Alzheimer Disease
Conditions
Keywords
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.
Interventions
DEVICEDBS-f on
deep brain stimulation of the fornix
DEVICEDBS-f off
deep brain stimulation of the fornix turned off
Sponsors
Functional Neuromodulation Ltd
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
45 Years to 85 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Acute Safety | 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. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ADAS-Cog 13 | 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 | 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. |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| DBS-f on DBS-f on
DBS-f on: deep brain stimulation of the fornix | 21 |
| DBS-f Off DBS-f off
DBS-f off: deep brain stimulation of the fornix turned off | 21 |
| Total | 42 |
Baseline characteristics
| Characteristic | Total | DBS-f Off | DBS-f on |
|---|---|---|---|
| ADAS-Cog 11 | 17 units on a scale | 17 units on a scale | 17 units on a scale |
| Age, Continuous | 69.9 years | 71.3 years | 68.1 years |
| CDR 0.5 | 28 Participants | 15 Participants | 13 Participants |
| CDR 1.0 | 14 Participants | 6 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 2 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 40 Participants | 19 Participants | 21 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 41 Participants | 20 Participants | 21 Participants |
| Sex: Female, Male Female | 19 Participants | 9 Participants | 10 Participants |
| Sex: Female, Male Male | 23 Participants | 12 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 21 | 0 / 21 |
| other Total, other adverse events | 19 / 21 | 17 / 21 |
| serious Total, serious adverse events | 8 / 21 | 8 / 21 |
Outcome results
Primary
Acute Safety
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.
Time frame: 30 days post implant
Population: All implanted subjects are used in this analysis. This analysis is of the entire population prior to randomization and thus cannot be analyzed per arm.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Implanted Subject | Acute Safety | 2 participants |
Primary
Long Term Safety. Not Based on Formal Hypotheses.
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.
Time frame: 12 month
Population: All randomized subjects are included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Implanted Subject | Long Term Safety. Not Based on Formal Hypotheses. | 0 participants |
| DBS-f Off | Long Term Safety. Not Based on Formal Hypotheses. | 1 participants |
Secondary
ADAS-Cog 13
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.
Time frame: Baseline and 12 months
Population: All randomized subjects
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Implanted Subject | ADAS-Cog 13 | 8.0 score on a scale | Standard Error 2.2 |
| DBS-f Off | ADAS-Cog 13 | 8.0 score on a scale | Standard Error 1.9 |
Secondary
CDR-SB
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.
Time frame: Baseline and 12 months
Population: All randomized subjects with available data. Two subjects in the ON group had missing CDR at 12 months.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Implanted Subject | CDR-SB | 2.5 score on a scale | Standard Error 0.4 |
| DBS-f Off | CDR-SB | 2.6 score on a scale | Standard Error 0.7 |