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ADvance II Study: DBS-f in Patients With Mild Alzheimer's Disease

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ClinicalTrials.gov Identifier: NCT03622905
Recruitment Status : Recruiting
First Posted : August 9, 2018
Last Update Posted : August 14, 2019
Sponsor:
Information provided by (Responsible Party):
Functional Neuromodulation Ltd

Brief 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).

Condition or disease Intervention/treatment Phase
Alzheimer Disease Device: DBS-f On Device: DBS Off Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 282 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : August 1, 2019
Estimated Primary Completion Date : October 1, 2023
Estimated Study Completion Date : October 1, 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: DBS On
DBS system On
Device: DBS-f On
Deep Brain Stimulation of the fornix

Sham Comparator: DBS Off
DBS System Off
Device: DBS Off
Deep Brain Stimulation of the fornix turned off




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  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 ] [ Time Frame: 12 months ]
    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).



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Ages Eligible for Study:   65 Years and older   (Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Informed consent signed by the subject and caregiver.
  2. At least 65 years of age.
  3. Probable Alzheimer's disease according the National Institute of Aging Alzheimer's disease Association criteria.
  4. Mild dementia according to the Clinical Dementia Rating (CDR) global rating of 0.5 or 1 at screening.
  5. ADAS-cog-11 score of 10-24 inclusive at screening AND baseline (with a score ≥ 4 on ADAS-cog item 1).
  6. Moderate to marked elevation in CSF tau per the central lab
  7. Moderate to marked decrement in CSF Aβ per the central lab
  8. 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.
  9. Patient must be a good surgical candidate for placement of a deep brain stimulator as judged by the DBS surgical team.
  10. Fluency (oral and written) in the language in which standardized tests will be administered.
  11. The patient is 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 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).

Exclusion Criteria:

  1. NPI total score ≥ 10 or score ≥ 4 in any NPI domain (clinically significant neuropsychiatric symptoms). Apathy score ≥ 4 acceptable.
  2. Modified Hachinski ischemia scale score > 4 at screening
  3. At risk for suicide in the opinion of the investigator or 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 in the 2 years before screening.
  4. Suffers from a current 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
  5. History of moderate or more severe traumatic brain injury in the 2 years prior to signing the consent to participate in the study
  6. History of brain tumor, subdural hematoma, or other clinically significant (in the judgment of the investigator) space-occupying lesion on CT or MRI
  7. History of seizure disorder.
  8. Contraindications for PET scanning (e.g., insulin dependent diabetes)
  9. 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.
  10. 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.
  11. Abnormal cardiovascular or neurovascular disorder that, in the opinion of the investigator would preclude participation in the study.
  12. Currently prescribed any non-AD medications that, in the opinion of the investigator would preclude participation in the study.
  13. Is unable or unwilling to comply with protocol follow-up requirements.
  14. Has a life expectancy of < 1 year.
  15. Is actively enrolled in another concurrent clinical trial. -

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03622905


Contacts
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Contact: Robyn Moxon 651-246-6941 rmoxon@fxneuromod.com
Contact: Lisa Fosdick, MS 6513381747 lfosdick@fxneuromod.com

Locations
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United States, Arizona
Barrow Neurological Institute Recruiting
Phoenix, Arizona, United States, 85013
Contact: Jennifer Wilde    602-406-3386    Jennifer.Wilde@DignityHealth.org   
Principal Investigator: Anna Burke, MD         
United States, California
University of Southern California Recruiting
Los Angeles, California, United States, 90033
Contact: Sandra Oviedo    323-865-9873    sandra.oviedo@med.usc.edu   
Principal Investigator: Darrin Lee, MD         
Stanford University Recruiting
Stanford, California, United States, 94305
Contact: Vyvian Ngo    650-498-0817    vyviann@stanford.edu   
Principal Investigator: Casey Halpern, MD         
United States, Florida
University of Florida Recruiting
Gainesville, Florida, United States, 32601
Contact: Camille Swartz    352-273-5612    Cami.Swartz@neurology.ufl.edu   
Principal Investigator: Adolfo Ramirez, MD         
Germany
Universitätmedizin Charité Berlin Recruiting
Berlin, Germany
Contact: Claudia Altendorf    004930450660226    claudia.altendorf@charite.de   
Principal Investigator: Andrea Kühn, M.D.         
Universitätklinikum Köln Recruiting
Cologne, Germany
Contact: Elfriede Stubbs    0049-221-47898842    elfriede.stubbs@uk-koeln.de   
Principal Investigator: Veere Visser-Vandewalle, M.D.         
Klinik für Neurologie Universitätsklinikum Recruiting
Kiel, Germany
Contact: Birte Hackelberg    0049-431-50023989    Birte.Hackelberg@uksh.de   
Principal Investigator: Steffen Paschen, M.D.         
Universität Magdeburg Recruiting
Magdeburg, Germany
Contact: Urte Schneider    0049-391-6724601    Urte.Schneider@dzne.de   
Principal Investigator: Jürgen Voges, M.D.         
Technische Universität München Recruiting
Munich, Germany
Contact: Friederike Schels    00498941404276    Friederike.schels@mri.tum.de   
Principal Investigator: Timo Grimmer, M.D.         
Universitätklinikum Würzburg Recruiting
Würzburg, Germany
Contact: Anne-Marie Ilita    0049-931-20124805    Ilita_A@ukw.de   
Principal Investigator: Cordula Matthies, M.D.         
Sponsors and Collaborators
Functional Neuromodulation Ltd

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Responsible Party: Functional Neuromodulation Ltd
ClinicalTrials.gov Identifier: NCT03622905     History of Changes
Other Study ID Numbers: FNMI-002
First Posted: August 9, 2018    Key Record Dates
Last Update Posted: August 14, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: No

Keywords provided by Functional Neuromodulation Ltd:
Mild Probable Alzheimer's Disease

Additional relevant MeSH terms:
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Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders