BrainRadio: Neural Signatures of Parkinson's Disease

• Sponsor: Stanford University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01990313
• Collaborator: Medtronic (Industry)
• Enrollment: 15
• Location: 1
• Arm: 1
• Duration (Months): 37
• Patients Per Site Per Month: 0.4

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Parkinson's Disease	Device: Activa PC+S	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 15 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• 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 Start Date: Oct 1, 2013
• Actual Primary Completion Date: Nov 1, 2016
• Actual Study Completion Date: Nov 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Activa PC+S	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.; Other Names: Model 37604

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford University Medical Center	Stanford	California	United States	94305

Sponsors and Collaborators

• Stanford University
• Medtronic

Investigators

• Principal Investigator: Helen Bronte-Stewart, MD,MSE,FAAN, Stanford University

Study Documents (Full-Text)

None provided.

More Information

Publications

• 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.
• 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.

• Responsible Party: Helen M. Bronte-Stewart, Dr, Stanford University
• ClinicalTrials.gov Identifier: NCT01990313
• Other Study ID Numbers: 25916
• First Posted: Nov 21, 2013
• Last Update Posted: Feb 20, 2018
• Last Verified: Jan 1, 2018

• Keywords provided by Helen M. Bronte-Stewart, Dr, Stanford University: Parkinson's Disease; DBS; Deep Brain Stimulation; Subthalamic Nucleus
• Additional relevant MeSH terms: Parkinson Disease

Study Results

Participant Flow

Arm/Group Title	Activa PC+S
Arm/Group Description	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.
Period Title: Overall Study
STARTED	15
COMPLETED	14
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Activa PC+S
Arm/Group Description	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.
Overall Participants	15
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	9 60%
>=65 years	6 40%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	62.97 (11.36)
Sex: Female, Male (Count of Participants)
Female	3 20%
Male	12 80%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 6.7%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	14 93.3%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	15 100%

Outcome Measures

1. Primary Outcome

Title	Change in Resting State Beta Band Power Over Time
Description	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

Outcome Measure Data

Analysis Population Description

2 subjects excluded; 1 lost to follow-up, 1 had ECG artifact in neural signal

Arm/Group Title	Activa PC+S
Arm/Group Description	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.
Measure Participants	13
Number [regression beta coefficient]	-0.28

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Activa PC+S
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.038
	Comments
	Method	Mixed Models Analysis
	Comments

2. Primary Outcome

Title	Sample Beta Entropy
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Activa PC+S
Arm/Group Description	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.
Measure Participants	9
Freezers	0.407 (0.031)
Non-freezers	0.337 (0.062)

Adverse Events

Time Frame	2 years
Arm/Group Title	Activa PC+S
Arm/Group Description	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.
All Cause Mortality
	Activa PC+S
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Activa PC+S
	Affected / at Risk (%)	# Events
Total	0/15 (0%)
Other (Not Including Serious) Adverse Events
	Activa PC+S
	Affected / at Risk (%)	# Events
Total	0/15 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.