, 21224
University of Florida at Gainesville
Gainesville, Florida, 32607
Hospital of the University of Pennsylvania: Penn Memory Clinic
Philadelphia, Pennsylvania, 19104
Banner Alzheimer's Institute
Phoenix, Arizona, 85006
Brown University
Providence, Rhode Island, 02906
Banner Research Institute at Sun City
Sun City, Arizona, 85351
About this study
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
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
- Alzheimer Disease
- Being tested
- DBS-f on, DBS-f off
- Keywords
- Mild probable Alzheimer's Disease
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DBS-f onDevice
Also called DBS-f system includes:, *Medtronic Activa PC Model 37601 Implantable Neurostimulator (INS), *Medtronic Model 3387 DBS Lead, *Medtronic Model 37085 DBS Extension Kit
deep brain stimulation of the fornix
DBS-f offDevice
Also called DBS-f system includes:, *Medtronic Activa PC Model 37601 Implantable Neurostimulator (INS), *Medtronic Model 3387 DBS Lead, *Medtronic Model 37085 DBS Extension Kit
deep brain stimulation of the fornix turned off
| Study group | Role | What they receive |
|---|---|---|
| DBS-f on | Experimental | DBS-f on Receives: Device: DBS-f on |
| DBS-f off | Sham comparator | DBS-f off Receives: Device: DBS-f off |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 12 month
Secondary outcomes (2)
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.
Measured: 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.
Measured: Baseline and 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 May 2012 (estimated)
- Study startMay 2012
- Primary completionJun 2015
- Study completionSep 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Alzheimer DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- Functional Neuromodulation Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Andres Lozano, MD, PhD, Principal investigator, University Health Network, TorontoConstantine G Lyketsos, MD, MHS, DFAPA, FAPM, Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01608061
- Sponsor's protocol ID
- FNMI-001
- Acronym
- ADvance
- Status last verified
- Aug 2020
- First submitted
- 21 May 2012
- Last updated
- 31 Aug 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
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 27567810Ponce 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
Study at a glance
From the registry record, last updated by the sponsor on 31 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01608061
- Acronym / sponsor ID
- ADvance / FNMI-001
- Conditions
- Alzheimer Disease
- Keywords
- Mild probable Alzheimer's Disease
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 42 participants (actual)
- Lead sponsor
- Functional Neuromodulation LtdIndustry (pharma, biotech, devices)
- Study start
- May 2012 (actual)
- Primary completion
- Jun 2015 (actual)
- Study completion
- Sep 2018 (actual)
- First posted
- 30 May 2012 (estimated)
- Results
- Posted 31 Aug 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| DBS-f on | Experimental | Device: DBS-f onDBS-f on |
| DBS-f off | Sham comparator | Device: DBS-f offDBS-f off |
Who may qualify
- Ages
- 45 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (16 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DBS-f onAlso: DBS-f system includes:, *Medtronic Activa PC Model 37601 Implantable Neurostimulator (INS), *Medtronic Model 3387 DBS Lead, *Medtronic Model 37085 DBS Extension Kitdeep brain stimulation of the fornix | Device | DBS-f on |
| DBS-f offAlso: DBS-f system includes:, *Medtronic Activa PC Model 37601 Implantable Neurostimulator (INS), *Medtronic Model 3387 DBS Lead, *Medtronic Model 37085 DBS Extension Kitdeep brain stimulation of the fornix turned off | Device | DBS-f off |
Primary outcome
Acute Safety
Time frame: 30 days post implant
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.
Time frame: 12 month
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.
2 secondary outcomes
ADAS-Cog 13
Time frame: Baseline and 12 months
CDR-SB
Time frame: Baseline and 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Aug 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 27567810Lozano 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.
- Derived from this study: PubMed 26684775Ponce 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.
- Study Informational WebsiteLink provided by the sponsor.
Related trials for Alzheimer Disease
RecruitingPhase 2
Neuroplasticity Enhancement From Cognitive Training Reinforced by Psilocybin
Alzheimer's Disease
Not yet recruiting
Acupressure as Long-term Intervention to Slow the Progression of Early/Mild Alzheimer's Disease
Alzheimer's Disease
RecruitingObservational study
Effectiveness and Safety of Disease-Modifying Therapy for Alzheimer's Disease: A Multicenter Retrospective Study
Alzheimer's Disease (AD)
RecruitingPhase 3
A Phase 3 Study to Evaluate the Safety and Efficacy of KarXT + KarX-EC for the Treatment of Agitation Associated With Alzheimer's Disease (ADAGIO-1)
Alzheimer Disease
RecruitingPhase 3
A Study of Trontinemab in Cognitively Unimpaired Individuals at Risk for Progression to Symptomatic Alzheimer's Disease
Alzheimer's Disease
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Andres Lozano, MD, PhD principal investigator
University Health Network, Toronto
Constantine G Lyketsos, MD, MHS, DFAPA, FAPM principal investigator
Johns Hopkins University
7 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing DBS-f on and DBS-f off in people with Alzheimer Disease, run by Functional Neuromodulation Ltd at 7 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 31 Aug 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Acute Safety (time frame: 30 days post implant). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01608061, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Aug 2020.