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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03622905
Recruitment Status : Recruiting
First Posted : August 9, 2018
Last Update Posted : November 24, 2020
Sponsor:
Information provided by (Responsible Party):
Functional Neuromodulation Ltd

Tracking Information
First Submitted Date  ICMJE August 1, 2018
First Posted Date  ICMJE August 9, 2018
Last Update Posted Date November 24, 2020
Actual Study Start Date  ICMJE August 1, 2019
Estimated Primary Completion Date October 1, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 8, 2018)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 8, 2018)
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).
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE ADvance II Study: DBS-f in Patients With Mild Alzheimer's Disease
Official Title  ICMJE 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
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).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Alzheimer Disease
Intervention  ICMJE
  • Device: DBS-f On
    Deep Brain Stimulation of the fornix
  • Device: DBS Off
    Deep Brain Stimulation of the fornix turned off
Study Arms  ICMJE
  • Experimental: DBS On
    DBS system On
    Intervention: Device: DBS-f On
  • Sham Comparator: DBS Off
    DBS System Off
    Intervention: Device: DBS Off
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 9, 2019)
210
Original Estimated Enrollment  ICMJE
 (submitted: August 8, 2018)
282
Estimated Study Completion Date  ICMJE October 1, 2024
Estimated Primary Completion Date October 1, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Informed consent signed by the subject and caregiver.
  2. At least 65 years old
  3. Probable Alzheimer's disease according to 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. Confirmation of Alzheimer's disease based on CSF biomarkers.
  7. 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.
  8. Patient must be a good surgical candidate for placement of a deep brain stimulator as judged by the DBS surgical team.
  9. Fluency (oral and written) in the language in which standardized tests will be administered.
  10. The patient is either

    1. 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
    2. 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).

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 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.
  4. 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.
  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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 65 Years and older   (Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Kristen Drake 214-543-8321 kdrake@fxneuromod.com
Contact: Robyn Moxon rmoxon@fxneuromod.com
Listed Location Countries  ICMJE Canada,   Germany,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03622905
Other Study ID Numbers  ICMJE FNMI-002
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Functional Neuromodulation Ltd
Study Sponsor  ICMJE Functional Neuromodulation Ltd
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Functional Neuromodulation Ltd
Verification Date November 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP