Neural Signatures of Parkinson's Disease

Parkinson's Disease Clinical Trial

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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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01990313
• Other study ID #: 25916
• Status: Completed
• Phase: N/A
• First received: November 6, 2013
• Last updated: January 22, 2018
• Start date: October 2013
• Est. completion date: November 2016

Study information

• Verified date: January 2018
• Source: Stanford University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: November 2016
• Est. primary completion date: November 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Parkinson Disease
• Parkinson's Disease

Intervention

Device:
• 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.

Locations

Country	Name	City	State
United States	Stanford University Medical Center	Stanford	California

Sponsors (2)

Lead Sponsor	Collaborator
Stanford University	Medtronic

Country where clinical trial is conducted

United States, 

References & Publications (4)

Blumenfeld Z, Koop MM, Prieto TE, Shreve LA, Velisar A, Quinn EJ, Trager MH, Brontë-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. Review. — View Citation

Quinn EJ, Blumenfeld Z, Velisar A, Koop MM, Shreve LA, Trager MH, Hill BC, Kilbane C, Henderson JM, Brontë-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. — View 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;10 — View 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;96:22-3 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	Baseline and 1 Year
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.	1 day