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

August 21, 2020 updated by: Functional Neuromodulation Ltd

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

42

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5T 2S8
        • Toronto Western Hospital
  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85006
        • Banner Alzheimer's Institute
      • Sun City, Arizona, United States, 85351
        • Banner Research Institute at Sun City
    • Florida
      • Gainesville, Florida, United States, 32607
        • University of Florida at Gainesville
    • Maryland
      • Baltimore, Maryland, United States, 21224
        • Johns Hopkins Bayview
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Hospital of the University of Pennsylvania: Penn Memory Clinic
    • Rhode Island
      • Providence, Rhode Island, United States, 02906
        • Brown University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

45 years to 85 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: DBS-f on
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
SHAM_COMPARATOR: DBS-f off
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
30 days post implant
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.
12 month

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Baseline and 12 months
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.
Baseline and 12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Functional Neuromodulation Ltd

Investigators

  • Principal Investigator: Constantine G Lyketsos, MD, MHS, DFAPA, FAPM, Johns Hopkins University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

May 1, 2012

Primary Completion (ACTUAL)

June 1, 2015

Study Completion (ACTUAL)

September 1, 2018

Study Registration Dates

First Submitted

May 21, 2012

First Submitted That Met QC Criteria

May 29, 2012

First Posted (ESTIMATE)

May 30, 2012

Study Record Updates

Last Update Posted (ACTUAL)

August 31, 2020

Last Update Submitted That Met QC Criteria

August 21, 2020

Last Verified

August 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FNMI-001

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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