NCT03582891

The Motor Network in Parkinson's Disease and Dystonia: Mechanisms of Therapy

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

• Status: Active Not Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 25 (estimated)
• Sponsor: University of California, San Francisco · Academic / Other
• Sex: All
• Age: 21 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

This is an exploratory pilot study to identify neural correlates of specific motor signs in Parkinson's disease (PD) and dystonia, using a novel totally implanted neural interface that senses brain activity as well as delivering therapeutic stimulation. Parkinson's disease and isolated dystonia patients will be implanted unilaterally or bilaterally with a totally internalized bidirectional neural interface, Medtronic Summit RC+S. This study includes three populations: ten PD patients undergoing deep brain stimulation in the subthalamic nucleus (STN), ten PD patients with a globus pallidus (GPi) target and five dystonia patients. All groups will test a variety of strategies for feedback-controlled deep brain stimulation, and all patients will undergo a blinded, small pilot clinical trial of closed-loop stimulation for thirty days.

Detailed description

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. Investigators will also study neural signals of sleep and test stimulation to support specific sleep stages. 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.

Conditions

• Parkinson Disease
• Dystonia

Interventions

Type	Name	Description
DEVICE	Summit RC+S for Motor	Using the RC+S pulse generator, investigators will measure cortical biomarkers of hyper and hypokinesia in Parkinson's and dystonia patients to develop an adaptive algorithm which adjusts the level of deep brain stimulation needed based upon the patient's physiology.
DIAGNOSTIC_TEST	8-week pilot trial of Closed-loop vs. Open-loop Stimulation	These patients will participate in an 8 week clinical trial of open loop versus adaptive mode (4 weeks for each mode (interleaved), with the order counterbalanced across subjects ).
DEVICE	Summit RC+S for Sleep	Using the RC+S pulse generator, investigators will measure cortical biomarkers of sleep stages in Parkinson's patients to develop an adaptive algorithm which adjusts the level of deep brain stimulation needed based upon the patient's physiology.

Timeline

• Start date: 2018-10-01
• Primary completion: 2025-12-31
• Completion: 2028-03-01
• First posted: 2018-07-11
• Last updated: 2025-04-13

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated device study