Clinical trial NCT01990313: Neural Signatures of Parkinson's Disease
Official title: Neural Signatures of Tremor, Bradykinesia and Freezing in the Subthalamic Region on Parkinson's Disease and Their Acute and Long-Term Modulation by Subthalamic Deep Brain Stimulation.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Parkinson's Disease
Keywords: Parkinson's Disease
DBS
Deep Brain Stimulation
Subthalamic Nucleus
Lead sponsor: Stanford University
Sponsor class: OTHER
Collaborators: name: Medtronic
First posted: 2013-11-21
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

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.


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

Primary outcomes:
measure: Change in Resting State Beta Band Power Over Time
timeFrame: Baseline and 1 Year
measure: Sample Beta Entropy
timeFrame: 1 day
Secondary outcomes:
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University Medical Center
state: California
Study officials:
affiliation: Stanford University
name: Helen Bronte-Stewart, MD,MSE,FAAN
role: PRINCIPAL_INVESTIGATOR
References:
citation: Quinn EJ, Blumenfeld Z, Velisar A, Koop MM, Shreve LA, Trager MH, Hill BC, Kilbane C, Henderson JM, Bronte-Stewart H. Beta oscillations in freely moving Parkinson's subjects are attenuated during deep brain stimulation. Mov Disord. 2015 Nov;30(13):1750-8. doi: 10.1002/mds.26376. Epub 2015 Sep 11.
citation: Blumenfeld Z, Koop MM, Prieto TE, Shreve LA, Velisar A, Quinn EJ, Trager MH, Bronte-Stewart H. Sixty-hertz stimulation improves bradykinesia and amplifies subthalamic low-frequency oscillations. Mov Disord. 2017 Jan;32(1):80-88. doi: 10.1002/mds.26837. Epub 2016 Nov 8.
citation: Syrkin-Nikolau J, Koop MM, Prieto T, Anidi C, Afzal MF, Velisar A, Blumenfeld Z, Martin T, Trager M, Bronte-Stewart H. Subthalamic neural entropy is a feature of freezing of gait in freely moving people with Parkinson's disease. Neurobiol Dis. 2017 Dec;108:288-297. doi: 10.1016/j.nbd.2017.09.002. Epub 2017 Sep 7.
citation: Trager MH, Koop MM, Velisar A, Blumenfeld Z, Nikolau JS, Quinn EJ, Martin T, Bronte-Stewart H. Subthalamic beta oscillations are attenuated after withdrawal of chronic high frequency neurostimulation in Parkinson's disease. Neurobiol Dis. 2016 Dec;96:22-30. doi: 10.1016/j.nbd.2016.08.003. Epub 2016 Aug 21.