Trial Outcomes & Findings for ADvance DBS-f in Patients With Mild Probable Alzheimer's Disease (NCT NCT01608061)

Last Updated: 2020-08-31

Results Overview

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.

Recruitment status

COMPLETED

Study phase

Target enrollment

42 participants

Primary outcome timeframe

30 days post implant

Results posted on

2020-08-31

Participant Flow

Participant milestones

Participant milestones
Measure	DBS-f on DBS-f on DBS-f on: deep brain stimulation of the fornix	DBS-f Off DBS-f off DBS-f off: deep brain stimulation of the fornix turned off
Blinded Period STARTED	21	21
Blinded Period COMPLETED	21	21
Blinded Period NOT COMPLETED	0	0
Long Term Follow-Up STARTED	21	21
Long Term Follow-Up COMPLETED	14	16
Long Term Follow-Up NOT COMPLETED	7	5
Extension Period STARTED	14	16
Extension Period COMPLETED	14	14
Extension Period NOT COMPLETED	0	2

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	DBS-f on n=21 Participants DBS-f on DBS-f on: deep brain stimulation of the fornix	DBS-f Off n=21 Participants DBS-f off DBS-f off: deep brain stimulation of the fornix turned off	Total n=42 Participants Total of all reporting groups
Age, Continuous	68.1 years n=5 Participants	71.3 years n=7 Participants	69.9 years n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants	9 Participants n=7 Participants	19 Participants n=5 Participants
Sex: Female, Male Male	11 Participants n=5 Participants	12 Participants n=7 Participants	23 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	21 Participants n=5 Participants	19 Participants n=7 Participants	40 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	21 Participants n=5 Participants	20 Participants n=7 Participants	41 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
ADAS-Cog 11	17 units on a scale n=5 Participants	17 units on a scale n=7 Participants	17 units on a scale n=5 Participants
CDR 0.5	13 Participants n=5 Participants	15 Participants n=7 Participants	28 Participants n=5 Participants
CDR 1.0	8 Participants n=5 Participants	6 Participants n=7 Participants	14 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	All Implanted Subject n=42 Participants All implanted subjects are included in this group.	DBS-f Off DBS-f off DBS-f off: deep brain stimulation of the fornix turned off
Acute Safety	2 participants Interval 0.6 to 16.2	—

PRIMARY outcome

Timeframe: 12 month

Population: All randomized subjects are included.

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.

Outcome measures

Outcome measures
Measure	All Implanted Subject n=21 Participants All implanted subjects are included in this group.	DBS-f Off n=21 Participants DBS-f off DBS-f off: deep brain stimulation of the fornix turned off
Long Term Safety. Not Based on Formal Hypotheses.	0 participants Interval 0.0 to 16.1	1 participants Interval 0.1 to 23.8

SECONDARY outcome

Timeframe: Baseline and 12 months

Population: All randomized subjects

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.

Outcome measures

Outcome measures
Measure	All Implanted Subject n=21 Participants All implanted subjects are included in this group.	DBS-f Off n=21 Participants DBS-f off DBS-f off: deep brain stimulation of the fornix turned off
ADAS-Cog 13	8.0 score on a scale Standard Error 2.2	8.0 score on a scale Standard Error 1.9

SECONDARY outcome

Timeframe: Baseline and 12 months

Population: All randomized subjects with available data. Two subjects in the ON group had missing CDR at 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.

Outcome measures

Outcome measures
Measure	All Implanted Subject n=19 Participants All implanted subjects are included in this group.	DBS-f Off n=21 Participants DBS-f off DBS-f off: deep brain stimulation of the fornix turned off
CDR-SB	2.5 score on a scale Standard Error 0.4	2.6 score on a scale Standard Error 0.7

Adverse Events

DBS-f on

Serious events: 8 serious events

Other events: 19 other events

Deaths: 1 deaths

DBS-f Off

Serious events: 8 serious events

Other events: 17 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Todd Langevin

Functional Neuromodulation

Phone: 7636071214

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Serious adverse events
Measure	DBS-f on n=21 participants at risk DBS-f on DBS-f on: deep brain stimulation of the fornix	DBS-f Off n=21 participants at risk DBS-f off DBS-f off: deep brain stimulation of the fornix turned off
Infections and infestations UTI	0.00% 0/21 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).	4.8% 1/21 • Number of events 1 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).
General disorders Headache	4.8% 1/21 • Number of events 1 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).	0.00% 0/21 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).
Gastrointestinal disorders Nausea and vomiting	4.8% 1/21 • Number of events 1 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).	0.00% 0/21 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).
Nervous system disorders Seizure	4.8% 1/21 • Number of events 2 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).	0.00% 0/21 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).
Nervous system disorders Syncope	4.8% 1/21 • Number of events 1 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).	14.3% 3/21 • Number of events 4 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).
Nervous system disorders Altered mental status	4.8% 1/21 • Number of events 1 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).	4.8% 1/21 • Number of events 1 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).
Nervous system disorders Fall	4.8% 1/21 • Number of events 1 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).	9.5% 2/21 • Number of events 2 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).
Infections and infestations Skin infection	4.8% 1/21 • Number of events 1 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).	0.00% 0/21 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).
Infections and infestations Bacteremia	4.8% 1/21 • Number of events 1 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).	0.00% 0/21 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).
Musculoskeletal and connective tissue disorders Increased rigidity	4.8% 1/21 • Number of events 1 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).	0.00% 0/21 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).
Cardiac disorders myocardial infarction with stent	4.8% 1/21 • Number of events 1 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).	0.00% 0/21 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).
Infections and infestations Pneumonia	4.8% 1/21 • Number of events 1 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).	0.00% 0/21 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).
Psychiatric disorders Agitation	0.00% 0/21 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).	4.8% 1/21 • Number of events 1 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).
Psychiatric disorders Depression	0.00% 0/21 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).	4.8% 1/21 • Number of events 1 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).
Psychiatric disorders Confusion	0.00% 0/21 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).	4.8% 1/21 • Number of events 1 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).
Psychiatric disorders Suicidal Ideation	0.00% 0/21 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).	4.8% 1/21 • Number of events 1 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).
Infections and infestations Device infection	9.5% 2/21 • Number of events 3 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).	4.8% 1/21 • Number of events 1 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).
Surgical and medical procedures Abnormal MRI	0.00% 0/21 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).	4.8% 1/21 • Number of events 1 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).
Surgical and medical procedures Subdural hematoma	0.00% 0/21 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).	4.8% 1/21 • Number of events 1 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).
Surgical and medical procedures Lead misplacement	4.8% 1/21 • Number of events 1 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).	0.00% 0/21 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).

Other adverse events
Measure	DBS-f on n=21 participants at risk DBS-f on DBS-f on: deep brain stimulation of the fornix	DBS-f Off n=21 participants at risk DBS-f off DBS-f off: deep brain stimulation of the fornix turned off
Nervous system disorders Agitation	9.5% 2/21 • Number of events 2 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).	9.5% 2/21 • Number of events 4 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).
Nervous system disorders Anxiety	9.5% 2/21 • Number of events 2 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).	9.5% 2/21 • Number of events 6 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).
Skin and subcutaneous tissue disorders Basal Cell Carcinoma	0.00% 0/21 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).	9.5% 2/21 • Number of events 2 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).
Psychiatric disorders Change in Mental Status	4.8% 1/21 • Number of events 1 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).	4.8% 1/21 • Number of events 1 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).
Infections and infestations Respiratory Infection	23.8% 5/21 • Number of events 9 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).	19.0% 4/21 • Number of events 6 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).
Nervous system disorders Confusion	14.3% 3/21 • Number of events 3 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).	28.6% 6/21 • Number of events 7 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).
Skin and subcutaneous tissue disorders Contact Dermatitis	4.8% 1/21 • Number of events 1 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).	4.8% 1/21 • Number of events 1 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).
Psychiatric disorders Delerium	4.8% 1/21 • Number of events 1 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).	4.8% 1/21 • Number of events 1 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).
Psychiatric disorders Depression	28.6% 6/21 • Number of events 6 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).	19.0% 4/21 • Number of events 6 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).
Gastrointestinal disorders Diarrhea	9.5% 2/21 • Number of events 2 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).	14.3% 3/21 • Number of events 4 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).
General disorders Dizziness	4.8% 1/21 • Number of events 1 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).	9.5% 2/21 • Number of events 2 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).
General disorders Epistaxis	14.3% 3/21 • Number of events 3 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).	0.00% 0/21 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).
General disorders Fall	9.5% 2/21 • Number of events 2 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).	23.8% 5/21 • Number of events 17 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).
General disorders Fatigue	19.0% 4/21 • Number of events 4 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).	19.0% 4/21 • Number of events 4 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).
Gastrointestinal disorders Fecal Incontinence	4.8% 1/21 • Number of events 1 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).	9.5% 2/21 • Number of events 2 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).
General disorders Headache	28.6% 6/21 • Number of events 7 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).	33.3% 7/21 • Number of events 7 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).
General disorders Insomnia	9.5% 2/21 • Number of events 2 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).	19.0% 4/21 • Number of events 4 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).
Nervous system disorders Irritability	9.5% 2/21 • Number of events 2 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).	4.8% 1/21 • Number of events 1 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).
General disorders Lethargy	0.00% 0/21 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).	9.5% 2/21 • Number of events 2 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).
General disorders Migraine	9.5% 2/21 • Number of events 3 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).	0.00% 0/21 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).
General disorders Nausea	19.0% 4/21 • Number of events 4 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).	19.0% 4/21 • Number of events 4 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).
Musculoskeletal and connective tissue disorders Neck Pain	4.8% 1/21 • Number of events 1 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).	4.8% 1/21 • Number of events 1 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).
Psychiatric disorders Paranoid Ideation	4.8% 1/21 • Number of events 3 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).	4.8% 1/21 • Number of events 1 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).
Nervous system disorders Seizure	9.5% 2/21 • Number of events 6 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).	0.00% 0/21 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).
General disorders Shortness of Breath	9.5% 2/21 • Number of events 2 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).	0.00% 0/21 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).
Renal and urinary disorders Urinary Tract Infection	14.3% 3/21 • Number of events 3 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).	4.8% 1/21 • Number of events 1 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).
Renal and urinary disorders Urinary Retention	4.8% 1/21 • Number of events 1 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).	9.5% 2/21 • Number of events 2 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).
Renal and urinary disorders Urinary Incontenance	0.00% 0/21 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).	9.5% 2/21 • Number of events 2 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).
Psychiatric disorders visual Hallucinations	4.8% 1/21 • Number of events 1 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).	14.3% 3/21 • Number of events 5 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).
Gastrointestinal disorders Vomiting	14.3% 3/21 • Number of events 3 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).	4.8% 1/21 • Number of events 1 • Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months. An independent Clinical Events Committee (CEC) reviewed all reported adverse events. The CEC was responsible for conducting a review of all adverse events reported for study subjects. The CEC will adjudicate and classify all events for relatedness to the study system, study procedure and study requirements. The CEC will determine if any serious device-related adverse event is an unanticipated adverse device effect (UADE).