Trial Outcomes & Findings for Neural and Kinematic Features of Freezing of Gait for Adaptive Neurostimulation (NCT NCT03180515)
NCT ID: NCT03180515
Last Updated: 2019-11-21
Results Overview
Safety, tolerability and feasibility of aDBS
COMPLETED
NA
12 participants
30 min - 2 hours
2019-11-21
Participant Flow
Participant milestones
| Measure |
Activa PC+S Neurostimulator
For Aim 1, all participants participated in the same "state" - off dopaminergic medication and off deep brain stimulation (DBS), so that we could characterize the two groups (freezers and non-freezers, respectively people who experience freezing of gait and those who do not) at baseline.
For Aim 2, all participants underwent randomized presentations of OFF, 60 Hz DBS and 140 Hz DBS while completing several walking tasks. (So all participants had walking trials off stimulatoin, all had walking trials at 60 Hz DBS, all had walking trials at 140 Hz DBS).
For Aim 3, due to technological limitations and resources, only one subject completed the stepping in place task while on continuous DBS (cDBS), and completed the stepping in place task again while on adaptive DBS (aDBS).
For Aim 3, Aim 1 Arms: Freezers vs. non-freezers Aim 2 Arms: OFF vs. 60 Hz DBS vs. 140 Hz DBS Aim 3 Arms: OFF vs. cDBS vs. aDBS
|
|---|---|
|
Aim 1
STARTED
|
12
|
|
Aim 1
COMPLETED
|
12
|
|
Aim 1
NOT COMPLETED
|
0
|
|
Aim 2
STARTED
|
12
|
|
Aim 2
COMPLETED
|
12
|
|
Aim 2
NOT COMPLETED
|
0
|
|
Aim 3
STARTED
|
1
|
|
Aim 3
COMPLETED
|
1
|
|
Aim 3
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Neural and Kinematic Features of Freezing of Gait for Adaptive Neurostimulation
Baseline characteristics by cohort
| Measure |
Activa PC+S Neurostimulator
n=12 Participants
All patients
|
|---|---|
|
Age, Continuous
|
62.27 years
STANDARD_DEVIATION 7.07 • n=5 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
11 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
11 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Unified Parkinson's Disease Rating Scale III Score (OFF)
|
34.8 units on a scale
STANDARD_DEVIATION 14.8 • n=5 Participants
|
PRIMARY outcome
Timeframe: 30 min - 2 hoursPopulation: Due to limitations in technology and resources we were only able to test a single participant during the stepping in place task while on continuous DBS and while on adaptive DBS.
Safety, tolerability and feasibility of aDBS
Outcome measures
| Measure |
(OFF) Activa PC+S Neurostimulator
n=1 Participants
OFF stimulation
|
(cDBS) Activa PC+S Neurostimulator
n=1 Participants
Continuous or open-loop DBS
|
(aDBS) Activa PC+S Neurostimulator
n=1 Participants
Adaptive DBS
|
Non-Freezers (OFF Stim)
PD subjects without Freezing of Gait OFF Stimulation
|
Non-Freezers (60 Hz Stim)
PD subjects without Freezing of Gait on 60 Hz Stimulation
|
Non-Freezers (140 Hz Stim)
PD subjects without Freezing of Gait on 140 Hz Stimulation
|
|---|---|---|---|---|---|---|
|
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] Related to aDBS
|
0 Number of Treatment Emergent AEs
|
0 Number of Treatment Emergent AEs
|
0 Number of Treatment Emergent AEs
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 30 minutesPopulation: Subjects were classified as a Freezer or Non-Freezer by the clinical history of a subject's symptoms and/or if the subject displayed freezing behavior pre-operatively or during the tasks.
Subthalamic nucleus (STN) local field potentials (LFP) recordings demonstrate oscillatory neuronal activity in both the alpha (8-12 Hz) and beta (13-30 Hz) bands in the resting state in PD. Spectrograms were generated using a short-time Fourier transform, with a 1 second Hanning window and a 0.5 second overlap, creating a frequency resolution of 1 Hz. Power spectral densities were calculated using the Welch method with the same window and overlap parameters. Power was summed in the beta and alpha bands. This power can be representative of the magnitude of oscillatory activity in this frequency band occurring in this brain region.
Outcome measures
| Measure |
(OFF) Activa PC+S Neurostimulator
n=8 Participants
OFF stimulation
|
(cDBS) Activa PC+S Neurostimulator
n=4 Participants
Continuous or open-loop DBS
|
(aDBS) Activa PC+S Neurostimulator
Adaptive DBS
|
Non-Freezers (OFF Stim)
PD subjects without Freezing of Gait OFF Stimulation
|
Non-Freezers (60 Hz Stim)
PD subjects without Freezing of Gait on 60 Hz Stimulation
|
Non-Freezers (140 Hz Stim)
PD subjects without Freezing of Gait on 140 Hz Stimulation
|
|---|---|---|---|---|---|---|
|
Aim 1: Alpha Power
Stepping in Place Task
|
0.845 arbitrary units (power)
Standard Deviation 0.543
|
1.051 arbitrary units (power)
Standard Deviation 0.511
|
—
|
—
|
—
|
—
|
|
Aim 1: Alpha Power
Forward Walking
|
1.710 arbitrary units (power)
Standard Deviation 1.280
|
2.753 arbitrary units (power)
Standard Deviation 3.261
|
—
|
—
|
—
|
—
|
|
Aim 1: Alpha Power
Turning and Barrier Course
|
1.393 arbitrary units (power)
Standard Deviation 0.901
|
1.890 arbitrary units (power)
Standard Deviation 1.351
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 30 minutesPopulation: Subjects were classified as a Freezer or Non-Freezer by the clinical history of a subject's symptoms and/or if the subject displayed freezing behavior pre-operatively or during the tasks.
Subthalamic nucleus (STN) local field potentials (LFP) recordings demonstrate oscillatory neuronal activity in both the alpha (8-12 Hz) and beta (13-30 Hz) bands in the resting state in PD. Spectrograms were generated using a short-time Fourier transform, with a 1 second Hanning window and a 0.5 second overlap, creating a frequency resolution of 1 Hz. Power spectral densities were calculated using the Welch method with the same window and overlap parameters. Power was summed in the beta and alpha bands. This power can be representative of the magnitude of oscillatory activity in this frequency band occurring in this brain region.
Outcome measures
| Measure |
(OFF) Activa PC+S Neurostimulator
n=8 Participants
OFF stimulation
|
(cDBS) Activa PC+S Neurostimulator
n=4 Participants
Continuous or open-loop DBS
|
(aDBS) Activa PC+S Neurostimulator
Adaptive DBS
|
Non-Freezers (OFF Stim)
PD subjects without Freezing of Gait OFF Stimulation
|
Non-Freezers (60 Hz Stim)
PD subjects without Freezing of Gait on 60 Hz Stimulation
|
Non-Freezers (140 Hz Stim)
PD subjects without Freezing of Gait on 140 Hz Stimulation
|
|---|---|---|---|---|---|---|
|
Aim 1: Beta Power
Turning and Barrier Course
|
7.321 arbitrary units (power)
Standard Deviation 4.429
|
6.993 arbitrary units (power)
Standard Deviation 0.207
|
—
|
—
|
—
|
—
|
|
Aim 1: Beta Power
Stepping in Place Task
|
4.085 arbitrary units (power)
Standard Deviation 2.077
|
11.258 arbitrary units (power)
Standard Deviation 8.493
|
—
|
—
|
—
|
—
|
|
Aim 1: Beta Power
Forward Walking
|
9.143 arbitrary units (power)
Standard Deviation 6.835
|
8.400 arbitrary units (power)
Standard Deviation 5.529
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 30 minutesPopulation: Subjects were classified as a Freezer or Non-Freezer by the clinical history of a subject's symptoms and/or if the subject displayed freezing behavior pre-operatively or during the tasks.
The predictability of the local field potentials (band-pass filtered between 8-12 Hz for alpha) was analyzed using Sample Entropy (SampEn), a nonlinear measure suitable for physiological time series. SampEn may be a more consistent measure and more suitable to shorter time series data than approximate entropy, partially due to the elimination of counting self matches. SampEn is calculated as the negative logarithm of the estimated conditional probability that if consecutive subseries of length m are similar according to some preset tolerance r, the consecutive subseries of length m+1 will be similar too. Here the length of the vector pairs, m, denotes the embedding dimension.
Outcome measures
| Measure |
(OFF) Activa PC+S Neurostimulator
n=8 Participants
OFF stimulation
|
(cDBS) Activa PC+S Neurostimulator
n=4 Participants
Continuous or open-loop DBS
|
(aDBS) Activa PC+S Neurostimulator
Adaptive DBS
|
Non-Freezers (OFF Stim)
PD subjects without Freezing of Gait OFF Stimulation
|
Non-Freezers (60 Hz Stim)
PD subjects without Freezing of Gait on 60 Hz Stimulation
|
Non-Freezers (140 Hz Stim)
PD subjects without Freezing of Gait on 140 Hz Stimulation
|
|---|---|---|---|---|---|---|
|
Aim 1: Alpha Sample Entropy
Stepping in Place Task
|
0.251 arbitrary units
Standard Deviation 0.002
|
0.253 arbitrary units
Standard Deviation 0.004
|
—
|
—
|
—
|
—
|
|
Aim 1: Alpha Sample Entropy
Forward Walking
|
0.248 arbitrary units
Standard Deviation 0.007
|
0.247 arbitrary units
Standard Deviation 0.007
|
—
|
—
|
—
|
—
|
|
Aim 1: Alpha Sample Entropy
Turning and Barrier Course
|
0.253 arbitrary units
Standard Deviation 0.003
|
0.250 arbitrary units
Standard Deviation 0.004
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 30 minutesPopulation: Subjects were classified as a Freezer or Non-Freezer by the clinical history of a subject's symptoms and/or if the subject displayed freezing behavior pre-operatively or during the tasks.
The predictability of the local field potentials (band-pass filtered between 15-30 Hz for beta) was analyzed using Sample Entropy (SampEn), a nonlinear measure suitable for physiological time series. SampEn may be a more consistent measure and more suitable to shorter time series data than approximate entropy, partially due to the elimination of counting self matches. SampEn is calculated as the negative logarithm of the estimated conditional probability that if consecutive subseries of length m are similar according to some preset tolerance r, the consecutive subseries of length m+1 will be similar too. Here the length of the vector pairs, m, denotes the embedding dimension.
Outcome measures
| Measure |
(OFF) Activa PC+S Neurostimulator
n=8 Participants
OFF stimulation
|
(cDBS) Activa PC+S Neurostimulator
n=4 Participants
Continuous or open-loop DBS
|
(aDBS) Activa PC+S Neurostimulator
Adaptive DBS
|
Non-Freezers (OFF Stim)
PD subjects without Freezing of Gait OFF Stimulation
|
Non-Freezers (60 Hz Stim)
PD subjects without Freezing of Gait on 60 Hz Stimulation
|
Non-Freezers (140 Hz Stim)
PD subjects without Freezing of Gait on 140 Hz Stimulation
|
|---|---|---|---|---|---|---|
|
Aim 1: Beta Sample Entropy
Stepping in Place Task
|
0.407 arbitrary units
Standard Deviation 0.031
|
0.337 arbitrary units
Standard Deviation 0.062
|
—
|
—
|
—
|
—
|
|
Aim 1: Beta Sample Entropy
Forward Walking
|
0.380 arbitrary units
Standard Deviation 0.050
|
0.376 arbitrary units
Standard Deviation 0.053
|
—
|
—
|
—
|
—
|
|
Aim 1: Beta Sample Entropy
Turning and Barrier Course
|
0.377 arbitrary units
Standard Deviation 0.050
|
0.376 arbitrary units
Standard Deviation 0.052
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 30 minutesPopulation: 12 participants total: the 8 freezers are the same participants across stimulation conditions; the 4 non-freezers are the same participants across stimulation conditions. Subjects were classified Freezer/Non-Freezer by the clinical history of a subject's symptoms and/or if the subject displayed freezing behavior pre-operatively or during the tasks.
Asymmetry during both forward walking and stepping in place was calculated using periods of walking or stepping when the subject was not freezing. According to previous studies, asymmetry is defined as: 100\*(absolute value of the natural log of the shorter average swing time over the longer average swing time) or mathematically: 100\*\| ln (SSWT/LSWT) \| where SSWT = shorter mean swing time LSWT = longer mean swing time
Outcome measures
| Measure |
(OFF) Activa PC+S Neurostimulator
n=8 Participants
OFF stimulation
|
(cDBS) Activa PC+S Neurostimulator
n=8 Participants
Continuous or open-loop DBS
|
(aDBS) Activa PC+S Neurostimulator
n=8 Participants
Adaptive DBS
|
Non-Freezers (OFF Stim)
n=4 Participants
PD subjects without Freezing of Gait OFF Stimulation
|
Non-Freezers (60 Hz Stim)
n=4 Participants
PD subjects without Freezing of Gait on 60 Hz Stimulation
|
Non-Freezers (140 Hz Stim)
n=4 Participants
PD subjects without Freezing of Gait on 140 Hz Stimulation
|
|---|---|---|---|---|---|---|
|
Aim 2: Asymmetry
Stepping in Place Task
|
26.74 asymmetry (%)
Standard Deviation 23.44
|
27.1 asymmetry (%)
Standard Deviation 21.42
|
15.99 asymmetry (%)
Standard Deviation 12.12
|
9.54 asymmetry (%)
Standard Deviation 6.87
|
7.86 asymmetry (%)
Standard Deviation 7.10
|
7.25 asymmetry (%)
Standard Deviation 9.03
|
|
Aim 2: Asymmetry
Forward Walking
|
6.11 asymmetry (%)
Standard Deviation 4.11
|
5.01 asymmetry (%)
Standard Deviation 2.97
|
4.52 asymmetry (%)
Standard Deviation 3.39
|
3.32 asymmetry (%)
Standard Deviation 1.88
|
2.41 asymmetry (%)
Standard Deviation 2.50
|
4.50 asymmetry (%)
Standard Deviation 2.23
|
SECONDARY outcome
Timeframe: 30 minutesPopulation: 12 participants total: the 8 freezers are the same participants across stimulation conditions; the 4 non-freezers are the same participants across stimulation conditions.
Arrhythmicity during both forward walking and stepping in place was calculated using periods of walking or stepping when the subject was not freezing. According to previous studies, arrhythmicity is defined as the mean stride time coefficient of variation of both legs, and a greater stride time CV implies less rhythmic gait or stepping. Higher arrhythmicity corresponds to more arrhythmic, or more impaired, gait.
Outcome measures
| Measure |
(OFF) Activa PC+S Neurostimulator
n=8 Participants
OFF stimulation
|
(cDBS) Activa PC+S Neurostimulator
n=8 Participants
Continuous or open-loop DBS
|
(aDBS) Activa PC+S Neurostimulator
n=8 Participants
Adaptive DBS
|
Non-Freezers (OFF Stim)
n=4 Participants
PD subjects without Freezing of Gait OFF Stimulation
|
Non-Freezers (60 Hz Stim)
n=4 Participants
PD subjects without Freezing of Gait on 60 Hz Stimulation
|
Non-Freezers (140 Hz Stim)
n=4 Participants
PD subjects without Freezing of Gait on 140 Hz Stimulation
|
|---|---|---|---|---|---|---|
|
Aim 2: Arrhythmicity
Forward Walking
|
6.76 arrythmicity (CV%)
Standard Deviation 3.29
|
5.18 arrythmicity (CV%)
Standard Deviation 2.25
|
6.41 arrythmicity (CV%)
Standard Deviation 2.68
|
5.98 arrythmicity (CV%)
Standard Deviation 4.37
|
4.96 arrythmicity (CV%)
Standard Deviation 1.35
|
4.94 arrythmicity (CV%)
Standard Deviation 1.38
|
|
Aim 2: Arrhythmicity
Stepping in Place Task
|
54.04 arrythmicity (CV%)
Standard Deviation 50.46
|
27.49 arrythmicity (CV%)
Standard Deviation 33.23
|
29.34 arrythmicity (CV%)
Standard Deviation 56.18
|
4.01 arrythmicity (CV%)
Standard Deviation 0.81
|
4.10 arrythmicity (CV%)
Standard Deviation 1.40
|
4.00 arrythmicity (CV%)
Standard Deviation 0.73
|
SECONDARY outcome
Timeframe: 30 minutesPopulation: 12 participants total: the 8 freezers are the same participants across stimulation conditions; the 4 non-freezers are the same participants across stimulation conditions.
Kinematic Features associated with Freezing of Gait
Outcome measures
| Measure |
(OFF) Activa PC+S Neurostimulator
n=8 Participants
OFF stimulation
|
(cDBS) Activa PC+S Neurostimulator
n=8 Participants
Continuous or open-loop DBS
|
(aDBS) Activa PC+S Neurostimulator
n=8 Participants
Adaptive DBS
|
Non-Freezers (OFF Stim)
n=4 Participants
PD subjects without Freezing of Gait OFF Stimulation
|
Non-Freezers (60 Hz Stim)
n=4 Participants
PD subjects without Freezing of Gait on 60 Hz Stimulation
|
Non-Freezers (140 Hz Stim)
n=4 Participants
PD subjects without Freezing of Gait on 140 Hz Stimulation
|
|---|---|---|---|---|---|---|
|
Aim 2: Stride Time
Stepping in Place Task
|
1.71 seconds
Standard Deviation 0.68
|
1.44 seconds
Standard Deviation 0.53
|
1.21 seconds
Standard Deviation 0.44
|
1.07 seconds
Standard Deviation 0.15
|
1.05 seconds
Standard Deviation 0.14
|
1.06 seconds
Standard Deviation 0.17
|
|
Aim 2: Stride Time
Forward Walking
|
1.14 seconds
Standard Deviation 0.19
|
1.11 seconds
Standard Deviation 0.15
|
1.10 seconds
Standard Deviation 0.14
|
1.16 seconds
Standard Deviation 0.06
|
1.15 seconds
Standard Deviation 0.07
|
1.18 seconds
Standard Deviation 0.10
|
SECONDARY outcome
Timeframe: 30 minutesPopulation: 12 participants total: the 8 freezers are the same participants across stimulation conditions; the 4 non-freezers are the same participants across stimulation conditions.
Freezing of gait episodes during stepping in place were identified using a validated computerized algorithm, and during forward walking by a blinded rater. The percent time freezing was calculated by dividing the time spent freezing by the total time to complete the task then multiplying by 100 to get a percent. If no freezing was observed, then the percent time freezing reported was 0.0%.
Outcome measures
| Measure |
(OFF) Activa PC+S Neurostimulator
n=8 Participants
OFF stimulation
|
(cDBS) Activa PC+S Neurostimulator
n=8 Participants
Continuous or open-loop DBS
|
(aDBS) Activa PC+S Neurostimulator
n=8 Participants
Adaptive DBS
|
Non-Freezers (OFF Stim)
n=4 Participants
PD subjects without Freezing of Gait OFF Stimulation
|
Non-Freezers (60 Hz Stim)
n=4 Participants
PD subjects without Freezing of Gait on 60 Hz Stimulation
|
Non-Freezers (140 Hz Stim)
n=4 Participants
PD subjects without Freezing of Gait on 140 Hz Stimulation
|
|---|---|---|---|---|---|---|
|
Aim 2: Percent Time Freezing
Stepping in Place Task
|
29.37 % time freezing
Standard Deviation 38.27
|
11.01 % time freezing
Standard Deviation 29.57
|
18.13 % time freezing
Standard Deviation 34.58
|
0.0 % time freezing
Standard Deviation 0.0
|
0.0 % time freezing
Standard Deviation 0.0
|
0.0 % time freezing
Standard Deviation 0.0
|
|
Aim 2: Percent Time Freezing
Forward Walking
|
0.17 % time freezing
Standard Deviation 0.48
|
0.0 % time freezing
Standard Deviation 0.0
|
0.0 % time freezing
Standard Deviation 0.0
|
0.0 % time freezing
Standard Deviation 0.0
|
0.0 % time freezing
Standard Deviation 0.0
|
0.0 % time freezing
Standard Deviation 0.0
|
SECONDARY outcome
Timeframe: 30 minutesPopulation: Due to limitations in technology and resources we were only able to test a single participant during the stepping in place task while on continuous DBS and while on adaptive DBS.
Freezing of gait episodes during stepping in place were identified using a validated computerized algorithm. The percent time freezing was calculated by dividing the time spent freezing by the total time to complete the task then multiplying by 100 to get a percent. If no freezing was observed, then the percent time freezing reported was 0.0%. The percent time spent freezing was compared while the participant was doing the stepping in place task on continuous deep brain stimulation (cDBS) and while the participant was doing the stepping in place task on adaptive deep brain stimulation (aDBS).
Outcome measures
| Measure |
(OFF) Activa PC+S Neurostimulator
n=1 Participants
OFF stimulation
|
(cDBS) Activa PC+S Neurostimulator
n=1 Participants
Continuous or open-loop DBS
|
(aDBS) Activa PC+S Neurostimulator
n=1 Participants
Adaptive DBS
|
Non-Freezers (OFF Stim)
PD subjects without Freezing of Gait OFF Stimulation
|
Non-Freezers (60 Hz Stim)
PD subjects without Freezing of Gait on 60 Hz Stimulation
|
Non-Freezers (140 Hz Stim)
PD subjects without Freezing of Gait on 140 Hz Stimulation
|
|---|---|---|---|---|---|---|
|
Percent Time Freezing
|
44 % time freezing
Standard Deviation 0
|
2 % time freezing
Standard Deviation 0
|
0 % time freezing
Standard Deviation 0
|
—
|
—
|
—
|
Adverse Events
Activa PC+S Neurostimulator Aim 1
Activa PC +S Neurostimulator Aim 2
Activa PC +S Neurostimulator Aim 3
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place