Adaptive Closed Loop Neuromodulation and Neural Signatures of Parkinson's Disease (aDBS)

January 3, 2022 updated by: Helen M. Bronte-Stewart, Stanford University
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Scale (UPDRS III) and specific phenotypic measures in Parkinson's Disease compared to OFF therapy (i.e., OFF DBS and withdrawn from medication) and more efficient than cDBS.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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

22

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Stanford, California, United States, 94305-5235
        • Stanford Movement Disorders Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. A diagnosis of idiopathic Parkinson's disease, with bilateral symptoms at Hoehn and Yahr Stage greater than or equal to II.
  2. 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.
  3. 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.
  4. 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.
  5. Treatment with carbidopa/levodopa, and with a dopamine agonist at the maximal tolerated doses as determined by a movement disorders neurologist.
  6. Ability and willingness to return for study visits, at the initial programming and after three, six and twelve months of DBS.
  7. Age > 18

Exclusion Criteria:

  1. Subjects with significant cognitive impairment and/or dementia as determined by a standardized neuropsychological battery.
  2. 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.
  3. Subjects with very advanced Parkinson's disease, Hoehn and Yahr stage 5 on medication (non-ambulatory).
  4. Age > 80.
  5. Subjects with an implanted electronic device such as a neurostimulator, cardiac pacemaker/defibrillator or medication pump.
  6. Subjects, who are pregnant, are capable of becoming pregnant, or who are breast feeding.
  7. 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
  8. Subjects having a major comorbidity increasing the risk of surgery (prior stroke, severe hypertension, severe diabetes, or need for chronic anticoagulation other than aspirin).
  9. Subjects having any prior intracranial surgery.
  10. Subjects with a history of seizures.
  11. Subjects, who are immunocompromised.
  12. Subjects with an active infection.
  13. Subjects, who require diathermy, electroconvulsive therapy (ECT), or transcranial magnetic stimulation (TMS) to treat a chronic condition.
  14. Subjects, who have an inability to comply with study follow-up visits.
  15. Subjects, who are unable to understand or sign the informed consent

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: BASIC_SCIENCE
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Activa PC+S Neurostimulator

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
Device: Adaptive DBS (Activa PC+S Neurostimulator)
Other Names:
  • Adaptive deep brain stimulation
Device: Continuous DBS (Activa PC+S Neurostimulator)
Other Names:
  • continuous deep brain stimulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Normalized Beta Band Power (13-30 Hz) During aDBS
Time Frame: 30 minutes
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.
30 minutes
Change in UPDRS III Score
Time Frame: 30 minutes

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.
30 minutes

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Disease Symptoms (Tremor)
Time Frame: 30 minutes
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.
30 minutes
Disease Symptoms (Freezing of Gait)
Time Frame: 30 minutes
Percent time freezing during a stepping-in-place task. Higher percent time freezing represents a worse outcome.
30 minutes
Disease Symptoms (Bradykinesia)
Time Frame: 30 minutes
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.
30 minutes
DBS Voltage
Time Frame: 30 minutes
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.
30 minutes

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Stanford University

Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2015

Primary Completion (ACTUAL)

September 23, 2019

Study Completion (ACTUAL)

August 16, 2021

Study Registration Dates

First Submitted

February 18, 2015

First Submitted That Met QC Criteria

March 4, 2015

First Posted (ESTIMATE)

March 10, 2015

Study Record Updates

Last Update Posted (ACTUAL)

February 1, 2022

Last Update Submitted That Met QC Criteria

January 3, 2022

Last Verified

January 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 30880

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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