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

• ClinicalTrials.gov Identifier: NCT01608061
• Recruitment Status: Completed
• First Posted: May 30, 2012
• Results First Posted: August 31, 2020
• Last Update Posted: August 31, 2020
• Sponsor: Functional Neuromodulation Ltd
• Information provided by (Responsible Party): Functional Neuromodulation Ltd

Tracking Information

• First Submitted Date: May 21, 2012
• First Posted Date: May 30, 2012
• Results First Submitted Date: February 18, 2020
• Results First Posted Date: August 31, 2020
• Last Update Posted Date: August 31, 2020
• Actual Study Start Date: May 2012
• Actual Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 21, 2020)

• 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.

• Original Primary Outcome Measures (submitted: May 29, 2012): The study will assess the acute and long-term safety of the system. A detailed assessment of all device and/or therapy related adverse events will be conducted. [ Time Frame: 12 month ]

Current Secondary Outcome Measures (submitted: August 21, 2020)

• ADAS-Cog 13 [ Time Frame: Baseline and 12 months ]
  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.
• CDR-SB [ Time Frame: Baseline and 12 months ]
  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.

• Original Secondary Outcome Measures (submitted: May 29, 2012): Efficacy outcomes include: improvement in ADAS-cog 13 at twelve months, improvement in the CDR and changes in glucose metabolism measured by FDG-PET at twelve months [ Time Frame: twelve months ]
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: ADvance DBS-f in Patients With Mild Probable Alzheimer's Disease
• 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
• Brief 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Alzheimer Disease

Intervention

• Device: DBS-f on
  deep brain stimulation of the fornix
  Other Names:

  • 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
• Device: DBS-f off
  deep brain stimulation of the fornix turned off
  Other Names:

  • 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

Study Arms

• Experimental: DBS-f on
  DBS-f on
  Intervention: Device: DBS-f on
• Sham Comparator: DBS-f off
  DBS-f off
  Intervention: Device: DBS-f off

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.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 21, 2020): 42
• Original Estimated Enrollment (submitted: May 29, 2012): 20
• Actual Study Completion Date: September 2018
• Actual Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. 45-85 years of age (inclusive)
2. Probable Alzheimer's disease according to the National Institute of Aging Alzheimer's disease Association criteria.
3. Must meet certain criteria on cognitive and behavioral rating scales
4. If female, subjects who are post-menopausal or surgically sterile or willing to use birth control methods for the duration of the study.
5. An available caregiver willing to participate.
6. Subject is living at home and likely to remain at home for the study duration.
7. The subject is currently taking a stable dose of cholinesterase inhibitor (AChEI) medication for at least 60 days

Exclusion Criteria:

1. Must meet certain criteria on cognitive and behavioral rating scales
2. Current major psychiatric disorder such as schizophrenia, bipolar disorder or major depressive disorder based on psychiatric consult at screening visit
3. History of head trauma in the 2 years prior to signing the consent to participate in the study
4. History of brain tumor, subdural hematoma, or other clinically significant (in the judgment of the investigator) space-occupying lesion on CT or MRI
5. Active psychiatric disorder
6. Mental retardation
7. Current alcohol or substance abuse as defined by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR)
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. Abnormal lab results that, in the opinion of the investigator and/or enrollment review committee, would preclude participation in the study.
11. Abnormal cardiovascular or neurovascular disorder that, in the opinion of the investigator and/or enrollment review committee, would preclude participation in the study.
12. Unstable doses of any medication prescribed for the treatment of memory loss or Alzheimer's disease.
13. Currently prescribed any non-AD medications that, in the opinion of the investigator and/or enrollment review committee, would preclude participation in the study.
14. Is unable or unwilling to comply with protocol follow-up requirements.
15. Has a life expectancy of < 1 year.
16. Is actively enrolled in another concurrent clinical trial.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 45 Years to 85 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, United States

Administrative Information

• NCT Number: NCT01608061
• Other Study ID Numbers: FNMI-001
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Functional Neuromodulation Ltd
• Original Responsible Party: Same as current
• Current Study Sponsor: Functional Neuromodulation Ltd
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Andres Lozano, MD, PhD; University Health Network, Toronto
• Principal Investigator: Constantine G Lyketsos, MD, MHS, DFAPA, FAPM; Johns Hopkins University

• PRS Account: Functional Neuromodulation Ltd
• Verification Date: August 2020