Back to resultsAdaptive Closed Loop Neuromodulation and Neural Signatures of Parkinson's Disease (aDBS)
Primary Purpose
Parkinson's Disease
Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Adaptive DBS (Activa PC+S Neurostimulator)
Continuous DBS (Activa PC+S Neurostimulator)
Sponsored by
About this trial
This is an interventional basic science trial for Parkinson's Disease
Eligibility Criteria
Inclusion Criteria:
- A diagnosis of idiopathic Parkinson's disease, with bilateral symptoms at Hoehn and Yahr Stage greater than or equal to II.
- Documented improvement in motor signs on versus off dopaminergic medication, with a change in the Unified Parkinson's Disease Rating Scale motor (UPDRS III) score of >= 30% off to on medication.
- The presence of complications of medication such as wearing off signs, fluctuating responses and/or dyskinesias, and/or medication refractory tremor, and/or impairment in the quality of life on or off medication due to these factors.
- Subjects should be on stable doses of medications, which should remain unchanged until the DBS system is activated. After the DBS system is optimized (during which time the overall medication dose may be reduced to avoid discomfort and complications such as dyskinesias) the medication dose should remain unchanged, if possible, for the duration of the study.
- Treatment with carbidopa/levodopa, and with a dopamine agonist at the maximal tolerated doses as determined by a movement disorders neurologist.
- Ability and willingness to return for study visits, at the initial programming and after three, six and twelve months of DBS.
- Age > 18
Exclusion Criteria:
- Subjects with significant cognitive impairment and/or dementia as determined by a standardized neuropsychological battery.
- Subjects with clinically active depression, defined according to the Diagnostic and Statistical manual of Mental Disorders, Fourth Edition (DSM-IV) criteria and as scored on a validated depression assessment scale.
- Subjects with very advanced Parkinson's disease, Hoehn and Yahr stage 5 on medication (non-ambulatory).
- Age > 80.
- Subjects with an implanted electronic device such as a neurostimulator, cardiac pacemaker/defibrillator or medication pump.
- Subjects, who are pregnant, are capable of becoming pregnant, or who are breast feeding.
- Patients with cortical atrophy out of proportion to age or focal brain lesions that could indicate a non-idiopathic movement disorder as determined by MRI
- Subjects having a major comorbidity increasing the risk of surgery (prior stroke, severe hypertension, severe diabetes, or need for chronic anticoagulation other than aspirin).
- Subjects having any prior intracranial surgery.
- Subjects with a history of seizures.
- Subjects, who are immunocompromised.
- Subjects with an active infection.
- Subjects, who require diathermy, electroconvulsive therapy (ECT), or transcranial magnetic stimulation (TMS) to treat a chronic condition.
- Subjects, who have an inability to comply with study follow-up visits.
- Subjects, who are unable to understand or sign the informed consent
Sites / Locations
- Stanford Movement Disorders Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Activa PC+S Neurostimulator
Arm Description
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
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
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.
Disease Symptoms (Freezing of Gait)
Percent time freezing during a stepping-in-place task. Higher percent time freezing represents a worse outcome.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02384421
Brief Title
Adaptive Closed Loop Neuromodulation and Neural Signatures of Parkinson's Disease
Acronym
aDBS
Official Title
Adaptive Closed Loop Neuromodulation and Neural Signatures of Parkinson's Disease
Study Type
Interventional
2. Study Status
Record Verification Date
January 2022
Overall Recruitment Status
Completed
Study Start Date
January 2015 (undefined)
Primary Completion Date
September 23, 2019 (Actual)
Study Completion Date
August 16, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Stanford University
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Parkinson's Disease
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
22 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Activa PC+S Neurostimulator
Arm Type
Experimental
Arm Description
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
Intervention Type
Device
Intervention Name(s)
Adaptive DBS (Activa PC+S Neurostimulator)
Other Intervention Name(s)
Adaptive deep brain stimulation
Intervention Type
Device
Intervention Name(s)
Continuous DBS (Activa PC+S Neurostimulator)
Other Intervention Name(s)
continuous deep brain stimulation
Primary Outcome Measure Information:
Title
Normalized Beta Band Power (13-30 Hz) During aDBS
Description
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.
Time Frame
30 minutes
Title
Change in UPDRS III Score
Description
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.
Time Frame
30 minutes
Secondary Outcome Measure Information:
Title
Disease Symptoms (Tremor)
Description
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.
Time Frame
30 minutes
Title
Disease Symptoms (Freezing of Gait)
Description
Percent time freezing during a stepping-in-place task. Higher percent time freezing represents a worse outcome.
Time Frame
30 minutes
Title
Disease Symptoms (Bradykinesia)
Description
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.
Time Frame
30 minutes
Title
DBS Voltage
Description
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.
Time Frame
30 minutes
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
A diagnosis of idiopathic Parkinson's disease, with bilateral symptoms at Hoehn and Yahr Stage greater than or equal to II.
Documented improvement in motor signs on versus off dopaminergic medication, with a change in the Unified Parkinson's Disease Rating Scale motor (UPDRS III) score of >= 30% off to on medication.
The presence of complications of medication such as wearing off signs, fluctuating responses and/or dyskinesias, and/or medication refractory tremor, and/or impairment in the quality of life on or off medication due to these factors.
Subjects should be on stable doses of medications, which should remain unchanged until the DBS system is activated. After the DBS system is optimized (during which time the overall medication dose may be reduced to avoid discomfort and complications such as dyskinesias) the medication dose should remain unchanged, if possible, for the duration of the study.
Treatment with carbidopa/levodopa, and with a dopamine agonist at the maximal tolerated doses as determined by a movement disorders neurologist.
Ability and willingness to return for study visits, at the initial programming and after three, six and twelve months of DBS.
Age > 18
Exclusion Criteria:
Subjects with significant cognitive impairment and/or dementia as determined by a standardized neuropsychological battery.
Subjects with clinically active depression, defined according to the Diagnostic and Statistical manual of Mental Disorders, Fourth Edition (DSM-IV) criteria and as scored on a validated depression assessment scale.
Subjects with very advanced Parkinson's disease, Hoehn and Yahr stage 5 on medication (non-ambulatory).
Age > 80.
Subjects with an implanted electronic device such as a neurostimulator, cardiac pacemaker/defibrillator or medication pump.
Subjects, who are pregnant, are capable of becoming pregnant, or who are breast feeding.
Patients with cortical atrophy out of proportion to age or focal brain lesions that could indicate a non-idiopathic movement disorder as determined by MRI
Subjects having a major comorbidity increasing the risk of surgery (prior stroke, severe hypertension, severe diabetes, or need for chronic anticoagulation other than aspirin).
Subjects having any prior intracranial surgery.
Subjects with a history of seizures.
Subjects, who are immunocompromised.
Subjects with an active infection.
Subjects, who require diathermy, electroconvulsive therapy (ECT), or transcranial magnetic stimulation (TMS) to treat a chronic condition.
Subjects, who have an inability to comply with study follow-up visits.
Subjects, who are unable to understand or sign the informed consent
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Helen Bronte-Stewart, MD MSE
Organizational Affiliation
Stanford University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Stanford Movement Disorders Center
City
Stanford
State/Province
California
ZIP/Postal Code
94305-5235
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
30833216
Citation
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.
Results Reference
result
PubMed Identifier
26813875
Citation
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.
Results Reference
result
PubMed Identifier
32634599
Citation
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.
Results Reference
result
Learn more about this trial
Adaptive Closed Loop Neuromodulation and Neural Signatures of Parkinson's Disease
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