Parkinson Disease
Conditions
Keywords
Deep Brain Stimulation, Parkinson's Disease
Brief summary
The purpose of the study is to demonstrate the safety and effectiveness of adaptive DBS (aDBS) for Parkinson's disease.
Detailed description
Prospective single-blind, randomized crossover, multi-center study of aDBS in subjects with Parkinson's disease.
Interventions
DEVICEAdaptive DBS
Subjects for whom both aDBS modes are acceptable will receive Dual and Single Threshold aDBS
Sponsors
MedtronicNeuro
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Intervention model description
Randomization to a crossover sequence of aDBS single threshold and aDBS dual threshold modes
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
General 1. Subject has idiopathic Parkinson's disease 2. Subject is implanted with Percept PC (Model B35200) and Medtronic Deep Brain Stimulation (DBS) leads (Model 3387, 3389, B33005 or B33015) and extensions (Model 37085, 37086, or B34000) bilaterally in the same target (physician confirmed), subthalamic nucleus (STN) or Globus Pallidus (GPi) 3. In the opinion of the investigator, the subject responds to DBS Therapy. 4. Based on the opinion of the investigator, the subject's cDBS parameters and PD medications are stable and expected to remain stable from enrollment through the end of the aDBS Evaluation phase 5. (Primary Cohort) Subject is configured to ring mode monopolar or dual monopolar stimulation using contacts 1 and/or 2 (9 and/or 10) on at least one side. 5\. (Directional Stimulation Cohort) Subject is configured to directional monopolar or dual monopolar stimulation using contacts 1 and/or 2 (9 and/or 10) 6. Subject is willing and able to attend all study-required visits and complete the study procedures (e.g. 1-month recall questionnaires, MDS-UPDRS III) 7. Subject has the ability to understand and provide written informed consent for participation in the study prior to the study-related procedures being conducted 8. Subject is a male or non-pregnant female. If female of child-bearing potential, and if sexually active, must be using, or agree to use, a medically-acceptable method of birth control as confirmed by the investigator 9. For subjects with the SenSight system: Subject is configured to the following stimulation rates: 55, 85, 110, 125, 145, 164 or 180 Hz (as required for sensing/aDBS) Local Field Potential (LFP) Screening Inclusion Criteria 1\. Subject has required Alpha-Beta band (8-30 Hz) amplitude ≥ 1.2 µVp detected on either left and/or right DBS leads
Exclusion criteria
1. Subject and/or caregiver is unable to utilize the patient programmer 2. Subject has more than one lead in each hemisphere of the brain 3. Subject has cortical leads or additional unapproved hardware implanted in the brain 4. Subject has more than one INS 5. At enrollment, the subject's INS has a predicted battery life of \<1 year 6. Subject has Beck Depression Inventory II (BDI-II) \> 25 7. Subject requires diathermy, transcranial magnetic stimulation (TMS), or electroconvulsive therapy (ECT) 8. Subject has a metallic implant in the head, (eg, aneurysm clip, cochlear implant) 9. Subject has, or plans to obtain, an implanted electrical stimulation medical device anywhere in the body (eg, cardiac pacemaker, defibrillator, spinal cord stimulator) 10. Subject has, or plans to obtain, an implanted medication pump for the treatment of Parkinson's disease (eg, DUOPATM infusion pump) and/or portable infusion pump 11. Based on the opinion of the investigator, the subject has an abnormal neurological examination that would preclude them from study participation 12. Subject is breast feeding 13. Subject is under the age of 18 years 14. Subject is currently enrolled in or plans to enroll in any concurrent drug and/or device study that may confound the results of this study as determined by the Medtronic study team 15. Subject is unable to use or tolerate wearable 16. Subjects with signal artifact on all 6 aDBS sense pathways (3 each on both DBS leads) which preclude the clinician from setting thresholds
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of aDBS Subjects With On Time Without Troublesome Dyskinesia Exceeding the Threshold. | About one month | In the PD Home Diary, in 30-minute intervals, patients recorded whether they were in the On condition (with dyskinesia, with non-troublesome dyskinesia, with troublesome dyskinesia), Off condition, or asleep. The On time without troublesome dyskinesia combined the categories of On time without dyskinesia and On time with non-troublesome dyskinesia. The PD Home Diary was collected at both the cDBS Baseline and aDBS Evaluation Phases. The threshold was determined using the hours of On time without troublesome dyskinesia for aDBS is no worse than 2 hours per day less than cDBS. The proportion of aDBS subjects exceeding the threshold was the primary endpoint. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Stimulation Energy Use | About one month | Total electrical energy delivered (TEED) for aDBS as compared with cDBS, calculated as TEED at aDBS - TEED at cDBS. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Safety (Stimulation-related AEs) | About one month | To characterize stimulation-related adverse events |
Countries
Canada, France, Netherlands, United States
Participant flow
Recruitment details
85 subjects were enrolled between December 14, 2020 and July 29, 2022 at 12 centers located in the US, Europe, and Canada. Out of these 85 subjects, 68 were in Primary Cohort and 17 in Directional Stimulation Cohort.
Pre-assignment details
60 out of 85 subjects entered into the aDBS Evaluation Phase of the study. Of those 25 who didn't enter into the aDBS Evaluation Phase, 1 had inclusion/exclusion screen failure, 12 LFP screen failures, 4 physician decisions, and 8 subject decisions.
Participants by arm
| Arm | Count |
|---|---|
| Primary Cohort, Crossover Sequence 1: aDBS Single Threshold Mode, Then aDBS Dual Threshold Mode This cohort comprised of study subjects implanted with legacy lead model 3387 or 3389, or with SenSight™ lead model B33005 or B33015 programmed to ring mode stimulation, received Single Threshold evaluation for about one month first, then Dual Threshold evaluation for about one month. | 16 |
| Primary Cohort, Crossover Sequence 2: aDBS Dual Threshold Mode, Then aDBS Single Threshold Mode This cohort comprised of study subjects implanted with legacy lead model 3387 or 3389, or with SenSight™ lead model B33005 or B33015 programmed to ring mode stimulation, received Dual Threshold evaluation for about one month first, then Single Threshold evaluation for about one month. | 14 |
| Primary Cohort, One Mode: aDBS Single Threshold Mode This cohort comprised of study subjects implanted with legacy lead model 3387 or 3389, or with SenSight™ lead model B33005 or B33015 programmed to ring mode stimulation, received only Single Threshold evaluation for about one month. | 5 |
| Primary Cohort, One Mode: aDBS Dual Threshold Mode This cohort comprised of study subjects implanted with legacy lead model 3387 or 3389, or with SenSight™ lead model B33005 or B33015 programmed to ring mode stimulation, received only Dual Threshold evaluation for about one month. | 10 |
| Directional Stimulation Cohort, Crossover Sequence 1: aDBS Single, Then aDBS Dual Threshold Mode This cohort comprised of study subjects with SenSight™ lead model B33005 or B33015 programmed to directional stimulation, with Single and/or Dual Threshold evaluation for about one month. | 6 |
| Directional Stimulation Cohort, Crossover Sequence 2: aDBS Dual, Then aDBS Single Threshold Mode This cohort comprised of study subjects with SenSight™ lead model B33005 or B33015 programmed to directional stimulation, with Single and/or Dual Threshold evaluation for about one month. | 7 |
| Directional Stimulation Cohort, One Mode: aDBS Dual Threshold Mode This cohort comprised of study subjects with SenSight™ lead model B33005 or B33015 programmed to directional stimulation, with Dual Threshold evaluation for about one month. | 2 |
| Total | 60 |
Baseline characteristics
| Characteristic | Primary Cohort, Crossover Sequence 2: aDBS Dual Threshold Mode, Then aDBS Single Threshold Mode | Primary Cohort, One Mode: aDBS Single Threshold Mode | Primary Cohort, One Mode: aDBS Dual Threshold Mode | Directional Stimulation Cohort, Crossover Sequence 1: aDBS Single, Then aDBS Dual Threshold Mode | Primary Cohort, Crossover Sequence 1: aDBS Single Threshold Mode, Then aDBS Dual Threshold Mode | Directional Stimulation Cohort, Crossover Sequence 2: aDBS Dual, Then aDBS Single Threshold Mode | Directional Stimulation Cohort, One Mode: aDBS Dual Threshold Mode | Total |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 64.2 years STANDARD_DEVIATION 7.62 | 59.6 years STANDARD_DEVIATION 7.16 | 59.6 years STANDARD_DEVIATION 10.08 | 59.7 years STANDARD_DEVIATION 4.18 | 60.6 years STANDARD_DEVIATION 9.49 | 61.0 years STANDARD_DEVIATION 8.08 | 58.0 years STANDARD_DEVIATION 2.83 | 61.1 years STANDARD_DEVIATION 8.15 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants | 2 Participants | 7 Participants | 5 Participants | 13 Participants | 6 Participants | 2 Participants | 45 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants | 3 Participants | 3 Participants | 0 Participants | 3 Participants | 0 Participants | 0 Participants | 12 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 3 Participants | 3 Participants | 1 Participants | 3 Participants | 1 Participants | 0 Participants | 14 Participants |
| Race (NIH/OMB) White | 11 Participants | 2 Participants | 5 Participants | 4 Participants | 13 Participants | 6 Participants | 2 Participants | 43 Participants |
| Region of Enrollment Canada | 2 participants | 0 participants | 2 participants | 0 participants | 0 participants | 0 participants | 0 participants | 4 participants |
| Region of Enrollment France | 0 participants | 1 participants | 0 participants | 0 participants | 1 participants | 0 participants | 0 participants | 2 participants |
| Region of Enrollment Netherlands | 1 participants | 2 participants | 1 participants | 0 participants | 2 participants | 0 participants | 0 participants | 6 participants |
| Region of Enrollment United States | 11 participants | 2 participants | 7 participants | 6 participants | 13 participants | 7 participants | 2 participants | 48 participants |
| Sex: Female, Male Female | 5 Participants | 4 Participants | 2 Participants | 1 Participants | 4 Participants | 2 Participants | 1 Participants | 19 Participants |
| Sex: Female, Male Male | 9 Participants | 1 Participants | 8 Participants | 5 Participants | 12 Participants | 5 Participants | 1 Participants | 41 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 85 | 1 / 35 | 0 / 40 | 0 / 13 | 0 / 15 |
| other Total, other adverse events | 32 / 85 | 10 / 35 | 16 / 40 | 4 / 13 | 5 / 15 |
| serious Total, serious adverse events | 0 / 85 | 1 / 35 | 0 / 40 | 0 / 13 | 0 / 15 |
Outcome results
Primary
Proportion of aDBS Subjects With On Time Without Troublesome Dyskinesia Exceeding the Threshold.
In the PD Home Diary, in 30-minute intervals, patients recorded whether they were in the On condition (with dyskinesia, with non-troublesome dyskinesia, with troublesome dyskinesia), Off condition, or asleep. The On time without troublesome dyskinesia combined the categories of On time without dyskinesia and On time with non-troublesome dyskinesia. The PD Home Diary was collected at both the cDBS Baseline and aDBS Evaluation Phases. The threshold was determined using the hours of On time without troublesome dyskinesia for aDBS is no worse than 2 hours per day less than cDBS. The proportion of aDBS subjects exceeding the threshold was the primary endpoint.
Time frame: About one month
Population: As pre-specified, the analysis population included only Primary Cohort subjects, following the intention-to-treat principle, who initiated the aDBS Evaluation Phase (including both randomized crossover subjects and one mode subjects). Analysis of the primary endpoint is based on the aDBS mode (Single or Dual Threshold) by pooling subjects from randomized crossover and one mode arms. As pre-specified, Directional Stimulation Cohort was not included in the primary objective analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Primary Cohort aDBS Single Threshold | Proportion of aDBS Subjects With On Time Without Troublesome Dyskinesia Exceeding the Threshold. | 78.9 percentage of participant |
| Primary Cohort aDBS Dual Threshold | Proportion of aDBS Subjects With On Time Without Troublesome Dyskinesia Exceeding the Threshold. | 91 percentage of participant |
Comparison: Null Hypothesis: The proportion of subjects with On time without troublesome dyskinesia during aDBS single threshold mode Evaluation Period exceeding threshold \<= 50%; Alternative Hypothesis: The proportion of subjects with On time without troublesome dyskinesia during aDBS single threshold mode Evaluation Period exceeding threshold \> 50%
Comparison: Null Hypothesis: The proportion of subjects with On time without troublesome dyskinesia during aDBS dual threshold mode Evaluation Period exceeding threshold \<= 50%; Alternative Hypothesis: The proportion of subjects with On time without troublesome dyskinesia during aDBS dual threshold mode Evaluation Period exceeding threshold \> 50%
Secondary
Stimulation Energy Use
Total electrical energy delivered (TEED) for aDBS as compared with cDBS, calculated as TEED at aDBS - TEED at cDBS.
Time frame: About one month
Population: As pre-specified, the analysis population included only Primary Cohort subjects, following the intention-to-treat principle, who initiated the aDBS Evaluation Phase (including both randomized crossover subjects and one mode subjects). Analysis of the primary endpoint is based on the aDBS mode (Single or Dual Threshold) by pooling subjects from randomized crossover and one mode arms. As pre-specified, Directional Stimulation Cohort was not included in the secondary objective analysis.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Primary Cohort aDBS Single Threshold | Stimulation Energy Use | -22.3 micro Watts |
| Primary Cohort aDBS Dual Threshold | Stimulation Energy Use | -22.3 micro Watts |
Comparison: Null Hypothesis: Mean Difference between aDBS single threshold (Evaluation Phase) minus cDBS (Baseline Phase) for TEED \>= 0; Alternative Hypothesis: Mean Difference between aDBS single threshold (Evaluation Phase) minus cDBS (Baseline Phase) for TEED \< 0p-value: 0.012t-test, 2 sided
Comparison: Null Hypothesis: Mean Difference between aDBS dual threshold (Evaluation Phase) minus cDBS (Baseline Phase) for TEED \>= 0; Alternative Hypothesis: Mean Difference between aDBS dual threshold (Evaluation Phase) minus cDBS (Baseline Phase) for TEED \< 0p-value: 0.0491t-test, 2 sided
Other Pre-specified
Safety (Stimulation-related AEs)
To characterize stimulation-related adverse events
Time frame: About one month
Population: As pre-specified, the analysis population included only Primary Cohort subjects, following the intention-to-treat principle, who initiated the aDBS Evaluation Phase (including both randomized crossover subjects and one mode subjects). Analysis of the primary endpoint is based on the aDBS mode (Single or Dual Threshold) by pooling subjects from randomized crossover and one mode arms. As pre-specified, Directional Stimulation Cohort was not included in the analysis of this objective.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Primary Cohort aDBS Single Threshold | Safety (Stimulation-related AEs) | 3 Participants |
| Primary Cohort aDBS Dual Threshold | Safety (Stimulation-related AEs) | 8 Participants |
| Primary Cohort: aDBS Dual Threshold Mode | Safety (Stimulation-related AEs) | 5 Participants |