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Continuous deep brain stimulation (cDBS) is an established therapy for the major motor signs in Parkinson's disease, however some patients find that it does not adequately treat their freezing of gait (FOG). Currently, cDBS is limited to "open-loop" stimulation,without real-time adjustment to the patient's state of activity, fluctuations and types of motor symptoms, medication dosages, or neural markers of the disease. The purpose of this study is to determine if an adaptive DBS system,responding to patient specific, clinically relevant neural or kinematic feedback related to FOG, is more effective than continuous DBS on the motor Unified Parkinson's Disease Rating Scale (UPDRS III) and gait measures of PD.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Activa PC+S Neurostimulator | Experimental | All patients will complete motor testing on both continuous DBS and adaptive DBS during a study visit. The UPDRS rater and the patient will be blind to which type of stimulation they are on. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Activa PC+S Neurostimulator | Device | Activa PC+S Neurostimulator is approved for both aDBS and cDBS paradigms. |
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| Measure | Description | Time Frame |
|---|---|---|
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] Related to aDBS | Safety, tolerability and feasibility of aDBS | 30 min - 2 hours |
| Measure | Description | Time Frame |
|---|---|---|
| Aim 1: Alpha Power | 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Helen Bronte-Stewart, MS, MD | Stanford University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Stanford Movement Disorders | Palo Alto | California | 94304 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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 |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Aim 1 |
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| Aim 2 |
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| Aim 3 |
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| ID | Title | Description |
|---|---|---|
| BG000 | Activa PC+S Neurostimulator | All patients |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] Related to aDBS | Safety, tolerability and feasibility of aDBS | 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. | Posted | Number | Number of Treatment Emergent AEs | 30 min - 2 hours |
|
2 days - throughout the entirety of the research visit
No AE's reported. We used an adverse events questionnaire to assess whether patients felt any of the following: pins and needles, tightness in arm or face, light headedness, nausea, speech problems, confusion/cognitive changes, unwanted mood changes, balance problems, other symtpoms/notes.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Activa PC+S Neurostimulator Aim 1 | Aim 1 Arms: Freezers vs. non-freezers All participants participated in Aim 1 |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Bronte-Stewart Lab | Stanford School of Medicine | 6507236709 | hbsmovlab@gmail.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| SAP | No | Yes | No | Statistical Analysis Plan | Sep 4, 2018 | Sep 5, 2019 | SAP_000.pdf |
| Prot | Yes | No | No | Study Protocol | Nov 20, 2018 | Sep 5, 2019 | Prot_001.pdf |
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| ID | Term |
|---|---|
| D010300 | Parkinson Disease |
| ID | Term |
|---|---|
| D020734 | Parkinsonian Disorders |
| D001480 | Basal Ganglia Diseases |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
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| 30 minutes |
| Aim 1: Beta Power | 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. | 30 minutes |
| Aim 1: Alpha Sample Entropy | 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. | 30 minutes |
| Aim 1: Beta Sample Entropy | 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. | 30 minutes |
| Aim 2: Asymmetry | 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 | 30 minutes |
| Aim 2: Arrhythmicity | 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. | 30 minutes |
| Aim 2: Stride Time | Kinematic Features associated with Freezing of Gait | 30 minutes |
| Aim 2: Percent Time Freezing | 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%. | 30 minutes |
| Percent Time Freezing | 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). | 30 minutes |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
|
| Unified Parkinson's Disease Rating Scale III Score (OFF) | The Unified Parkinson's Disease Rating Scale or UPDRS Part III is the motor examination of the standard clinical rating scale used to gauge the course of Parkinson's disease in patients. Total score is reported as the sum of the subscores, and higher values indicate greater disease severity. The range for the total score of the UPDRS III Motor Examination is between 0-108. | Mean | Standard Deviation | units on a scale |
|
| (aDBS) Activa PC+S Neurostimulator |
Adaptive DBS |
|
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| Secondary | Aim 1: Alpha Power | 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. | 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. | Posted | Mean | Standard Deviation | arbitrary units (power) | 30 minutes |
|
|
|
| Secondary | Aim 1: Beta Power | 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. | 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. | Posted | Mean | Standard Deviation | arbitrary units (power) | 30 minutes |
|
|
|
| Secondary | Aim 1: Alpha Sample Entropy | 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. | 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. | Posted | Mean | Standard Deviation | arbitrary units | 30 minutes |
|
|
|
| Secondary | Aim 1: Beta Sample Entropy | 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. | 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. | Posted | Mean | Standard Deviation | arbitrary units | 30 minutes |
|
|
|
| Secondary | Aim 2: Asymmetry | 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 | 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. | Posted | Mean | Standard Deviation | asymmetry (%) | 30 minutes |
|
|
|
| Secondary | Aim 2: Arrhythmicity | 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. | 12 participants total: the 8 freezers are the same participants across stimulation conditions; the 4 non-freezers are the same participants across stimulation conditions. | Posted | Mean | Standard Deviation | arrythmicity (CV%) | 30 minutes |
|
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| Secondary | Aim 2: Stride Time | Kinematic Features associated with Freezing of Gait | 12 participants total: the 8 freezers are the same participants across stimulation conditions; the 4 non-freezers are the same participants across stimulation conditions. | Posted | Mean | Standard Deviation | seconds | 30 minutes |
|
|
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| Secondary | Aim 2: Percent Time Freezing | 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%. | 12 participants total: the 8 freezers are the same participants across stimulation conditions; the 4 non-freezers are the same participants across stimulation conditions. | Posted | Mean | Standard Deviation | % time freezing | 30 minutes |
|
|
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| Secondary | Percent Time Freezing | 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). | 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. | Posted | Mean | Standard Deviation | % time freezing | 30 minutes |
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| 0 |
| 12 |
| 0 |
| 12 |
| 0 |
| 12 |
| EG001 | Activa PC +S Neurostimulator Aim 2 | Aim 2 Arms: OFF vs. 60 Hz DBS vs. 140 Hz DBS All participants participated in Aim 2. Within participant, adverse effects were assessed between OFF DBS, 60 Hz DBS and 140 Hz DBS. | 0 | 12 | 0 | 12 | 0 | 12 |
| EG002 | Activa PC +S Neurostimulator Aim 3 | Aim 3 Arms: OFF vs. cDBS vs. aDBS Due to limitations in technology and resources, only one participant participated in Aim 3. Within participant, adverse effects were assessed between OFF DBS, cDBS, and aDBS. | 0 | 1 | 0 | 1 | 0 | 1 |
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| D009422 | Nervous System Diseases |
| D009069 | Movement Disorders |
| D000080874 | Synucleinopathies |
| D019636 | Neurodegenerative Diseases |
| Turning and Barrier Course |
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| Turning and Barrier Course |
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| Turning and Barrier Course |
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| Turning and Barrier Course |
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| Forward Walking |
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| Forward Walking |
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| Forward Walking |
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| Forward Walking |
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