Adaptive Neurostimulation to Restore Sleep in Parkinson's Disease: An Investigation of STN LFP Biomarkers in Sleep Dysregulation and Repair

Study First Received, November 02,2020
Lead Sponsor: University of Nebraska (Funder Type: Other)
Conditions
Parkinson Disease, Sleep Fragmentation
Study Type
Observational
Status
ongoing, recruiting (20 patients)
Study Duration
2020-10-01 to 10/2025
Overview Outcomes Eligibility Locations Investigators No Results
Overview
Official Title
Adaptive Neurostimulation to Restore Sleep in Parkinson's Disease: An Investigation of STN LFP Biomarkers in Sleep Dysregulation and Repair

Summary
Parkinson's disease (PD) is a neurodegenerative disorder that leads to both motor and non-motor symptoms. Therapies have been developed that effectively target the motor symptoms. Non-motor symptoms are far more disabling for patients, precede the onset of motor symptoms by a decade, are more insidious in onset, have been less apparent to clinicians, and are less effectively treated. Sleep dysfunction is oftentimes the most burdensome of the non-motor symptoms. There are limited options for treating sleep dysfunction in PD, and the mainstay of therapy is the use of sedative-hypnotic drugs without addressing the underlying mechanisms. Patients with PD who demonstrate significant motor fluctuations and dyskinesia are considered for subthalamic nucleus (STN) deep brain stimulation (DBS) surgery. Several studies have reported that STN-DBS also provides benefit for sleep dysregulation. Additionally, local field potentials recorded from STN DBS electrodes implanted for the treatment of PD, have led to the identification of unique patterns in STN oscillatory activity that correlate with distinct sleep cycles, offering insight into sleep dysregulation. This proposal will leverage novel investigational DBS battery technology (RC+S Summit System; Medtronic) that allows the exploration of sleep biomarkers and prototyping of closed-loop stimulation algorithms, to test the hypothesis that STN contributes to the regulation and disruption of human sleep behavior and can be manipulated for therapeutic advantage. Specifically, in PD patients undergoing STN-DBS, we will determine whether STN oscillations correlate with sleep stage transitions, then construct and evaluate sensing and adaptive stimulation paradigms that allow ongoing sleep-stage identification, and induce through adaptive stimulation an increase in duration of sleep stages associated with restorative sleep.

Detailed Description
Although STN-DBS is routinely used to treat PD motor symptoms, several studies have reported that STN-DBS also provides benefit for sleep dysregulation through normalization of sleep architecture. In our previous work, using local field potentials (LFP) recorded from STN DBS electrodes implanted for the treatment of PD, we identified unique spectral patterns in STN oscillatory activity that correlated with distinct sleep cycles, offering insight into sleep dysregulation. These findings were used to construct an Artificial Neural Network (ANN) that can accurately predict sleep stage. Building on this work with the use of new DBS battery technology that allows exploration of potential biomarkers and prototyping of closed-loop algorithms, we will test the hypothesis that STN-a highly interconnected node within the basal ganglia- contributes to the regulation and disruption of human sleep behavior and can be manipulated for therapeutic advantage. This is the first part, Aim 1, of a two-part study. We will enroll 20 subjects for Aim 1 of this study and 20 subjects for Aim 2, with 10 subjects enrolled at each clinical site for each aim (University of Nebraska Medical Center and Stanford University Medical Campus). In Aim 1, subjects will undergo standard-of-care STN DBS lead implantation surgery for the treatment of PD. They will return 3 weeks later to the in-patient Sleep Lab for 3 nights of STN LFP recordings with concurrent PSG, EMG, EOG, actigraphy, and video-EEG. The first two nights of recording will be used to establish a physiological sleep baseline for each patient. The third night of recording will involve sub-clinical thresholds of stimulation in all subjects, in an effort to favorably alter sleep-stage duration, so that NREM and REM-3 are prolonged. As a secondary outcome, subjects will be asked to complete a sleep questionnaire for all three nights, sleep during which stimulation occurred will be compared to the preceding two nights. Data collected during all three nights of recordings will be used to predict sleep stage identity from the LFPs recorded within STN, with the ground truth for each sleep stage provided by sleep-expert evaluated PSG. These data will also be used to identify the optimal sub-clinical threshold current amplitude and sleep-stage timing for adaptive stimulation to improve sleep. The stimulation algorithm developed in Aim 1 will be implemented in the second part of the study, Aim 2, to provide adaptive stimulation to subjects during nighttime sleep, over the course of 3 weeks of in-home sleep.

Arms
PD with DBS Patients with Parkinson's Disease who opt for DBS surgery and consent to participate in the sleep study.

Funder Type
Other

Lead Sponsor
University of Nebraska

Collaborators
Stanford University (Other), University of Colorado, Denver (Other)

First Received
2020-11-02

Last Updated
2020-11-02

Start Date
2020-10-01

Primary Completion
10/2025

Completion Date
10/2025

NCT Identifie
NCT04620551

Contact Information
Dulce Maroni, PhD, 402.836.9751, dmaroni@unmc.edu

Outcomes
Eligibility
Locations
Investigators
No Results