Summary

for people ages 25-75 (full criteria)
study started
estimated completion:
Philip Starr

Description

Summary

This is an exploratory pilot study to test a variety of strategies for feedback-controlled deep brain stimulation. Twenty Parkinson's disease patients with motor fluctuations and will be implanted bilaterally with a totally internalized bidirectional neural interface, Medtronic Activa RC+S. Each RC+S will be attached to both quadripolar subthalamic DBS lead, and quadripolar subdural cortical paddle lead. Investigators will collect and characterize each subject's physiological biomarkers related to the hypokinetic and hyperkinetic state to prototype classifier/control algorithms both in vitro and during a brief in-clinic test in study subjects. There will be a small pilot clinical trial in which individualized classifier/control strategies for each hemisphere in each subject will be embedded within the RC+S for one month of feedback-controlled stimulation, to be compared with one month of empirically optimized open-loop stimulation, administered in randomized order with closed-loop stimulation.

Official Title

Closed Loop Deep Brain Stimulation in Parkinson's Disease (Activa RC+S)

Details

In this project investigators will develop adaptive DBS algorithms based on cortical and subcortical signals using the RC+S. This bidirectional neural interface is rechargeable (for up to 9 years of use), and is capable of delivering therapeutic open-loop stimulation or closed-loop stimulation. Its sensing capability includes four simultaneous time series channels at up to 1000 Hz sampling rate. In addition the device can stream time series data, and calculate and stream spectral power within a preset bandwidth. Twenty patients with idiopathic PD and motor fluctuations, or medically intractable tremor, will be implanted with unilateral or bilateral RC+S devices, each connected to a standard quadripolar DBS lead implanted in STN or globus pallidus, and to a 4-contact paddle type electrode placed subdurally over sensorimotor cortex. The basal ganglia lead will be used for both stimulation and LFP recordings, while the cortical lead will be used only for recording ECoG potentials, not for stimulation.

Patients with motor fluctuations cycle between a hypokinetic state (too little movement) and a hyperkinetic state (excessive movement). During open-loop DBS, brain state continues to fluctuate between these states and stimulation may induce dyskinesia or inadequately relieve akinesia. With the goal of maintaining motor function within a normal range away from these two extremes, investigators will develop and test stimulation algorithms that utilize putative markers of both kinetic states. The basic strategy is to automatically adjust stimulation parameters until the physiological signature of abnormal function is minimized. First, investigators will prototype adaptive stimulation paradigms and briefly (2 hours) test them in clinic, using a "distributed" configuration (streaming to a computer). Then, investigators will embed these algorithms in RC+S to test chronic and fully closed-loop DBS in a small double-blinded clinical trial. Investigators will pay careful attention to the possibility of progressive reduction in stimulation currents over the course of the study, which could support the hypothesis that "adaptive stimulation" might make the brain progressively less dependent on the device.

In quantifying DBS amplitude and comparing open loop with adaptive stimulation, an important parameter is the total electrical energy delivered (TEED). TEED is calculated by the following equation as suggested by Koss and colleagues (TEED1sec = ((voltage2 x frequency x pulsewidth)/impedance) x 1sec). This can be used as measure of the energy saved when stimulation is delivered in closed-loop mode relative to empiric open-loop stimulation.

Keywords

Parkinson Disease Dystonia Summit RC+S Closed-loop trial at 11 months Closed-loop trial at 12 months

Eligibility

You can join if…

Open to people ages 25-75

  1. Ability to give informed consent for the study
  2. Movement disorder symptoms that are sufficiently severe, in spite of best medical therapy, to warrant surgical implantation of deep brain stimulators according to standard clinical criteria
  3. Patient has requested surgical intervention with deep brain stimulation for their disorder
  4. No MR abnormalities that suggest an alternative diagnosis or contraindicate surgery
  5. Absence of significant cognitive impairment (score of 20 or greater on the Montreal Cognitive Assessment (MoCA),
  6. Signed informed consent
  7. Ability to comply with study follow-up visits for brain recording, testing of adaptive stimulation, and clinical assessment.
  8. Age 25-75
  9. Diagnosis of idiopathic PD with duration of motor symptoms for 4 years or greater
  10. . Patient has undergone appropriate therapy with oral medications with inadequate relief as determined by a movement disorders neurologist, and has had stable doses of antiparkinsonian medications for 30 days prior to baseline assessment.
  11. . UPDRS-III score off medication between 20 and 80 and an improvement of at least 30% in the baseline UPDRS-III on medication score, compared to the baseline off-medication score, and motor fluctuations with at least 2 hours per day of on time without dyskinesia or with non-bothersome dyskinesia.

OR Patients with tremor-dominant PD (a tremor score of at least 2 on a UPDRS-III sub-score for tremor), treatment resistant, with significant functional disability despite maximal medical management

You CAN'T join if...

  1. Coagulopathy, anticoagulant medications, uncontrolled hypertension, history of seizures, heart disease, or other medical conditions considered to place the patient at elevated risk for surgical complications
  2. Evidence of a psychogenic movement disorder: Motor symptoms that remit with suggestion or "while unobserved", symptoms that are inconsistent over time or incongruent with clinical condition, plus other manifestation such as "false" signs, multiple somatizations, or obvious psychiatric disturbance.
  3. Pregnancy: all women of child bearing potential will have a negative urine pregnancy test prior to undergoing their surgical procedure.
  4. Significant untreated depression (BDI-II score >20) History of suicidal attempt or active suicidal ideation (Yes to #2-5 on C-SSRS)
  5. Any personality or mood symptoms that study personnel believe will interfere with study requirements.
  6. Subjects who require ECT, rTMS or diathermy
  7. Implanted stimulation systems such as; cochlear implant, pacemaker, defibrillator,neurostimulator or metallic implant
  8. Previous cranial surgery
  9. Drug or alcohol abuse
  10. . Meets criteria for Parkinson's disease with mild cognitive impairment (PD-MCI). These criteria are: performance of more than two standard deviations below appropriate norms, for tests from two or more of these five cognitive domains: attention,executive function, language, memory, and visuospatial tests.

Lead Scientist

  • Philip Starr
    Dr. Starr is Professor of Neurological Surgery and holds the Dolores Cakebread Endowed Chair in Neurological Surgery. His clinical interests are in functional neurosurgery, especially in the use of implanted devices to improve brain function.

Details

Status
not yet accepting patients
Start Date
Completion Date
(estimated)
Sponsor
University of California, San Francisco
ID
NCT03582891
Study Type
Interventional
Last Updated