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Trial record 1 of 1 for:    NCT01608061
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ADvance DBS-f in Patients With Mild Probable Alzheimer's Disease (ADvance)

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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:
Information provided by (Responsible Party):
Functional Neuromodulation Ltd

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Alzheimer Disease
Interventions Device: DBS-f on
Device: DBS-f off
Enrollment 42
Recruitment Details  
Pre-assignment Details  
Arm/Group Title DBS-f on DBS-f Off
Hide Arm/Group Description

DBS-f on

DBS-f on: deep brain stimulation of the fornix

DBS-f off

DBS-f off: deep brain stimulation of the fornix turned off

Period Title: Blinded Period
Started 21 21
Completed 21 21
Not Completed 0 0
Period Title: Long Term Follow-Up
Started 21 21
Completed 14 16
Not Completed 7 5
Period Title: Extension Period
Started 14 16
Completed 14 14
Not Completed 0 2
Arm/Group Title DBS-f on DBS-f Off Total
Hide Arm/Group Description

DBS-f on

DBS-f on: deep brain stimulation of the fornix

DBS-f off

DBS-f off: deep brain stimulation of the fornix turned off

Total of all reporting groups
Overall Number of Baseline Participants 21 21 42
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 21 participants 21 participants 42 participants
68.1
(51.1 to 79.7)
71.3
(48.0 to 78.0)
69.9
(48.0 to 79.7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 21 participants 21 participants 42 participants
Female
10
  47.6%
9
  42.9%
19
  45.2%
Male
11
  52.4%
12
  57.1%
23
  54.8%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 21 participants 21 participants 42 participants
Hispanic or Latino
0
   0.0%
2
   9.5%
2
   4.8%
Not Hispanic or Latino
21
 100.0%
19
  90.5%
40
  95.2%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 21 participants 21 participants 42 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
White
21
 100.0%
20
  95.2%
41
  97.6%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
1
   4.8%
1
   2.4%
ADAS-Cog 11   [1] 
Median (Full Range)
Unit of measure:  Units on a scale
Number Analyzed 21 participants 21 participants 42 participants
17
(13 to 22)
17
(12 to 21)
17
(12 to 22)
[1]
Measure Description: Alzheimer's Disease Assessment Scale-Cognitive Subscale 11 (ADAS-Cog 11). The cognitive subscale (ADAS-Cog) includes 11 tasks that include both subject-completed tests and observer-based assessments.Together these tasks assess the cognitive domains of memory, language, and praxis. Single scale from 0 to 70 where a higher score indicates more advanced disease.
CDR   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 21 participants 21 participants 42 participants
0.5 13 15 28
1.0 8 6 14
[1]
Measure Description: Clinical Dementia Rating scale (CDR). The CDR is a 5-point scale used to characterize six domains of cognitive and functional performance applicable to Alzheimer disease and related dementias: Memory, Orientation, Judgment & Problem Solving, Community Affairs, Home & Hobbies, and Personal Care. The necessary information to make each rating is obtained through a semi-structured interview of the patient and a reliable informant or collateral source (e.g., family member). Range is 0 to 3 with a higher score indicating more advanced disease.
1.Primary Outcome
Title Acute Safety
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title All Implanted Subject
Hide Arm/Group Description:
All implanted subjects are included in this group.
Overall Number of Participants Analyzed 42
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: participants
2
(0.6 to 16.2)
2.Primary Outcome
Title Long Term Safety. Not Based on Formal Hypotheses.
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized subjects are included.
Arm/Group Title DBS-f on DBS-f Off
Hide Arm/Group Description:

DBS-f on

DBS-f on: deep brain stimulation of the fornix

DBS-f off

DBS-f off: deep brain stimulation of the fornix turned off

Overall Number of Participants Analyzed 21 21
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: participants
0
(0 to 16.1)
1
(0.1 to 23.8)
3.Secondary Outcome
Title ADAS-Cog 13
Hide Description

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
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized subjects
Arm/Group Title DBS-f on DBS-f Off
Hide Arm/Group Description:

DBS-f on

DBS-f on: deep brain stimulation of the fornix

DBS-f off

DBS-f off: deep brain stimulation of the fornix turned off

Overall Number of Participants Analyzed 21 21
Mean (Standard Error)
Unit of Measure: score on a scale
8.0  (2.2) 8.0  (1.9)
4.Secondary Outcome
Title CDR-SB
Hide Description

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
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized subjects with available data. Two subjects in the ON group had missing CDR at 12 months.
Arm/Group Title DBS-f on DBS-f Off
Hide Arm/Group Description:

DBS-f on

DBS-f on: deep brain stimulation of the fornix

DBS-f off

DBS-f off: deep brain stimulation of the fornix turned off

Overall Number of Participants Analyzed 19 21
Mean (Standard Error)
Unit of Measure: score on a scale
2.5  (0.4) 2.6  (0.7)
Time Frame Adverse events were collected from the time of consent until study exit for each subject. Maximum duration was 48 months.
Adverse Event Reporting Description 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).
 
Arm/Group Title DBS-f on DBS-f Off
Hide Arm/Group Description

DBS-f on

DBS-f on: deep brain stimulation of the fornix

DBS-f off

DBS-f off: deep brain stimulation of the fornix turned off

All-Cause Mortality
DBS-f on DBS-f Off
Affected / at Risk (%) Affected / at Risk (%)
Total   1/21 (4.76%)      0/21 (0.00%)    
Hide Serious Adverse Events
DBS-f on DBS-f Off
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   8/21 (38.10%)      8/21 (38.10%)    
Cardiac disorders     
myocardial infarction with stent   1/21 (4.76%)  1 0/21 (0.00%)  0
Gastrointestinal disorders     
Nausea and vomiting   1/21 (4.76%)  1 0/21 (0.00%)  0
General disorders     
Headache   1/21 (4.76%)  1 0/21 (0.00%)  0
Infections and infestations     
UTI  [1]  0/21 (0.00%)  0 1/21 (4.76%)  1
Skin infection   1/21 (4.76%)  1 0/21 (0.00%)  0
Bacteremia  [2]  1/21 (4.76%)  1 0/21 (0.00%)  0
Pneumonia   1/21 (4.76%)  1 0/21 (0.00%)  0
Device infection   2/21 (9.52%)  3 1/21 (4.76%)  1
Musculoskeletal and connective tissue disorders     
Increased rigidity   1/21 (4.76%)  1 0/21 (0.00%)  0
Nervous system disorders     
Seizure   1/21 (4.76%)  2 0/21 (0.00%)  0
Syncope   1/21 (4.76%)  1 3/21 (14.29%)  4
Altered mental status   1/21 (4.76%)  1 1/21 (4.76%)  1
Fall   1/21 (4.76%)  1 2/21 (9.52%)  2
Psychiatric disorders     
Agitation   0/21 (0.00%)  0 1/21 (4.76%)  1
Depression   0/21 (0.00%)  0 1/21 (4.76%)  1
Confusion   0/21 (0.00%)  0 1/21 (4.76%)  1
Suicidal Ideation   0/21 (0.00%)  0 1/21 (4.76%)  1
Surgical and medical procedures     
Abnormal MRI   0/21 (0.00%)  0 1/21 (4.76%)  1
Subdural hematoma  [3]  0/21 (0.00%)  0 1/21 (4.76%)  1
Lead misplacement   1/21 (4.76%)  1 0/21 (0.00%)  0
Indicates events were collected by systematic assessment
[1]
Urinary tract infection
[2]
suspected aortic valve endocarditis
[3]
bilateral subacute and chronic
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
DBS-f on DBS-f Off
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   19/21 (90.48%)      17/21 (80.95%)    
Gastrointestinal disorders     
Diarrhea   2/21 (9.52%)  2 3/21 (14.29%)  4
Fecal Incontinence   1/21 (4.76%)  1 2/21 (9.52%)  2
Vomiting   3/21 (14.29%)  3 1/21 (4.76%)  1
General disorders     
Dizziness   1/21 (4.76%)  1 2/21 (9.52%)  2
Epistaxis   3/21 (14.29%)  3 0/21 (0.00%)  0
Fall   2/21 (9.52%)  2 5/21 (23.81%)  17
Fatigue   4/21 (19.05%)  4 4/21 (19.05%)  4
Headache   6/21 (28.57%)  7 7/21 (33.33%)  7
Insomnia   2/21 (9.52%)  2 4/21 (19.05%)  4
Lethargy   0/21 (0.00%)  0 2/21 (9.52%)  2
Migraine   2/21 (9.52%)  3 0/21 (0.00%)  0
Nausea   4/21 (19.05%)  4 4/21 (19.05%)  4
Shortness of Breath   2/21 (9.52%)  2 0/21 (0.00%)  0
Infections and infestations     
Respiratory Infection   5/21 (23.81%)  9 4/21 (19.05%)  6
Musculoskeletal and connective tissue disorders     
Neck Pain   1/21 (4.76%)  1 1/21 (4.76%)  1
Nervous system disorders     
Agitation   2/21 (9.52%)  2 2/21 (9.52%)  4
Anxiety   2/21 (9.52%)  2 2/21 (9.52%)  6
Confusion   3/21 (14.29%)  3 6/21 (28.57%)  7
Irritability   2/21 (9.52%)  2 1/21 (4.76%)  1
Seizure   2/21 (9.52%)  6 0/21 (0.00%)  0
Psychiatric disorders     
Change in Mental Status   1/21 (4.76%)  1 1/21 (4.76%)  1
Delerium   1/21 (4.76%)  1 1/21 (4.76%)  1
Depression   6/21 (28.57%)  6 4/21 (19.05%)  6
Paranoid Ideation   1/21 (4.76%)  3 1/21 (4.76%)  1
visual Hallucinations   1/21 (4.76%)  1 3/21 (14.29%)  5
Renal and urinary disorders     
Urinary Tract Infection   3/21 (14.29%)  3 1/21 (4.76%)  1
Urinary Retention   1/21 (4.76%)  1 2/21 (9.52%)  2
Urinary Incontenance   0/21 (0.00%)  0 2/21 (9.52%)  2
Skin and subcutaneous tissue disorders     
Basal Cell Carcinoma   0/21 (0.00%)  0 2/21 (9.52%)  2
Contact Dermatitis   1/21 (4.76%)  1 1/21 (4.76%)  1
Indicates events were collected by systematic assessment
While this feasibility trial was randomized it was not designed with formal hypotheses nor was it powered for analyses.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Todd Langevin
Organization: Functional Neuromodulation
Phone: 7636071214
EMail: todd@fxneuromod.com
Layout table for additonal information
Responsible Party: Functional Neuromodulation Ltd
ClinicalTrials.gov Identifier: NCT01608061    
Other Study ID Numbers: FNMI-001
First Submitted: May 21, 2012
First Posted: May 30, 2012
Results First Submitted: February 18, 2020
Results First Posted: August 31, 2020
Last Update Posted: August 31, 2020