Parkinson Disease
Conditions
Keywords
Deep Brain Stimulation, Parkinson's Disease, Wearable Sensors
Brief summary
The objective of this study is to further the understanding and application of 60Hz subthalamic deep brain stimulation (STN-DBS) in Parkinson's patients with gait disorder. The investigators will achieve this through 2 study aims: 1. Determine the impact of 60Hz subthalamic deep brain stimulation on gait kinematics using wearable sensors 2. Develop machine learning models to predict optimal subthalamic deep brain stimulation frequency based on wearable sensors
Detailed description
Gait disorder, which manifests as shuffling, reduction in speed, multistep turning, and/or freezing of gait (FOG), can arise later in the Parkinson's disease (PD) course and cause significant disability. Ultimately, patients are at risk for falls and can become socially isolated due to their mobility limitations. These symptoms tend not to respond to high frequency STN-DBS. However, lower frequency stimulation (60-80Hz) of the STN in treating gait disorder and/or freezing of gait has demonstrated benefit. This study potentially can expand knowledge of 60hz DBS while improving its utilization in combination with PD medications-enabling sustainable and possibly predictable therapeutic benefit.
Interventions
DEVICEDeep Brain Stimulation
Each DBS electrode contact will be reprogrammed in 60hz and High Frequency Stimulation (180hz) in the Levodopa ON (medicated) and OFF (unmedicated) conditions.
Sponsors
National Institute of Neurological Disorders and Stroke (NINDS)
The University of Tennessee, Knoxville
Northwell Health
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female, aged 21-80 2. Patients diagnosed with Parkinson's disease (PD) 3. PD subjects who have bilateral STN-DBS (greater than 3 months) or in the preoperative stage of being implanted with bilateral STN-DBS 4. Have underlying gait disorder 5. Currently treated with oral levodopa therapy 6. Willingness to comply with all study procedures
Exclusion criteria
1. Cognitive deficits based on historical record that limit participant compliance with study protocol 2. Vestibular disorder or musculoskeletal problems affecting gait or balance
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Gait Kinematic Response for 180 and 60Hz DBS | 1-2 minute period with each stimulation condition in the Medicated and Unmedicated states. | The measurements of interest were captured during the instrumented walk. Interaction of DBS Frequency and Levodopa on gait kinematics was assessed using LM-ANOVA. |
| Accuracy of Discriminating STN-DBS (60hz vs. High Frequency) and Medication States With Machine Learning(ML) | 2 years | We apply ML techniques to a data set of gait kinematics acquired from instrumented walking assessments and utilize random forest ML algorithms to identify participants' stimulation frequency/medication condition. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Hand Tremor Severity for 180 and 60Hz DBS | 1 minute test session for each stimulation condition | The difference in tremor (e.g. rest, postural) severity will be measured with the kinesia sensor for each DBS electrode stimulation pair (60hz or High Frequency) in both the medicated and unmedicated states on a severity scale from 0-4. Higher number = worse outcome |
| Change in Speed of Limb Movements for 180 and 60Hz DBS | 1 minute test session for each stimulation condition | The difference in the speed of limb movements (e.g. hand grasps and leg lifts) will be measured with the kinesia sensor for each DBS electrode stimulation pair (60hz or High Frequency) in both the medicated and unmedicated states on a severity scale of 0-4. Higher values = worse outcome. |
Countries
United States
Participant flow
Recruitment details
All Subjects were recruited through the Movement Disorders Center at Northwell Health, NY.
Participants by arm
| Arm | Count |
|---|---|
| Deep Brain Stimulation(DBS) OFF & ON Medication Subthalamic-DBS in the Levodopa OFF and ON state.
Deep Brain Stimulation: Each DBS electrode contact will be reprogrammed in 60hz and High Frequency Stimulation (180hz) in the OFF (unmedicated) and ON (medicated) conditions. | 22 |
| Total | 22 |
Baseline characteristics
| Characteristic | Deep Brain Stimulation(DBS) OFF & ON Medication |
|---|---|
| Age, Continuous | 63.6 years STANDARD_DEVIATION 9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 17 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| PD Phenotype Intermediate | 12 Participants |
| PD Phenotype Postural Instability and Gait Disorder(PIGD) | 6 Participants |
| PD Phenotype Tremor Dominant | 4 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 21 Participants |
| Region of Enrollment United States | 22 participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 16 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 | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 24 | 0 / 24 | 0 / 24 | 0 / 24 | 0 / 24 | 0 / 24 |
| other Total, other adverse events | 0 / 24 | 0 / 24 | 0 / 24 | 0 / 24 | 0 / 24 | 0 / 24 |
| serious Total, serious adverse events | 0 / 24 | 0 / 24 | 0 / 24 | 0 / 24 | 0 / 24 | 0 / 24 |
Outcome results
Primary
Accuracy of Discriminating STN-DBS (60hz vs. High Frequency) and Medication States With Machine Learning(ML)
We apply ML techniques to a data set of gait kinematics acquired from instrumented walking assessments and utilize random forest ML algorithms to identify participants' stimulation frequency/medication condition.
Time frame: 2 years
Population: The random forest classifier's predictive accuracy for discriminating OFF DBS/OFF MED condition from alternative DBS/MED conditions is listed below.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 180HZ (OFF MED) | Accuracy of Discriminating STN-DBS (60hz vs. High Frequency) and Medication States With Machine Learning(ML) | 64 percentage of random forest accuracy |
Primary
Gait Kinematic Response for 180 and 60Hz DBS
The measurements of interest were captured during the instrumented walk. Interaction of DBS Frequency and Levodopa on gait kinematics was assessed using LM-ANOVA.
Time frame: 1-2 minute period with each stimulation condition in the Medicated and Unmedicated states.
Population: Scale range 0-100 ( toe angle - higher value is a better outcome; Single limb support - higher value is better outcome; left foot stance % - higher value is worse outcome; left foot swing - higher value is better outcome; left arm range of motion - higher value is better outcome)
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 180HZ (OFF MED) | Gait Kinematic Response for 180 and 60Hz DBS | Left Foot Swing | 35.77 units on a scale | Standard Error 0.55 |
| 180HZ (OFF MED) | Gait Kinematic Response for 180 and 60Hz DBS | Right Single Limb Support | 35.77 units on a scale | Standard Error 0.56 |
| 180HZ (OFF MED) | Gait Kinematic Response for 180 and 60Hz DBS | Left Arm Range of Motion | 19.13 units on a scale | Standard Error 1.94 |
| 180HZ (OFF MED) | Gait Kinematic Response for 180 and 60Hz DBS | Left Foot Stance | 64.23 units on a scale | Standard Error 0.55 |
| 180HZ (OFF MED) | Gait Kinematic Response for 180 and 60Hz DBS | Right Toe off Angle | 27.37 units on a scale | Standard Error 1.08 |
| 180Hz (ON Med) | Gait Kinematic Response for 180 and 60Hz DBS | Left Foot Stance | 63.48 units on a scale | Standard Error 0.56 |
| 180Hz (ON Med) | Gait Kinematic Response for 180 and 60Hz DBS | Left Foot Swing | 36.52 units on a scale | Standard Error 0.56 |
| 180Hz (ON Med) | Gait Kinematic Response for 180 and 60Hz DBS | Left Arm Range of Motion | 25.37 units on a scale | Standard Error 1.99 |
| 180Hz (ON Med) | Gait Kinematic Response for 180 and 60Hz DBS | Right Single Limb Support | 36.44 units on a scale | Standard Error 0.56 |
| 180Hz (ON Med) | Gait Kinematic Response for 180 and 60Hz DBS | Right Toe off Angle | 29.05 units on a scale | Standard Error 1.09 |
| 60Hz (OFF Med) | Gait Kinematic Response for 180 and 60Hz DBS | Left Foot Stance | 64.94 units on a scale | Standard Error 0.55 |
| 60Hz (OFF Med) | Gait Kinematic Response for 180 and 60Hz DBS | Right Toe off Angle | 25.68 units on a scale | Standard Error 1.08 |
| 60Hz (OFF Med) | Gait Kinematic Response for 180 and 60Hz DBS | Right Single Limb Support | 35.10 units on a scale | Standard Error 0.56 |
| 60Hz (OFF Med) | Gait Kinematic Response for 180 and 60Hz DBS | Left Foot Swing | 35.07 units on a scale | Standard Error 0.55 |
| 60Hz (OFF Med) | Gait Kinematic Response for 180 and 60Hz DBS | Left Arm Range of Motion | 17.98 units on a scale | Standard Error 1.95 |
| 60Hz (ON MED) | Gait Kinematic Response for 180 and 60Hz DBS | Left Foot Swing | 36.48 units on a scale | Standard Error 0.56 |
| 60Hz (ON MED) | Gait Kinematic Response for 180 and 60Hz DBS | Right Single Limb Support | 36.47 units on a scale | Standard Error 0.56 |
| 60Hz (ON MED) | Gait Kinematic Response for 180 and 60Hz DBS | Right Toe off Angle | 28.31 units on a scale | Standard Error 1.09 |
| 60Hz (ON MED) | Gait Kinematic Response for 180 and 60Hz DBS | Left Foot Stance | 63.52 units on a scale | Standard Error 0.56 |
| 60Hz (ON MED) | Gait Kinematic Response for 180 and 60Hz DBS | Left Arm Range of Motion | 20.48 units on a scale | Standard Error 1.98 |
p-value: <0.05Mixed Models Analysis
Secondary
Change in Hand Tremor Severity for 180 and 60Hz DBS
The difference in tremor (e.g. rest, postural) severity will be measured with the kinesia sensor for each DBS electrode stimulation pair (60hz or High Frequency) in both the medicated and unmedicated states on a severity scale from 0-4. Higher number = worse outcome
Time frame: 1 minute test session for each stimulation condition
Population: There was significant difference between rest and postural tremor between 60Hz and 180hz
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 180HZ (OFF MED) | Change in Hand Tremor Severity for 180 and 60Hz DBS | Right Hand Postural Tremor | 0.22 score on a scale | Standard Error 0.09 |
| 180HZ (OFF MED) | Change in Hand Tremor Severity for 180 and 60Hz DBS | Left Hand Postural Tremor | 0.23 score on a scale | Standard Error 0.09 |
| 180HZ (OFF MED) | Change in Hand Tremor Severity for 180 and 60Hz DBS | Left Rest Tremor | 0.19 score on a scale | Standard Error 0.08 |
| 180HZ (OFF MED) | Change in Hand Tremor Severity for 180 and 60Hz DBS | Right Hand Rest Tremor | 0.27 score on a scale | Standard Error 0.12 |
| 180Hz (ON Med) | Change in Hand Tremor Severity for 180 and 60Hz DBS | Left Hand Postural Tremor | 0.13 score on a scale | Standard Error 0.09 |
| 180Hz (ON Med) | Change in Hand Tremor Severity for 180 and 60Hz DBS | Right Hand Rest Tremor | 0.23 score on a scale | Standard Error 0.11 |
| 180Hz (ON Med) | Change in Hand Tremor Severity for 180 and 60Hz DBS | Left Rest Tremor | 0.19 score on a scale | Standard Error 0.08 |
| 180Hz (ON Med) | Change in Hand Tremor Severity for 180 and 60Hz DBS | Right Hand Postural Tremor | 0.16 score on a scale | Standard Error 0.1 |
| 60Hz (OFF Med) | Change in Hand Tremor Severity for 180 and 60Hz DBS | Left Rest Tremor | 0.51 score on a scale | Standard Error 0.08 |
| 60Hz (OFF Med) | Change in Hand Tremor Severity for 180 and 60Hz DBS | Left Hand Postural Tremor | 0.66 score on a scale | Standard Error 0.09 |
| 60Hz (OFF Med) | Change in Hand Tremor Severity for 180 and 60Hz DBS | Right Hand Rest Tremor | 0.57 score on a scale | Standard Error 0.12 |
| 60Hz (OFF Med) | Change in Hand Tremor Severity for 180 and 60Hz DBS | Right Hand Postural Tremor | 0.58 score on a scale | Standard Error 0.1 |
| 60Hz (ON MED) | Change in Hand Tremor Severity for 180 and 60Hz DBS | Left Hand Postural Tremor | 0.46 score on a scale | Standard Error 0.09 |
| 60Hz (ON MED) | Change in Hand Tremor Severity for 180 and 60Hz DBS | Left Rest Tremor | 0.40 score on a scale | Standard Error 0.08 |
| 60Hz (ON MED) | Change in Hand Tremor Severity for 180 and 60Hz DBS | Right Hand Postural Tremor | 0.42 score on a scale | Standard Error 0.1 |
| 60Hz (ON MED) | Change in Hand Tremor Severity for 180 and 60Hz DBS | Right Hand Rest Tremor | 0.45 score on a scale | Standard Error 0.11 |
Secondary
Change in Speed of Limb Movements for 180 and 60Hz DBS
The difference in the speed of limb movements (e.g. hand grasps and leg lifts) will be measured with the kinesia sensor for each DBS electrode stimulation pair (60hz or High Frequency) in both the medicated and unmedicated states on a severity scale of 0-4. Higher values = worse outcome.
Time frame: 1 minute test session for each stimulation condition
Population: There were no significant difference between groups
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 180HZ (OFF MED) | Change in Speed of Limb Movements for 180 and 60Hz DBS | Left Hand Movement Speed | 2.65 score on a scale | Standard Error 0.11 |
| 180HZ (OFF MED) | Change in Speed of Limb Movements for 180 and 60Hz DBS | Right Hand Movement Speed | 2.85 score on a scale | Standard Error 0.11 |
| 180Hz (ON Med) | Change in Speed of Limb Movements for 180 and 60Hz DBS | Right Hand Movement Speed | 2.70 score on a scale | Standard Error 0.11 |
| 180Hz (ON Med) | Change in Speed of Limb Movements for 180 and 60Hz DBS | Left Hand Movement Speed | 2.55 score on a scale | Standard Error 0.11 |
| 60Hz (OFF Med) | Change in Speed of Limb Movements for 180 and 60Hz DBS | Left Hand Movement Speed | 2.76 score on a scale | Standard Error 0.11 |
| 60Hz (OFF Med) | Change in Speed of Limb Movements for 180 and 60Hz DBS | Right Hand Movement Speed | 2.90 score on a scale | Standard Error 0.11 |
| 60Hz (ON MED) | Change in Speed of Limb Movements for 180 and 60Hz DBS | Left Hand Movement Speed | 2.58 score on a scale | Standard Error 0.11 |
| 60Hz (ON MED) | Change in Speed of Limb Movements for 180 and 60Hz DBS | Right Hand Movement Speed | 2.73 score on a scale | Standard Error 0.11 |