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Continuous deep brain stimulation (cDBS) is an established therapy for the major motor signs in Parkinson's disease. 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, is efficacious on the motor Unified Parkinson's Disease Rating Scale (UPDRS III) and specific phenotypic measures in Parkinson's Disease compared to OFF therapy (i.e., OFF DBS and withdrawn from medication) and more efficient than cDBS. Not every recruited participant completed every part of the protocol.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Activa PC+S Neurostimulator | Experimental | Participants will be own controls and undergo both adaptive and continuous deep brain stimulation testing paradigms using Nexus D research tool PC+S: Primary Cell+Sensing |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Adaptive DBS (Activa PC+S Neurostimulator) | Device |
|
| |
| Measure | Description | Time Frame |
|---|---|---|
| Normalized Beta Band Power (13-30 Hz) During aDBS | Beta Band Power will be recorded continuously during intervention (30 minutes). The PC+S streams off power of the local field potential signal measured from the subthalamic nucleus in a frequency band of interest within the beta band (13-30 Hz). The amplitude of the signal, beta power, was streamed from each subthalamic nucleus (STN) during the calibration period of the experiment when DBS was off (i.e., OFF therapy), when continuous DBS was set at the lower and upper stimulation voltage that were found for determining the stimulation limits of adaptive DBS, and during the 30 minutes of aDBS. We calculated the median observed beta power during aDBS. To compute normalized beta band power, the median value was divided by the observed beta power OFF therapy and during the continuous DBS at the lower and upper voltage. A value less than 1 indicates reduced beta power during aDBS compared to the other conditions. | 30 minutes |
| Change in UPDRS III Score | Movement Disorder Society's Unified Parkinson's Disease Rating Scale III (UPDRS III) score will be measured after 30 minutes of intervention and compared to baseline. Scores on the UPDRS III range from 0-132. Higher scores represent a worse outcome. For some participants, a modified UPDRS III was used in which items 3.9, 3.10, 3.11, 3.12, and 3.13 were excluded to only focus on the seated portion of the assessment, or only one hemibody was tested if the aDBS controller was only controlling one subthalamic nucleus. | 30 minutes |
| Measure | Description | Time Frame |
|---|---|---|
| Disease Symptoms (Tremor) | Mean tremor power calculated from a triaxial gyroscope using a fast Fourier transform averaged between 4 and 8 Hz. Higher tremor power indicates worse tremor. | 30 minutes |
| Disease Symptoms (Freezing of Gait) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Helen Bronte-Stewart, MD MSE | Stanford University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Stanford Movement Disorders Center | Stanford | California | 94305-5235 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30833216 | Result | Velisar A, Syrkin-Nikolau J, Blumenfeld Z, Trager MH, Afzal MF, Prabhakar V, Bronte-Stewart H. Dual threshold neural closed loop deep brain stimulation in Parkinson disease patients. Brain Stimul. 2019 Jul-Aug;12(4):868-876. doi: 10.1016/j.brs.2019.02.020. Epub 2019 Feb 25. | |
| 26813875 | Result | Malekmohammadi M, Herron J, Velisar A, Blumenfeld Z, Trager MH, Chizeck HJ, Bronte-Stewart H. Kinematic Adaptive Deep Brain Stimulation for Resting Tremor in Parkinson's Disease. Mov Disord. 2016 Mar;31(3):426-8. doi: 10.1002/mds.26482. Epub 2016 Jan 27. No abstract available. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Activa PC+S Neurostimulator | Participants will be own controls and undergo both Adaptive DBS (Activa PC+S Neurostimulator) and Continuous DBS (Activa PC+S Neurostimulator) deep brain stimulation testing paradigms using Nexus D research tool PC+S: Primary Cell+Sensing |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Activa PC+S Neurostimulator | Participants will be own controls and undergo both Adaptive DBS and Continuous DBS deep brain stimulation |
| Units | Counts |
|---|---|
| Participants |
|
| 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 | Normalized Beta Band Power (13-30 Hz) During aDBS | Beta Band Power will be recorded continuously during intervention (30 minutes). The PC+S streams off power of the local field potential signal measured from the subthalamic nucleus in a frequency band of interest within the beta band (13-30 Hz). The amplitude of the signal, beta power, was streamed from each subthalamic nucleus (STN) during the calibration period of the experiment when DBS was off (i.e., OFF therapy), when continuous DBS was set at the lower and upper stimulation voltage that were found for determining the stimulation limits of adaptive DBS, and during the 30 minutes of aDBS. We calculated the median observed beta power during aDBS. To compute normalized beta band power, the median value was divided by the observed beta power OFF therapy and during the continuous DBS at the lower and upper voltage. A value less than 1 indicates reduced beta power during aDBS compared to the other conditions. | Participants who were assessed for this outcome and with no artifacts in the local field potential signal. | Posted | Mean | Standard Deviation | Normalized median beta power | 30 minutes | STNs | STNs |
|
Up to six years
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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 | Participants will be own controls and undergo both Adaptive DBS and Continuous DBS deep brain stimulation |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Infection | Infections and infestations | Systematic Assessment | serious, anticipated, device related |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Device Failure | Product Issues | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Helen Bronte-Stewart, MD, MSE | Stanford University | 650-723-6709 | bronte-stewart-lab@stanford.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP_ICF | Yes | Yes | Yes | Study Protocol, Statistical Analysis Plan, and Informed Consent Form | Jun 16, 2020 | Nov 22, 2021 | Prot_SAP_ICF_000.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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| Continuous DBS (Activa PC+S Neurostimulator) |
| Device |
|
|
Percent time freezing during a stepping-in-place task. Higher percent time freezing represents a worse outcome.
| 30 minutes |
| Disease Symptoms (Bradykinesia) | The root mean squared of the angular velocity during a wrist-flexion extension task. Higher root mean squared of angular velocity represents a better outcome. | 30 minutes |
| DBS Voltage | The median stimulation voltage during the aDBS run was determined for each individual's subthalamic nucleus. The overall group mean of the median stimulation voltages was compared to the group mean of the clinical continuous DBS (cDBS) median voltages. | 30 minutes |
| 32634599 | Result | Petrucci MN, Neuville RS, Afzal MF, Velisar A, Anidi CM, Anderson RW, Parker JE, O'Day JJ, Wilkins KB, Bronte-Stewart HM. Neural closed-loop deep brain stimulation for freezing of gait. Brain Stimul. 2020 Sep-Oct;13(5):1320-1322. doi: 10.1016/j.brs.2020.06.018. Epub 2020 Jul 4. No abstract available. |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| Mean OFF UPDRS-III at Initial Programming | Scores on the UPDRS III range from 0-132. Higher scores represent a worse outcome. | Mean | Standard Deviation | UPDRS-III Score |
|
| Title |
|---|
| Description |
|---|
| OG000 | Activa PC+S Neurostimulator | Participants will be own controls and undergo both Adaptive DBS and Continuous DBS deep brain stimulation |
|
|
|
| Primary | Change in UPDRS III Score | Movement Disorder Society's Unified Parkinson's Disease Rating Scale III (UPDRS III) score will be measured after 30 minutes of intervention and compared to baseline. Scores on the UPDRS III range from 0-132. Higher scores represent a worse outcome. For some participants, a modified UPDRS III was used in which items 3.9, 3.10, 3.11, 3.12, and 3.13 were excluded to only focus on the seated portion of the assessment, or only one hemibody was tested if the aDBS controller was only controlling one subthalamic nucleus. | Participants who were assessed for this outcome (had a clinical UPDRS assessment). | Posted | Mean | Standard Deviation | score on a scale | 30 minutes |
|
|
|
|
| Secondary | Disease Symptoms (Tremor) | Mean tremor power calculated from a triaxial gyroscope using a fast Fourier transform averaged between 4 and 8 Hz. Higher tremor power indicates worse tremor. | Participants who were assessed for this outcome and not excluded due to lack of tremor. | Posted | Mean | Standard Deviation | (rad/s)^2 | 30 minutes | STNs | STNs |
|
|
|
|
| Secondary | Disease Symptoms (Freezing of Gait) | Percent time freezing during a stepping-in-place task. Higher percent time freezing represents a worse outcome. | Participants who were assessed for this outcome and with no artifacts in the local field potential signal, artifacts in the kinematic data, or excluded since they did not identify as freezers. | Posted | Mean | Standard Deviation | percentage of time freezing | 30 minutes |
|
|
|
|
| Secondary | Disease Symptoms (Bradykinesia) | The root mean squared of the angular velocity during a wrist-flexion extension task. Higher root mean squared of angular velocity represents a better outcome. | Participants who were assessed for this outcome and with no artifacts in the local field potential signal, substantial tremor in the tested limb, or technical issues during the kinematic recording. | Posted | Mean | Standard Deviation | root mean squared of angular velocity | 30 minutes |
|
|
|
|
| Secondary | DBS Voltage | The median stimulation voltage during the aDBS run was determined for each individual's subthalamic nucleus. The overall group mean of the median stimulation voltages was compared to the group mean of the clinical continuous DBS (cDBS) median voltages. | Participants who were assessed for this outcome and with no artifacts in the local field potential signal. | Posted | Mean | Standard Deviation | median stimulation voltage | 30 minutes | STNs | STNs |
|
|
|
|
| 1 |
| 22 |
| 4 |
| 22 |
| 20 |
| 22 |
|
| Lead/Connection Break | Product Issues | Systematic Assessment | serious, anticipated, device related |
|
| Suicidality | Psychiatric disorders | Systematic Assessment | serious, unanticipated, non-device related |
|
| Femur fracture | Injury, poisoning and procedural complications | Systematic Assessment | serious, unanticipated, non-device related |
|
| Infection | Infections and infestations | Systematic Assessment |
|
| Tenderness | Surgical and medical procedures | Systematic Assessment |
|
| Sensing Malfunction | Product Issues | Systematic Assessment |
|
| Device Malfunction | Product Issues | Systematic Assessment |
|
| Gait Difficulties | Nervous system disorders | Systematic Assessment |
|
| Speech | Nervous system disorders | Systematic Assessment |
|
| Cognitive Difficulties | Nervous system disorders | Systematic Assessment |
|
| Tingling | General disorders | Systematic Assessment |
|
| Balance | General disorders | Systematic Assessment |
|
| Muscle Soreness | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Muscle Contractions | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Cognitive Problems | Nervous system disorders | Systematic Assessment |
|
| Speech Difficulties | Nervous system disorders | Systematic Assessment |
|
| Depression | Psychiatric disorders | Systematic Assessment |
|
| Suicidal Ideation | Psychiatric disorders | Systematic Assessment |
|
| Slowness | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Stiffness | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Walking Difficulty | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | Systematic Assessment |
|
| Pain/Soreness | General disorders | Systematic Assessment |
|
| Diverticulitis | Gastrointestinal disorders | Systematic Assessment |
|
| Urinary Issues | Renal and urinary disorders | Systematic Assessment |
|
| Weight changes | General disorders | Systematic Assessment |
|
| Sleep Difficulties | Nervous system disorders | Systematic Assessment |
|
| Weakness | General disorders | Systematic Assessment |
|
| Fatigue | General disorders | Systematic Assessment |
|
| Hernia | Gastrointestinal disorders | Systematic Assessment |
|
| Difficult Swallowing/Salivation | Gastrointestinal disorders | Systematic Assessment |
|
| Stroke | Nervous system disorders | Systematic Assessment |
|
| Mood | Psychiatric disorders | Systematic Assessment |
|
| Dreaming | Nervous system disorders | Systematic Assessment |
|
| Cough/Throat | Infections and infestations | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | Systematic Assessment |
|
| Dizziness | General disorders | Systematic Assessment |
|
| Restless Leg | Nervous system disorders | Systematic Assessment |
|
| Headache/Migraine | General disorders | Systematic Assessment |
|
| Delerium | Psychiatric disorders | Systematic Assessment |
|
| Vision problems | Eye disorders | Systematic Assessment |
|
| Kidney Issues | Renal and urinary disorders | Systematic Assessment |
|
| Blood Pressure | Cardiac disorders | Systematic Assessment |
|
| Body Temperature | General disorders | Systematic Assessment |
|
| Hair Loss | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
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| D009422 | Nervous System Diseases |
| D009069 | Movement Disorders |
| D000080874 | Synucleinopathies |
| D019636 | Neurodegenerative Diseases |