Alzheimer DiseaseNCT03622905
ADvance II Study: DBS-f in Patients With Mild Alzheimer's Disease
A study testing DBS-f On and DBS Off in people with Alzheimer Disease, run by Functional Neuromodulation Ltd at 21 sites in 3 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 65 years and older
- Conditions the study is for
- Alzheimer Disease
- What is being tested?
- DBS-f On and DBS Off
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 74 participants
- Where
- 21 sitesin 3 countries
- Study dates
- 1 Aug 2019to 19 Feb 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 65 years and older
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- 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.
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- 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).
- OR
- 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).
Who cannot join
- 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.
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- 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.
Trial locations and contacts
21 sites in 3 countries.
21 sites in 3 countries
United States13 sites
University of Texas
Austin, Texas, 78712
Johns Hopkins University
Baltimore, Maryland, 21224
University of Florida
Gainesville, Florida, 32601
University of Southern California
Los Angeles, California, 90033
University of Nebraska Medical Center
Omaha, Nebraska, 68106
Barrow Neurological Institute
Phoenix, Arizona, 85013
Allegheny Health Network
Pittsburgh, Pennsylvania, 15212
Rhode Island Hospital
Providence, Rhode Island, 02903
University of Texas Health Sciences Center at San Antonio
San Antonio, Texas, 78229
Saint Louis University
St Louis, Missouri, 63110
Stanford University
Stanford, California, 94305
University of South Florida
Tampa, Florida, 33613
Wake Forest Baptist Health
Winston-Salem, North Carolina, 27157
Germany7 sites
Universitätmedizin Charité Berlin
Berlin
Universitätklinikum Köln
Cologne
Universitätsklinikum Schleswig Holstein Campus
Kiel
Universität Magdeburg
Magdeburg
Universitätsklinikum München: Klinik und Poliklinik für Psychiatrie und Psychotherapie Alzheimer Therapie- und Forschungszentrum
München, D-80336
Technische Universität München
Munich
Universitätklinikum Würzburg
Würzburg
About this study
Official title: ADvance II: A 12-month Double-blind, Randomized, Controlled Study to Evaluate the Safety and Efficacy of Deep Brain Stimulation of the Fornix (DBS-f) in Patients With Mild Probable Alzheimer's Disease
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
- Being tested
- DBS-f On, DBS 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
Deep Brain Stimulation of the fornix
DBS OffDevice
Deep Brain Stimulation of the fornix turned off
| Study group | Role | What they receive |
|---|---|---|
| DBS On | Experimental | DBS system On Receives: Device: DBS-f On |
| DBS Off | Sham comparator | DBS System Off Receives: Device: DBS Off |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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 ]
The CDR-SB is a validated clinical assessment of global function in patients with AD. Impairment is scored in each of 6 cognitive categories on a scale in which none = 0, questionable = 0.5, mild = 1, moderate = 2, and severe = 3. The 6 individual category ratings, or "box scores", can be added together to give the CDR-SB which ranges from 0 to 18 (severe impairment).
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Aug 2018
- Study start1 Aug 2019
- Primary completion19 Feb 2024
- Study completion19 Feb 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- 74 participants (actual)
Sponsor and investigators
- Lead sponsor
- Functional Neuromodulation Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03622905
- Sponsor's protocol ID
- FNMI-002
- Status last verified
- Nov 2024
- First submitted
- 1 Aug 2018
- Last updated
- 5 Nov 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- ADvance II: A 12-month Double-blind, Randomized, Controlled Study to Evaluate the Safety and Efficacy of Deep Brain Stimulation of the Fornix (DBS-f) in Patients With Mild Probable Alzheimer's Disease
- ClinicalTrials.gov ID
- NCT03622905
- Acronym / sponsor ID
- FNMI-002
- Conditions
- Alzheimer Disease
- Keywords
- Mild Probable Alzheimer's Disease
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 74 participants (actual)
- Lead sponsor
- Functional Neuromodulation LtdIndustry (pharma, biotech, devices)
- Study start
- 1 Aug 2019 (actual)
- Primary completion
- 19 Feb 2024 (actual)
- Study completion
- 19 Feb 2024 (actual)
- First posted
- 9 Aug 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
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 On | Experimental | Device: DBS-f OnDBS system On |
| DBS Off | Sham comparator | Device: DBS OffDBS System Off |
Who may qualify
- Ages
- 65 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (15 listed)
- 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).
Key exclusion criteria (15 listed)
- 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.
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 OnDeep Brain Stimulation of the fornix | Device | DBS On |
| DBS OffDeep Brain Stimulation of the fornix turned off | Device | DBS Off |
Primary outcome
Change From Baseline Over Time at 12 months on the Ingegrated Alzheimer's Disease Rating Scale (iADRS) [ Time Frame: From Baseline to month 12 ]
Time frame: 12 months
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.
1 secondary outcome
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 ]
Time frame: 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Nov 2024.
- Individual participant dataSharing planned: No
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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.
The record lists no contact. Use the official record to reach the sponsor.
21 sites in 3 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 Off in people with Alzheimer Disease, run by Functional Neuromodulation Ltd at 21 sites in 3 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 15 inclusion and 15 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 5 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 21 sites in United States, Germany, 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Change From Baseline Over Time at 12 months on the Ingegrated Alzheimer's Disease Rating Scale (iADRS) [ Time Frame: From Baseline to month 12 ] (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 5 Nov 2024.