Trial Outcomes & Findings for Asymmetric Subthalamic Deep Brain Stimulation for Axial Motor Dysfunction in Parkinson's Disease (NCT NCT03462082)
NCT ID: NCT03462082
Last Updated: 2021-01-05
Results Overview
As measured during the 10-meter walk test. In this test, participants walk at their usual, regular pace over a total distance of 10 meters. The middle 6-meters (between the 2-meter and 8-meter marks) are timed to measure gait velocity during steady-state gait.
COMPLETED
NA
22 participants
Baseline and 3 to 4 weeks after switching to each of the DBS conditions (Bilateral, Asymmetric 1, Asymmetric 2)
2021-01-05
Participant Flow
38 patients with Parkinson's disease (PD) who developed postural instability gait dysfunction (PIGD) after bilateral subthalamic (STN) deep brain stimulation (DBS) were screened for eligibility between January 22, 2018 and January 29, 2019 at the DBS clinic of the Movement Disorders Center at the University of Toronto in Toronto, Ontario, Canada.
22 of 38 patients were enrolled. Of the 16 patients not enrolled, 9 did not meet inclusion criteria and 7 declined to participate. There were no significant events between enrollment and randomization. The first study participant was enrolled on March 14, 2018. The last study participant was enrolled on January 29, 2019.
Participant milestones
| Measure |
Bilateral DBS Then Asymmetric DBS 1 Then Asymmetric DBS 2
Baseline bilateral STN-DBS for 3 to 4 weeks, followed by asymmetric STN-DBS 1 (right STN-DBS amplitude reduced by 50%) for 3 to 4 weeks, followed by asymmetric STN-DBS 2 (left STN-DBS amplitude reduced by 50%) for 3 to 4 weeks.
|
Bilateral DBS Then Asymmetric DBS 2 Then Asymmetric DBS 1
Baseline bilateral STN-DBS for 3 to 4 weeks, followed by asymmetric STN-DBS 2 (left STN-DBS amplitude reduced by 50%) for 3 to 4 weeks, followed by asymmetric STN-DBS 1 (right STN-DBS amplitude reduced by 50%) for 3 to 4 weeks.
|
Asymmetric DBS 1 Then Bilateral DBS Then Asymmetric DBS 2
Asymmetric STN-DBS 1 (right STN amplitude reduced by 50%) for 3 to 4 weeks, followed by baseline bilateral STN-DBS for 3 to 4 weeks, followed by asymmetric STN-DBS 2 (left STN-DBS amplitude reduced by 50%) for 3 to 4 weeks.
|
Asymmetric DBS 1 Then Asymmetric DBS 2 Then Bilateral DBS
Asymmetric STN-DBS 1 (right STN-DBS amplitude reduced by 50%) for 3 to 4 weeks, followed by asymmetric STN-DBS 2 (left STN-DBS amplitude reduced by 50%) for 3 to 4 weeks, followed by baseline bilateral STN-DBS for 3 to 4 weeks.
|
Asymmetric DBS 2 Then Bilateral DBS Then Asymmetric DBS 1
Asymmetric STN-DBS 2 (left STN-DBS amplitude reduced by 50%) for 3 to 4 weeks, followed by baseline bilateral STN-DBS for 3 to 4 weeks, followed by asymmetric STN-DBS 1 (right STN-DBS amplitude reduced by 50%) for 3 to 4 weeks.
|
Asymmetric DBS 2 Then Asymmetric DBS 1 Then Bilateral DBS
Asymmetric STN-DBS 2 (left STN-DBS amplitude reduced by 50%) for 3 to 4 weeks, followed by asymmetric STN-DBS 1 (right STN-DBS amplitude reduced by 50%) for 3 to 4 weeks, followed by baseline bilateral STN-DBS for 3 to 4 weeks.
|
Asymmetric DBS 1 (Open Label)
After the Study Phase (Randomized, Blinded Period) was completed, patients were offered to participate in an Open Label Phase in which they would be switched for at least 12 weeks to either the Asymmetric DBS 1 or the Asymmetric DBS 2 condition if it was associated with axial symptom improvement when compared to their baseline bilateral DBS condition.
Out of the 22 patients initially enrolled, 17 opted to participate. Out of the 17 patients that opted to participate, 7 were switched to the Asymmetric DBS 1 condition: 50% reduction of right STN-DBS amplitude (voltage)
|
Asymmetric DBS 2 (Open Label)
After the Study Phase (Randomized, Blinded Period) was completed, patients were offered to participate in an Open Label Phase in which they would be switched for at least 12 weeks to either the Asymmetric DBS 1 or the Asymmetric DBS 2 condition if it was associated with axial symptom improvement when compared to their baseline bilateral DBS condition.
Out of the 22 patients initially enrolled, 17 opted to participate. Out of the 17 patients that opted to participate, 10 were switched to the Asymmetric DBS 2 condition: 50% reduction of left STN-DBS amplitude (voltage)
|
|---|---|---|---|---|---|---|---|---|
|
Study Phase (Randomized, Blinded Period)
STARTED
|
3
|
4
|
4
|
3
|
3
|
5
|
0
|
0
|
|
Study Phase (Randomized, Blinded Period)
COMPLETED
|
3
|
4
|
4
|
3
|
3
|
5
|
0
|
0
|
|
Study Phase (Randomized, Blinded Period)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Open Label Phase
STARTED
|
0
|
0
|
0
|
0
|
0
|
0
|
7
|
10
|
|
Open Label Phase
COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
6
|
8
|
|
Open Label Phase
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
1
|
2
|
Reasons for withdrawal
| Measure |
Bilateral DBS Then Asymmetric DBS 1 Then Asymmetric DBS 2
Baseline bilateral STN-DBS for 3 to 4 weeks, followed by asymmetric STN-DBS 1 (right STN-DBS amplitude reduced by 50%) for 3 to 4 weeks, followed by asymmetric STN-DBS 2 (left STN-DBS amplitude reduced by 50%) for 3 to 4 weeks.
|
Bilateral DBS Then Asymmetric DBS 2 Then Asymmetric DBS 1
Baseline bilateral STN-DBS for 3 to 4 weeks, followed by asymmetric STN-DBS 2 (left STN-DBS amplitude reduced by 50%) for 3 to 4 weeks, followed by asymmetric STN-DBS 1 (right STN-DBS amplitude reduced by 50%) for 3 to 4 weeks.
|
Asymmetric DBS 1 Then Bilateral DBS Then Asymmetric DBS 2
Asymmetric STN-DBS 1 (right STN amplitude reduced by 50%) for 3 to 4 weeks, followed by baseline bilateral STN-DBS for 3 to 4 weeks, followed by asymmetric STN-DBS 2 (left STN-DBS amplitude reduced by 50%) for 3 to 4 weeks.
|
Asymmetric DBS 1 Then Asymmetric DBS 2 Then Bilateral DBS
Asymmetric STN-DBS 1 (right STN-DBS amplitude reduced by 50%) for 3 to 4 weeks, followed by asymmetric STN-DBS 2 (left STN-DBS amplitude reduced by 50%) for 3 to 4 weeks, followed by baseline bilateral STN-DBS for 3 to 4 weeks.
|
Asymmetric DBS 2 Then Bilateral DBS Then Asymmetric DBS 1
Asymmetric STN-DBS 2 (left STN-DBS amplitude reduced by 50%) for 3 to 4 weeks, followed by baseline bilateral STN-DBS for 3 to 4 weeks, followed by asymmetric STN-DBS 1 (right STN-DBS amplitude reduced by 50%) for 3 to 4 weeks.
|
Asymmetric DBS 2 Then Asymmetric DBS 1 Then Bilateral DBS
Asymmetric STN-DBS 2 (left STN-DBS amplitude reduced by 50%) for 3 to 4 weeks, followed by asymmetric STN-DBS 1 (right STN-DBS amplitude reduced by 50%) for 3 to 4 weeks, followed by baseline bilateral STN-DBS for 3 to 4 weeks.
|
Asymmetric DBS 1 (Open Label)
After the Study Phase (Randomized, Blinded Period) was completed, patients were offered to participate in an Open Label Phase in which they would be switched for at least 12 weeks to either the Asymmetric DBS 1 or the Asymmetric DBS 2 condition if it was associated with axial symptom improvement when compared to their baseline bilateral DBS condition.
Out of the 22 patients initially enrolled, 17 opted to participate. Out of the 17 patients that opted to participate, 7 were switched to the Asymmetric DBS 1 condition: 50% reduction of right STN-DBS amplitude (voltage)
|
Asymmetric DBS 2 (Open Label)
After the Study Phase (Randomized, Blinded Period) was completed, patients were offered to participate in an Open Label Phase in which they would be switched for at least 12 weeks to either the Asymmetric DBS 1 or the Asymmetric DBS 2 condition if it was associated with axial symptom improvement when compared to their baseline bilateral DBS condition.
Out of the 22 patients initially enrolled, 17 opted to participate. Out of the 17 patients that opted to participate, 10 were switched to the Asymmetric DBS 2 condition: 50% reduction of left STN-DBS amplitude (voltage)
|
|---|---|---|---|---|---|---|---|---|
|
Open Label Phase
Symptom worsening (Treatment failure)
|
0
|
0
|
0
|
0
|
0
|
0
|
1
|
2
|
Baseline Characteristics
Two patients could not complete cognitive tasks due to language barrier.
Baseline characteristics by cohort
| Measure |
All Study Participants
n=22 Participants
All Study Participants
|
|---|---|
|
Age, Continuous
|
65.5 years
n=22 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=22 Participants
|
|
Sex: Female, Male
Male
|
15 Participants
n=22 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=22 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
22 Participants
n=22 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=22 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=22 Participants
|
|
Race (NIH/OMB)
Asian
|
5 Participants
n=22 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=22 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=22 Participants
|
|
Race (NIH/OMB)
White
|
17 Participants
n=22 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=22 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=22 Participants
|
|
Region of Enrollment
Canada
|
22 Participants
n=22 Participants
|
|
Hand dominance
|
82.5 units on a scale
n=22 Participants
|
|
Parkinson's disease duration
|
17 years
n=22 Participants
|
|
Predominant motor symptom at onset
Tremor
|
9 Participants
n=22 Participants
|
|
Predominant motor symptom at onset
Stiffness and/or Slowness
|
13 Participants
n=22 Participants
|
|
More affected hemibody at onset
Right
|
13 Participants
n=22 Participants
|
|
More affected hemibody at onset
Left
|
8 Participants
n=22 Participants
|
|
More affected hemibody at onset
Both
|
1 Participants
n=22 Participants
|
|
Indication for STN-DBS surgery
Medication-resistant tremor
|
8 Participants
n=22 Participants
|
|
Indication for STN-DBS surgery
Medication-resistant motor fluctuations
|
14 Participants
n=22 Participants
|
|
Time since STN-DBS surgery
|
51 months
n=22 Participants
|
|
Time between STN-DBS surgery and onset of axial dysfunction
|
14.5 months
n=22 Participants
|
|
More affected hemibody at enrollment
Right
|
4 Participants
n=22 Participants
|
|
More affected hemibody at enrollment
Left
|
4 Participants
n=22 Participants
|
|
More affected hemibody at enrollment
Both
|
14 Participants
n=22 Participants
|
|
Levodopa equivalent daily dose
|
1037.5 mg/day
n=22 Participants
|
|
Baseline right STN-DBS type
Conventional monopolar
|
1 Participants
n=22 Participants
|
|
Baseline right STN-DBS type
Low-frequency monopolar
|
8 Participants
n=22 Participants
|
|
Baseline right STN-DBS type
High-frequency monopolar
|
3 Participants
n=22 Participants
|
|
Baseline right STN-DBS type
Interleaving low-frequency monopolar
|
4 Participants
n=22 Participants
|
|
Baseline right STN-DBS type
Double low-frequency monopolar
|
1 Participants
n=22 Participants
|
|
Baseline right STN-DBS type
Interleaving low-frequency monopolar/double monop.
|
1 Participants
n=22 Participants
|
|
Baseline right STN-DBS type
Conventional bipolar
|
1 Participants
n=22 Participants
|
|
Baseline right STN-DBS type
Low-frequency bipolar
|
2 Participants
n=22 Participants
|
|
Baseline right STN-DBS type
High-frequency bipolar
|
0 Participants
n=22 Participants
|
|
Baseline right STN-DBS type
Interleaving conventional monopolar / bipolar
|
1 Participants
n=22 Participants
|
|
Baseline right STN-DBS amplitude
|
3.95 Volts
n=22 Participants
|
|
Baseline right STN-DBS frequency
|
80 Hertz
n=22 Participants
|
|
Baseline right STN-DBS pulse width
|
60 Microseconds
n=22 Participants
|
|
Baseline total electrical energy delivered (TEED) to the right STN
|
88.59 Joules/second
n=22 Participants
|
|
Baseline left STN-DBS type
Conventional monopolar
|
0 Participants
n=22 Participants
|
|
Baseline left STN-DBS type
Low-frequency monopolar
|
8 Participants
n=22 Participants
|
|
Baseline left STN-DBS type
High-frequency monopolar
|
1 Participants
n=22 Participants
|
|
Baseline left STN-DBS type
Interleaving low-frequency monopolar
|
4 Participants
n=22 Participants
|
|
Baseline left STN-DBS type
Double low-frequency monopolar
|
0 Participants
n=22 Participants
|
|
Baseline left STN-DBS type
Interleaving low-frequency monopolar/double monop.
|
1 Participants
n=22 Participants
|
|
Baseline left STN-DBS type
Conventional bipolar
|
2 Participants
n=22 Participants
|
|
Baseline left STN-DBS type
Low-frequency bipolar
|
3 Participants
n=22 Participants
|
|
Baseline left STN-DBS type
High-frequency bipolar
|
2 Participants
n=22 Participants
|
|
Baseline left STN-DBS type
Interleaving conventional monopolar / bipolar
|
1 Participants
n=22 Participants
|
|
Baseline left STN-DBS amplitude
|
4.08 Volts
n=22 Participants
|
|
Baseline left STN-DBS frequency
|
80 Hertz
n=22 Participants
|
|
Baseline left STN-DBS pulse width
|
60 Microseconds
n=22 Participants
|
|
Baseline total electrical energy delivered (TEED) to the left STN
|
89.66 Joules/second
n=22 Participants
|
|
Gait velocity
|
0.976 m/s
n=22 Participants
|
|
MDS-UPDRS (total)
|
89 units on a scale
n=22 Participants
|
|
MDS-UPDRS (motor)
|
45.5 units on a scale
n=22 Participants
|
|
MDS-UPDRS (axial motor)
|
16.5 units on a scale
n=22 Participants
|
|
Mini-BESTest score
|
15 units on a scale
n=22 Participants
|
|
UPDRS-PIGD score
|
11 units on a scale
n=22 Participants
|
|
Freezing of gait questionnaire
|
14.5 units on a scale
n=22 Participants
|
|
Summary index of the PDQ-39
|
31.54 units on a scale
n=22 Participants
|
|
Select cognitive tasks
HopkinsVerbalLearningTest-Revised: RecallTrials1-3
|
21.75 units on a scale
STANDARD_DEVIATION 5.78 • n=20 Participants • Two patients could not complete cognitive tasks due to language barrier.
|
|
Select cognitive tasks
HopkinsVerbal LearningTest-Revised: Delayed Recall
|
7.70 units on a scale
STANDARD_DEVIATION 2.56 • n=20 Participants • Two patients could not complete cognitive tasks due to language barrier.
|
|
Select cognitive tasks
Phonemic Verbal Fluency
|
31.50 units on a scale
STANDARD_DEVIATION 14.15 • n=20 Participants • Two patients could not complete cognitive tasks due to language barrier.
|
|
Select cognitive tasks
Semantic Verbal Fluency (Animal cue)
|
16.80 units on a scale
STANDARD_DEVIATION 7.82 • n=20 Participants • Two patients could not complete cognitive tasks due to language barrier.
|
|
Select cognitive tasks
Letter 1-Back Working Memory Task
|
82.86 units on a scale
STANDARD_DEVIATION 18.51 • n=20 Participants • Two patients could not complete cognitive tasks due to language barrier.
|
|
Select cognitive tasks
Letter 2-Back Working Memory Task
|
55.11 units on a scale
STANDARD_DEVIATION 26.28 • n=20 Participants • Two patients could not complete cognitive tasks due to language barrier.
|
|
Select cognitive tasks
Brief Visual Memory Test-Revised: RecallTrials 1-3
|
12.75 units on a scale
STANDARD_DEVIATION 6.24 • n=20 Participants • Two patients could not complete cognitive tasks due to language barrier.
|
|
Select cognitive tasks
Brief Visual Memory Test-Revised: Delayed Recall
|
5.15 units on a scale
STANDARD_DEVIATION 3.38 • n=20 Participants • Two patients could not complete cognitive tasks due to language barrier.
|
|
Select cognitive tasks
Computerized landmark line bisection task
|
0.08 units on a scale
STANDARD_DEVIATION 0.53 • n=20 Participants • Two patients could not complete cognitive tasks due to language barrier.
|
|
Select cognitive tasks
Spatial 1-Back Working Memory Task
|
85.20 units on a scale
STANDARD_DEVIATION 23.22 • n=20 Participants • Two patients could not complete cognitive tasks due to language barrier.
|
|
Select cognitive tasks
Spatial 2-Back Working Memory Task
|
57.81 units on a scale
STANDARD_DEVIATION 29.10 • n=20 Participants • Two patients could not complete cognitive tasks due to language barrier.
|
PRIMARY outcome
Timeframe: Baseline and 3 to 4 weeks after switching to each of the DBS conditions (Bilateral, Asymmetric 1, Asymmetric 2)Population: Bilateral (baseline) values are the average of the outcome measure data obtained during the 2 bilateral (baseline) conditions: 1) at enrollment before randomization and 2) after randomization. These average values are used to report the changes associated with the 2 asymmetric conditions.
As measured during the 10-meter walk test. In this test, participants walk at their usual, regular pace over a total distance of 10 meters. The middle 6-meters (between the 2-meter and 8-meter marks) are timed to measure gait velocity during steady-state gait.
Outcome measures
| Measure |
Bilateral STN-DBS
n=22 Participants
Bilateral (baseline) STN-DBS settings
|
Asymmetric STN-DBS 1
n=22 Participants
50% reduction of right STN-DBS amplitude (voltage)
|
Asymmetric STN-DBS 2
n=22 Participants
50% reduction of left STN-DBS amplitude (voltage)
|
|---|---|---|---|
|
Change in Gait Velocity
|
0.941 m/s
Standard Error 0.086
|
-0.069 m/s
Standard Error 0.048
|
-0.016 m/s
Standard Error 0.048
|
SECONDARY outcome
Timeframe: Baseline and 3 to 4 weeks after switching to each of the DBS conditions (Bilateral, Asymmetric 1, Asymmetric 2)Population: Bilateral (baseline) values are the average of the outcome measure data obtained during the 2 bilateral (baseline) conditions: 1) at enrollment before randomization and 2) after randomization. These average values are used to compare the changes associated with the 2 asymmetric conditions.
As measured by the MDS-UPDRS (Movement Disorders Society Unified Parkinson's Disease Rating Scale), which is a clinical and research tool to measure symptoms and signs of Parkinson's disease. It has 4 parts: I (non-motor experiences of daily living), II (motor experiences of daily living), III (motor exam) and IV (motor complications). The MDS-UPDRS has 60 items, scored from 0-4 each. The minimum score is 0 and the maximum score is 240. The MDS-UPDRS (motor) is Part III and measures motor signs. It has 28 items, scored from 0-4 each, so the minimum score is 0 and the maximum score is 112. The MDS-UPDRS (axial motor) is composed of items 3.1 to 3.3a and 3.9 to 3.13 of Part III of the MDS-UPDRS and measures axial motor signs. It has 8 items, scored from 0-4 each, so the minimum score is 0 and the maximum score is 32. In the MDS-UPDRS total, motor and axial motor sub-scales, lower scores indicate better symptoms/signs and higher scores indicate worse symptoms/signs, respectively.
Outcome measures
| Measure |
Bilateral STN-DBS
n=22 Participants
Bilateral (baseline) STN-DBS settings
|
Asymmetric STN-DBS 1
n=22 Participants
50% reduction of right STN-DBS amplitude (voltage)
|
Asymmetric STN-DBS 2
n=22 Participants
50% reduction of left STN-DBS amplitude (voltage)
|
|---|---|---|---|
|
Change in Motor Function
MDS-UPDRS (total)
|
1.032 units on a scale
Standard Error 0.093
|
10.058 units on a scale
Standard Error 4.491
|
1.277 units on a scale
Standard Error 4.491
|
|
Change in Motor Function
MDS-UPDRS (motor)
|
1.080 units on a scale
Standard Error 0.086
|
4.582 units on a scale
Standard Error 2.147
|
1.636 units on a scale
Standard Error 2.147
|
|
Change in Motor Function
MDS-UPDRS (axial motor)
|
0.947 units on a scale
Standard Error 0.074
|
-1.342 units on a scale
Standard Error 0.823
|
-2.453 units on a scale
Standard Error 0.823
|
SECONDARY outcome
Timeframe: Baseline and 3 to 4 weeks after switching to each of the DBS conditions (Bilateral, Asymmetric 1, Asymmetric 2)Population: Bilateral (baseline) values are the average of the outcome measure data obtained during the 2 bilateral (baseline) conditions: 1) at enrollment before randomization and 2) after randomization. These average values are used to report the changes associated with the 2 asymmetric conditions.
As measured by the Mini-BESTest. The Mini-BESTest is a shorter version of the BESTest (Balance Evaluation Systems Test). It is a clinical and research tool to measure balance control. The Mini-BESTest has 14 items, scored from 0-2 each, so the minimum score is 0 and the maximum score is 28. Lower scores indicate worse balance control and higher scores indicate better balance control.
Outcome measures
| Measure |
Bilateral STN-DBS
n=22 Participants
Bilateral (baseline) STN-DBS settings
|
Asymmetric STN-DBS 1
n=22 Participants
50% reduction of right STN-DBS amplitude (voltage)
|
Asymmetric STN-DBS 2
n=22 Participants
50% reduction of left STN-DBS amplitude (voltage)
|
|---|---|---|---|
|
Change in Axial Motor Function (1)
|
0.967 units on a scale
Standard Error 0.068
|
-0.017 units on a scale
Standard Error 0.828
|
1.557 units on a scale
Standard Error 0.828
|
SECONDARY outcome
Timeframe: Baseline and 3 to 4 weeks after switching to each of the DBS conditions (Bilateral, Asymmetric 1, Asymmetric 2)Population: Bilateral (baseline) values are the average of the outcome measure data obtained during the 2 bilateral (baseline) conditions: 1) at enrollment before randomization and 2) after randomization. These average values are used to compare the changes associated with the 2 asymmetric conditions.
As measured by the UPDRS-PIGD sub-scale. The UPDRS-PIGD is the Postural Instability Gait Dysfunction (PIGD) sub-scale of the Unified Parkinson's Disease Rating Scale (UPDRS). It is a clinical and research tool to measure PIGD. The UPDRS-PIGD has 5 items, scored from 0-4 each, so the minimum score is 0 and the maximum score is 20. Lower scores indicate better PIGD and higher scores indicate worse PIGD.
Outcome measures
| Measure |
Bilateral STN-DBS
n=22 Participants
Bilateral (baseline) STN-DBS settings
|
Asymmetric STN-DBS 1
n=22 Participants
50% reduction of right STN-DBS amplitude (voltage)
|
Asymmetric STN-DBS 2
n=22 Participants
50% reduction of left STN-DBS amplitude (voltage)
|
|---|---|---|---|
|
Change in Axial Motor Function (2)
|
0.909 units on a scale
Standard Error 0.153
|
-0.549 units on a scale
Standard Error 0.704
|
-1.414 units on a scale
Standard Error 0.704
|
SECONDARY outcome
Timeframe: Baseline and 3 to 4 weeks after switching to each of the DBS conditions (Bilateral, Asymmetric 1, Asymmetric 2)Population: Bilateral (baseline) values are the average of the outcome measure data obtained during the 2 bilateral (baseline) conditions: 1) at enrollment before randomization and 2) after randomization. These average values are used to compare the changes associated with the 2 asymmetric conditions.
As measured by the Freezing of Gait Questionnaire. The Freezing of Gait Questionnaire is a clinical and research tool to measure freezing of gait. It has 6 items, scored from 0-4 each, so the minimum score is 0 and the maximum score is 24. Lower scores indicate better and higher scores indicate worse freezing of gait, respectively.
Outcome measures
| Measure |
Bilateral STN-DBS
n=22 Participants
Bilateral (baseline) STN-DBS settings
|
Asymmetric STN-DBS 1
n=22 Participants
50% reduction of right STN-DBS amplitude (voltage)
|
Asymmetric STN-DBS 2
n=22 Participants
50% reduction of left STN-DBS amplitude (voltage)
|
|---|---|---|---|
|
Change in Axial Motor Function (3)
|
0.837 units on a scale
Standard Error 0.088
|
-0.056 units on a scale
Standard Error 0.807
|
-1.888 units on a scale
Standard Error 0.807
|
SECONDARY outcome
Timeframe: Baseline and 3 to 4 weeks after switching to each of the DBS conditions (Bilateral, Asymmetric 1, Asymmetric 2)Population: Bilateral (baseline) values are the average of the outcome measure data obtained during the 2 bilateral (baseline) conditions: 1) at enrollment before randomization and 2) after randomization. These average values are used to compare the changes associated with the 2 asymmetric conditions.
Changes in gait velocity in m/s as measured by a quantitative gait analysis system (Zeno walkway).
Outcome measures
| Measure |
Bilateral STN-DBS
n=22 Participants
Bilateral (baseline) STN-DBS settings
|
Asymmetric STN-DBS 1
n=22 Participants
50% reduction of right STN-DBS amplitude (voltage)
|
Asymmetric STN-DBS 2
n=22 Participants
50% reduction of left STN-DBS amplitude (voltage)
|
|---|---|---|---|
|
Change in Quantitative Gait Analysis (1)
|
0.814 m/s
Standard Error 0.095
|
-6.635 m/s
Standard Error 3.910
|
-1.254 m/s
Standard Error 3.910
|
SECONDARY outcome
Timeframe: Baseline and 3 to 4 weeks after switching to each of the DBS conditions (Bilateral, Asymmetric 1, Asymmetric 2)Population: Bilateral (baseline) values are the average of the outcome measure data obtained during the 2 bilateral (baseline) conditions: 1) at enrollment before randomization and 2) after randomization. These average values are used to compare the changes associated with the 2 asymmetric conditions.
Changes in step length in cm (mean, right, left) as measured by a quantitative gait analysis system (Zeno walkway). Step length difference = \[right - left step length\]
Outcome measures
| Measure |
Bilateral STN-DBS
n=22 Participants
Bilateral (baseline) STN-DBS settings
|
Asymmetric STN-DBS 1
n=22 Participants
50% reduction of right STN-DBS amplitude (voltage)
|
Asymmetric STN-DBS 2
n=22 Participants
50% reduction of left STN-DBS amplitude (voltage)
|
|---|---|---|---|
|
Change in Quantitative Gait Analysis (2)
Step length (mean)
|
0.975 cm
Standard Error 0.129
|
-3.097 cm
Standard Error 1.990
|
-3.191 cm
Standard Error 1.990
|
|
Change in Quantitative Gait Analysis (2)
Step length (right)
|
0.899 cm
Standard Error 0.156
|
-2.867 cm
Standard Error 1.931
|
-3.800 cm
Standard Error 1.931
|
|
Change in Quantitative Gait Analysis (2)
Step length (left)
|
1.015 cm
Standard Error 0.115
|
-3.293 cm
Standard Error 2.252
|
-3.493 cm
Standard Error 2.252
|
|
Change in Quantitative Gait Analysis (2)
Step length difference
|
0.731 cm
Standard Error 0.138
|
0.426 cm
Standard Error 1.088
|
-0.307 cm
Standard Error 1.088
|
SECONDARY outcome
Timeframe: Baseline and 3 to 4 weeks after switching to each of the DBS conditions (Bilateral, Asymmetric 1, Asymmetric 2)Population: Bilateral (baseline) values are the average of the outcome measure data obtained during the 2 bilateral (baseline) conditions: 1) at enrollment before randomization and 2) after randomization. These average values are used to compare the changes associated with the 2 asymmetric conditions.
Step length ratio = \[right step length\] / \[left step length\] Step length symmetry = (\[right - left step length\] / \[right + left step length\])
Outcome measures
| Measure |
Bilateral STN-DBS
n=22 Participants
Bilateral (baseline) STN-DBS settings
|
Asymmetric STN-DBS 1
n=22 Participants
50% reduction of right STN-DBS amplitude (voltage)
|
Asymmetric STN-DBS 2
n=22 Participants
50% reduction of left STN-DBS amplitude (voltage)
|
|---|---|---|---|
|
Change in Quantitative Gait Analysis (3)
Step length ratio
|
1.214 ratio
Standard Error 0.286
|
-0.011 ratio
Standard Error 0.071
|
0.002 ratio
Standard Error 0.071
|
|
Change in Quantitative Gait Analysis (3)
Step length symmetry
|
0.934 ratio
Standard Error 0.19
|
0.421 ratio
Standard Error 2.36
|
-0.420 ratio
Standard Error 2.36
|
SECONDARY outcome
Timeframe: Baseline and 3 to 4 weeks after switching to each of the DBS conditions (Bilateral, Asymmetric 1, Asymmetric 2)Population: Bilateral (baseline) values are the average of the outcome measure data obtained during the 2 bilateral (baseline) conditions: 1) at enrollment before randomization and 2) after randomization. These average values are used to compare the changes associated with the 2 asymmetric conditions.
Changes in pitch in Hertz (Hz) as measured by the Praat software.
Outcome measures
| Measure |
Bilateral STN-DBS
n=22 Participants
Bilateral (baseline) STN-DBS settings
|
Asymmetric STN-DBS 1
n=22 Participants
50% reduction of right STN-DBS amplitude (voltage)
|
Asymmetric STN-DBS 2
n=22 Participants
50% reduction of left STN-DBS amplitude (voltage)
|
|---|---|---|---|
|
Change in Quantitative Speech Analysis (1)
Pitch (minimum)
|
0.434 Hz
Standard Error 0.242
|
16.864 Hz
Standard Error 7.931
|
1.176 Hz
Standard Error 7.931
|
|
Change in Quantitative Speech Analysis (1)
Pitch (maximum)
|
0.735 Hz
Standard Error 0.071
|
-146.413 Hz
Standard Error 78.824
|
-78.213 Hz
Standard Error 78.824
|
SECONDARY outcome
Timeframe: Baseline and 3 to 4 weeks after switching to each of the DBS conditions (Bilateral, Asymmetric 1, Asymmetric 2)Population: Bilateral (baseline) values are the average of the outcome measure data obtained during the 2 bilateral (baseline) conditions: 1) at enrollment before randomization and 2) after randomization. These average values are used to compare the changes associated with the 2 asymmetric conditions.
Changes in loudness in decibels (dB) as measured by the Praat software.
Outcome measures
| Measure |
Bilateral STN-DBS
n=22 Participants
Bilateral (baseline) STN-DBS settings
|
Asymmetric STN-DBS 1
n=22 Participants
50% reduction of right STN-DBS amplitude (voltage)
|
Asymmetric STN-DBS 2
n=22 Participants
50% reduction of left STN-DBS amplitude (voltage)
|
|---|---|---|---|
|
Change in Quantitative Speech Analysis (2)
Loudness (minimum)
|
0.003 dB
Standard Error 0.048
|
0.549 dB
Standard Error 0.783
|
0.138 dB
Standard Error 0.783
|
|
Change in Quantitative Speech Analysis (2)
Loudness (maximum)
|
0.218 dB
Standard Error 0.083
|
0.619 dB
Standard Error 0.745
|
-0.003 dB
Standard Error 0.745
|
SECONDARY outcome
Timeframe: Baseline and 3 to 4 weeks after switching to each of the DBS conditions (Bilateral, Asymmetric 1, Asymmetric 2)Population: Bilateral (baseline) values are the average of the outcome measure data obtained during the 2 bilateral (baseline) conditions: 1) at enrollment before randomization and 2) after randomization. These average values are used to compare the changes associated with the 2 asymmetric conditions.
Changes in jitter measured in percentage by the Praat software. In this case, jitter is the percentage change in the stability of the frequency of speech tone (i.e. speech cycle-to-cycle frequency variation)
Outcome measures
| Measure |
Bilateral STN-DBS
n=22 Participants
Bilateral (baseline) STN-DBS settings
|
Asymmetric STN-DBS 1
n=22 Participants
50% reduction of right STN-DBS amplitude (voltage)
|
Asymmetric STN-DBS 2
n=22 Participants
50% reduction of left STN-DBS amplitude (voltage)
|
|---|---|---|---|
|
Change in Quantitative Speech Analysis (3)
|
1.263 percentage change in speech tone freq.
Standard Error 0.275
|
0.135 percentage change in speech tone freq.
Standard Error 0.155
|
0.063 percentage change in speech tone freq.
Standard Error 0.155
|
SECONDARY outcome
Timeframe: Baseline and 3 to 4 weeks after switching to each of the DBS conditions (Bilateral, Asymmetric 1, Asymmetric 2)Population: Bilateral (baseline) values are the average of the outcome measure data obtained during the 2 bilateral (baseline) conditions: 1) at enrollment before randomization and 2) after randomization. These average values are used to compare the changes associated with the 2 asymmetric conditions.
Changes in shimmer measured in percentage by the Praat software. In this case, shimmer is the percentage change in the stability of the amplitude of speech tone (i.e. speech cycle-to-cycle amplitude variation)
Outcome measures
| Measure |
Bilateral STN-DBS
n=22 Participants
Bilateral (baseline) STN-DBS settings
|
Asymmetric STN-DBS 1
n=22 Participants
50% reduction of right STN-DBS amplitude (voltage)
|
Asymmetric STN-DBS 2
n=22 Participants
50% reduction of left STN-DBS amplitude (voltage)
|
|---|---|---|---|
|
Change in Quantitative Speech Analysis (4)
|
0.630 percentage change in speech tone amplit.
Standard Error 0.144
|
-0.095 percentage change in speech tone amplit.
Standard Error 0.498
|
0.185 percentage change in speech tone amplit.
Standard Error 0.498
|
SECONDARY outcome
Timeframe: Baseline and 3 to 4 weeks after switching to each of the DBS conditions (Bilateral, Asymmetric 1, Asymmetric 2)Population: Bilateral (baseline) values are the average of the outcome measure data obtained during the 2 bilateral (baseline) conditions: 1) at enrollment before randomization and 2) after randomization. These average values are used to compare the changes associated with the 2 asymmetric conditions.
As measured by the Total Score of the 39-item Parkinson's Disease Quality of Life Questionnaire (PDQ-39). The PDQ-39 is a clinical and research tool to measure quality of life in Parkinson's disease. It has 39 questions, which patients score as never (0% of the time), occasionally (25% of the time), sometimes (50% of the time), often (75% of the time) or always (100% of the time). The PDQ-39 Total Score or Summary Index is the average of the 39 questions, expressed. The minimum score is 0% (never) and the maximum score is 100% (always). Lower scores indicate better quality of life and higher scores indicate worse quality of life.
Outcome measures
| Measure |
Bilateral STN-DBS
n=22 Participants
Bilateral (baseline) STN-DBS settings
|
Asymmetric STN-DBS 1
n=22 Participants
50% reduction of right STN-DBS amplitude (voltage)
|
Asymmetric STN-DBS 2
n=22 Participants
50% reduction of left STN-DBS amplitude (voltage)
|
|---|---|---|---|
|
Change in Quality of Life
|
0.792 units on a scale
Standard Error 0.154
|
1.701 units on a scale
Standard Error 2.506
|
-3.148 units on a scale
Standard Error 2.506
|
SECONDARY outcome
Timeframe: Baseline and 3 to 4 weeks after switching to each of the DBS conditions (Bilateral, Asymmetric 1, Asymmetric 2)Population: Two patients could not complete cognitive tasks due to language barrier.
Left brain cognitive function: Hopkins Verbal Learning Test-Revised: Total recall trials 1-3 (0-36), delayed recall (0-12); Phonemic Verbal Fluency (0-no max); Semantic Verbal Fluency (Animal cue) (0-no max); Letter 1-back and 2-back working memory tasks (0-100%). Right brain cognitive function: Brief Visual Memory Test-Revised: Total recall trials 1-3 (0-36), delayed recall (0-12); Computerized landmark line bisection (-10 to 10); Spatial 1-back and 2-back working memory tasks (0-100%). Ranges in parentheses. Line bisection: closer to 0 is more accurate. For the rest: higher values are better
Outcome measures
| Measure |
Bilateral STN-DBS
n=20 Participants
Bilateral (baseline) STN-DBS settings
|
Asymmetric STN-DBS 1
n=20 Participants
50% reduction of right STN-DBS amplitude (voltage)
|
Asymmetric STN-DBS 2
n=20 Participants
50% reduction of left STN-DBS amplitude (voltage)
|
|---|---|---|---|
|
Change in Select Cognitive Tasks
Spatial 2-Back Working Memory Task
|
0.16 units on a scale
Standard Deviation 21.92
|
-1.03 units on a scale
Standard Deviation 24.01
|
1.67 units on a scale
Standard Deviation 24.46
|
|
Change in Select Cognitive Tasks
HopkinsVerbalLearningTest-Revised: RecallTrials1-3
|
-0.30 units on a scale
Standard Deviation 3.81
|
0.50 units on a scale
Standard Deviation 3.90
|
-0.85 units on a scale
Standard Deviation 3.95
|
|
Change in Select Cognitive Tasks
HopkinsVerbal LearningTest-Revised: Delayed Recall
|
-0.45 units on a scale
Standard Deviation 2.04
|
-0.75 units on a scale
Standard Deviation 1.80
|
-1.40 units on a scale
Standard Deviation 2.48
|
|
Change in Select Cognitive Tasks
Phonemic Verbal Fluency
|
2.00 units on a scale
Standard Deviation 7.05
|
2.70 units on a scale
Standard Deviation 7.26
|
2.35 units on a scale
Standard Deviation 8.38
|
|
Change in Select Cognitive Tasks
Semantic Verbal Fluency (Animal cue)
|
0.05 units on a scale
Standard Deviation 6.16
|
0.50 units on a scale
Standard Deviation 4.41
|
0.80 units on a scale
Standard Deviation 3.79
|
|
Change in Select Cognitive Tasks
Letter 1-Back Working Memory Task
|
2.74 units on a scale
Standard Deviation 16.46
|
4.44 units on a scale
Standard Deviation 14.30
|
3.41 units on a scale
Standard Deviation 15.68
|
|
Change in Select Cognitive Tasks
Letter 2-Back Working Memory Task
|
3.06 units on a scale
Standard Deviation 17.35
|
0.95 units on a scale
Standard Deviation 18.98
|
0.71 units on a scale
Standard Deviation 16.83
|
|
Change in Select Cognitive Tasks
Brief Visual Memory Test-Revised: RecallTrials 1-3
|
3.25 units on a scale
Standard Deviation 4.55
|
3.45 units on a scale
Standard Deviation 5.40
|
2.30 units on a scale
Standard Deviation 4.40
|
|
Change in Select Cognitive Tasks
Brief Visual Memory Test-Revised: Delayed Recall
|
1.05 units on a scale
Standard Deviation 2.39
|
1.55 units on a scale
Standard Deviation 2.86
|
0.85 units on a scale
Standard Deviation 2.87
|
|
Change in Select Cognitive Tasks
Computerized landmark line bisection task
|
0.05 units on a scale
Standard Deviation 0.60
|
0.01 units on a scale
Standard Deviation 0.77
|
-0.02 units on a scale
Standard Deviation 0.88
|
|
Change in Select Cognitive Tasks
Spatial 1-Back Working Memory Task
|
-1.07 units on a scale
Standard Deviation 17.19
|
0.31 units on a scale
Standard Deviation 9.34
|
-5.63 units on a scale
Standard Deviation 14.65
|
Adverse Events
Bilateral STN-DBS (Study Phase)
Asymmetric STN-DBS 1 (Study Phase)
Asymmetric STN-DBS 2 (Study Phase)
Asymmetric STN-DBS 1 (Open Label Phase)
Asymmetric STN-DBS 2 (Open Label Phase)
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Bilateral STN-DBS (Study Phase)
n=22 participants at risk
Bilateral (baseline) STN-DBS settings (During the randomized, blinded phase)
|
Asymmetric STN-DBS 1 (Study Phase)
n=22 participants at risk
50% reduction of right STN-DBS amplitude (voltage) (During the randomized, blinded phase)
|
Asymmetric STN-DBS 2 (Study Phase)
n=22 participants at risk
50% reduction of left STN-DBS amplitude (voltage) (During the randomized, blinded phase)
|
Asymmetric STN-DBS 1 (Open Label Phase)
n=7 participants at risk
50% reduction of right STN-DBS amplitude (voltage) (During the open label phase)
|
Asymmetric STN-DBS 2 (Open Label Phase)
n=10 participants at risk
50% reduction of left STN-DBS amplitude (voltage) (During the open label phase)
|
|---|---|---|---|---|---|
|
Nervous system disorders
Treatment failure
|
0.00%
0/22 • Adverse event data were collected for 12-18 weeks (study duration per patient) plus at least 12 additional weeks for patients who opted for the open label phase after study completion.
|
13.6%
3/22 • Number of events 3 • Adverse event data were collected for 12-18 weeks (study duration per patient) plus at least 12 additional weeks for patients who opted for the open label phase after study completion.
|
4.5%
1/22 • Number of events 1 • Adverse event data were collected for 12-18 weeks (study duration per patient) plus at least 12 additional weeks for patients who opted for the open label phase after study completion.
|
14.3%
1/7 • Number of events 1 • Adverse event data were collected for 12-18 weeks (study duration per patient) plus at least 12 additional weeks for patients who opted for the open label phase after study completion.
|
20.0%
2/10 • Number of events 2 • Adverse event data were collected for 12-18 weeks (study duration per patient) plus at least 12 additional weeks for patients who opted for the open label phase after study completion.
|
|
Nervous system disorders
Increase in levodopa equivalent daily dose
|
0.00%
0/22 • Adverse event data were collected for 12-18 weeks (study duration per patient) plus at least 12 additional weeks for patients who opted for the open label phase after study completion.
|
22.7%
5/22 • Number of events 5 • Adverse event data were collected for 12-18 weeks (study duration per patient) plus at least 12 additional weeks for patients who opted for the open label phase after study completion.
|
9.1%
2/22 • Number of events 2 • Adverse event data were collected for 12-18 weeks (study duration per patient) plus at least 12 additional weeks for patients who opted for the open label phase after study completion.
|
0.00%
0/7 • Adverse event data were collected for 12-18 weeks (study duration per patient) plus at least 12 additional weeks for patients who opted for the open label phase after study completion.
|
0.00%
0/10 • Adverse event data were collected for 12-18 weeks (study duration per patient) plus at least 12 additional weeks for patients who opted for the open label phase after study completion.
|
Additional Information
Karlo J Lizarraga, MD, MS / Assistant Professor of Neurology
University of Rochester
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place