Adaptive Neurostimulation to Restore Sleep in Parkinson's Disease

NCT04620551 | Active Not Recruiting DMC FDA Device

• 1 other identifier: 0120-20-FB
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Parkinson Disease; Sleep Fragmentation

Outcome Measures

Primary Outcomes (1)

• Sleep stage duration and transitions

  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.

  Years 1-2

Secondary Outcomes (1)

• Sleep Quality

  Years 1-2

Study Arms (1)

PD with DBS

EXPERIMENTAL

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

Device: Sub-clinical stimulation

Interventions

Sub-clinical stimulation DEVICE

The third night of recording will involve sub-clinical thresholds of stimulation in all subjects.

PD with DBS

Eligibility Criteria

• Age: 21 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Nebraska: lead
• Stanford University: collaborator
• University of Pennsylvania: collaborator
• University of Colorado, Denver: collaborator

Study Sites (1)

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Related Publications (2)

• Das R, Gliske SV, West LC, Summers MO, Tang S, Hirt L, Maroni D, Halpern CH, Thompson JA, Kushida CA, Abosch A. Sleep macro-architecture in patients with Parkinson's disease does not change during the first night of neurostimulation in a pilot study. J Clin Sleep Med. 2024 Sep 1;20(9):1489-1496. doi: 10.5664/jcsm.11180.

  PMID: 38652493 DERIVED

• West LC, Summers M, Tang S, Hirt L, Halpern CH, Maroni D, Das R, Gliske SV, Abosch A, Kushida CA, Thompson JA. Evaluation of consensus sleep stage scoring of dysregulated sleep in Parkinson's disease. Sleep Med. 2023 Jul;107:236-242. doi: 10.1016/j.sleep.2023.04.031. Epub 2023 May 18.

  PMID: 37257366 DERIVED

MeSH Terms

Conditions

Parkinson Disease; Sleep Deprivation

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Dyssomnias; Sleep Wake Disorders; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Mental Disorders

Study Officials

• Aviva Abosch, MD, PhD

  University of Nebraska

  STUDY DIRECTOR

• Casey Halpern, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

• Clete Kushida, MD, PhD

  Stanford University

  PRINCIPAL INVESTIGATOR

• John Thompson, PhD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 2020
• First Posted: November 9, 2020
• Study Start: October 21, 2020
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: August 19, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)