Parkinson's Disease
Conditions
Keywords
Parkinson's Disease, DBS, Deep Brain Stimulation, Subthalamic Nucleus
Brief summary
The purpose of this study is to provide objective measurements of abnormal movements of the body in correlation with neural activity of the brain and track how these change over time. This may allow for the development of objective evaluation of the neural activity causing abnormal movements, which may lead to the ability of the DBS system to stimulate the brain by sensing the abnormal neural activity that is causing abnormal movements.
Interventions
DEVICEActiva PC+S
The Model 37604 Activa PC+S is a multiprogrammable device that can deliver therapeutic electrical stimulation and record bioelectric signals from leads implanted in the brain.
Sponsors
Medtronic
Stanford University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Resting State Beta Band Power Over Time | Baseline and 1 Year | We compared the beta band (13-30 Hz) power in the neural signal at the initial programming visit (baseline) and at the 12 month follow-up visit (1 year) after turning off deep brain stimulation therapy. Beta band power is normalized to average beta band power at the initial programming visit. Using a linear mixed model for repeated measures over time, regression beta coefficient was obtained to determine if beta power changed significantly between the initial programming and the 12 month follow-up visit. |
| Sample Beta Entropy | 1 day | Sample entropy is a measure of estimated conditional predictability, calculated within a frequency range of a patient's local field potential. Freezers are subjects who have clinical history of freezing of gait symptoms and/or if the subject displayed freezing behavior pre-operatively or during the in-study gait tasks relative to non-freezers, those who have never experienced freezing of gait. We measured sample beta (13-30 Hz) entropy in subjects' local field potential. Higher values of sample entropy indicate lower estimated conditional predictability. Testing occurred over one day, at a range of approximately 1 month to 7 months post DBS device implantation. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Activa PC+S Activa PC+S: The Model 37604 Activa PC+S is a multiprogrammable device that can deliver therapeutic electrical stimulation and record bioelectric signals from leads implanted in the brain. | 15 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 1 |
Baseline characteristics
| Characteristic | Activa PC+S |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 6 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants |
| Age, Continuous | 62.97 years STANDARD_DEVIATION 11.36 |
| 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 | 14 Participants |
| Region of Enrollment United States | 15 participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 15 |
| serious Total, serious adverse events | 0 / 15 |
Outcome results
Primary
Change in Resting State Beta Band Power Over Time
We compared the beta band (13-30 Hz) power in the neural signal at the initial programming visit (baseline) and at the 12 month follow-up visit (1 year) after turning off deep brain stimulation therapy. Beta band power is normalized to average beta band power at the initial programming visit. Using a linear mixed model for repeated measures over time, regression beta coefficient was obtained to determine if beta power changed significantly between the initial programming and the 12 month follow-up visit.
Time frame: Baseline and 1 Year
Population: 2 subjects excluded; 1 lost to follow-up, 1 had ECG artifact in neural signal
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Activa PC+S | Change in Resting State Beta Band Power Over Time | -0.28 regression beta coefficient |
p-value: 0.038Mixed Models Analysis
Primary
Sample Beta Entropy
Sample entropy is a measure of estimated conditional predictability, calculated within a frequency range of a patient's local field potential. Freezers are subjects who have clinical history of freezing of gait symptoms and/or if the subject displayed freezing behavior pre-operatively or during the in-study gait tasks relative to non-freezers, those who have never experienced freezing of gait. We measured sample beta (13-30 Hz) entropy in subjects' local field potential. Higher values of sample entropy indicate lower estimated conditional predictability. Testing occurred over one day, at a range of approximately 1 month to 7 months post DBS device implantation.
Time frame: 1 day
Population: 6 participants excluded; 3 due to tremor which may alter neural signal, 2 didn't have adequate amount of neural signal for analysis, 1 was lost to follow-up
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Activa PC+S | Sample Beta Entropy | Freezers | 0.407 Sample Entropy | Standard Deviation 0.031 |
| Activa PC+S | Sample Beta Entropy | Non-freezers | 0.337 Sample Entropy | Standard Deviation 0.062 |