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Adaptive Neurostimulation to Restore Sleep in Parkinson's Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04620551
Recruitment Status : Recruiting
First Posted : November 9, 2020
Last Update Posted : November 8, 2022
Sponsor:
Collaborators:
Stanford University
University of Colorado, Denver
University of Pennsylvania
Information provided by (Responsible Party):
Aviva Abosch, University of Nebraska

Tracking Information
First Submitted Date  ICMJE November 2, 2020
First Posted Date  ICMJE November 9, 2020
Last Update Posted Date November 8, 2022
Actual Study Start Date  ICMJE October 21, 2020
Estimated Primary Completion Date June 30, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 19, 2021)
Sleep stage duration and transitions [ Time Frame: Years 1-2 ]
We will measure pre- vs. post-stimulation impact on (1) LFP spectral composition; (2) sleep episode-specific change in duration; and (3) stimulation-induced latency to transition to next sleep episode.
Original Primary Outcome Measures  ICMJE
 (submitted: November 2, 2020)
Sleep stage detection accuracy [ Time Frame: Years 1-2 ]
We will measure the accuracy of our artificial neural network to predict sleep stage identity from the local field potentials recorded within the subthalamic nucleus. The ground truth for the sleep stage will be provided by sleep-expert evaluated polysomnography.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 19, 2021)
Sleep Quality [ Time Frame: Years 1-2 ]
Study participants will complete the Pittsburgh Sleep Diary as a measure of self-reported sleep quality and sleep disturbance.
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Adaptive Neurostimulation to Restore Sleep in Parkinson's Disease
Official Title  ICMJE Adaptive Neurostimulation to Restore Sleep in Parkinson's Disease: An Investigation of STN LFP Biomarkers in Sleep Dysregulation and Repair
Brief 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, the investigators 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, unique spectral patterns in STN oscillatory activity were identified 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, the investigators 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. Investigators 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Parkinson Disease
  • Sleep Fragmentation
Intervention  ICMJE Device: Sub-clinical stimulation
The third night of recording will involve sub-clinical thresholds of stimulation in all subjects.
Study Arms  ICMJE Experimental: PD with DBS
Patients with Parkinson's Disease who opt for DBS surgery and consent to participate in the sleep study.
Intervention: Device: Sub-clinical stimulation
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 2, 2020)
20
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 30, 2023
Estimated Primary Completion Date June 30, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Ability to provide informed consent for this study
  • Diagnosis of Idiopathic Parkinson's disease with motor symptoms that have been present for a minimum of 4 years
  • Motor symptoms are severe enough, despite optimized medical therapy, to warrant surgical implantation of DBS
  • UPDRS-III score off medication between 20 and 80, and an improvement in UPDRS-III score on medications of at least 30%, or patients with tremor-dominant PD (score >/= 2 on UPDRS-III tremor sub-score)-or tremor in addition to other motor symptoms-that is treatment-resistant and results in significant functional disability
  • Appropriate trials of oral PD medications have resulted in inadequate relief of motor symptoms
  • Absence of abnormalities on brain MRI suggestive of an alternate diagnosis or serving as a contraindication to surgery
  • Absence of significant cognitive deficits or significant depression (BDI-II score > 20) on formal Neuropsychological Testing
  • Age 21 - 80 years

Exclusion Criteria:

  • Coagulopathy, uncontrolled hypertension, history of seizures, heart disease, inability to undergo general anesthesia
  • Pregnancy
  • Significant untreated depression (BDI-II score > 20)
  • Personality or mood disorder symptoms that Study Personnel believe will interfere with study requirements
  • Patients requiring ongoing treatment with ECT, rTMS, or diathermy
  • Pre-existing implanted stimulation system (e.g., cochlear implant, cardiac pacemaker, defibrillator, neuro-stimulator for indication other than Parkinson's disease) or ferromagnetic metallic implant
  • Prior intracranial surgery
  • History of, or active, drug or alcohol abuse
  • Meets criteria for PD with Mild Cognitive Impairment (PD-MCI), as defined by Performance > 2 standard deviations below appropriate norms on tests from 2 or more of the following cognitive domains: Attention, Executive Function, Language, Memory, and Visuospatial Ability
  • Patients with Restless Leg Syndrome
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 21 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Dulce Maroni, PhD 402.836.9751 dmaroni@unmc.edu
Contact: Andrew Schnaubelt, PhD 402.559.4846 andy.schnaubelt@unmc.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04620551
Other Study ID Numbers  ICMJE 120-20-FB
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Aviva Abosch, University of Nebraska
Original Responsible Party Same as current
Current Study Sponsor  ICMJE University of Nebraska
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE
  • Stanford University
  • University of Colorado, Denver
  • University of Pennsylvania
Investigators  ICMJE
Study Director: Aviva Abosch, MD, PhD University of Nebraska
Principal Investigator: Casey Halpern, MD Stanford University
Principal Investigator: Clete Kushida, MD, PhD Stanford University
Principal Investigator: John Thompson, PhD University of Colorado, Denver
PRS Account University of Nebraska
Verification Date November 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP