Adaptive Neurostimulation to Restore Sleep in Parkinson's Disease (Aim 2)

NCT05070013 | Recruiting DMC FDA Device

• 2 other identifiers: 0577-21-FB1UH3NS113769
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 2

Brief Summary

Parkinson's Disease (PD) is the second most common of the age-related neurodegenerative disorders, affecting over 1,900 adults per 100,000 over the age of 80 in the US. The prevalence of sleep dysfunction in PD is estimated at nearly 80-90% which includes sleep fragmentation, insomnia, rapid eye movement (REM or dream sleep) Sleep Behavior Disorder (RBD), Restless legs syndrome (RLS), periodic limb movement, excessive daytime sleepiness, and sleep apnea. Sleep is vital to homeostasis, cognition, and nervous system repair. The dysfunctional sleep accompanying PD adversely affects both motor and non-motor symptoms, resulting in diminished quality of life for both patients and caregivers, including impairments in mood and behavior, and increased morbidity and mortality. Knowledge of sleep phenomenology and pathology in humans has largely been informed by analysis of non-invasive scalp electroencephalogram (EEG), and despite the profound importance of sleep, the underlying neural circuits important for controlling sleep and wakefulness in humans remain poorly understood. This study assesses whether adaptive stimulation of the Subthalamic Nucleus (STN) drives changes in sleep episode maintenance and improves sleep quality. Participants are adults with PD who experience inadequate motor symptom relief, and who have been offered implantation of a deep brain stimulator system targeting STN for the treatment of motor symptoms (standard-of-care). Prior to surgery, participant sleep patterns will be assessed with questionnaires and monitored with a non-invasive watch-like device. Approximately four months after implantation surgery, participants will each receive 2 1-week deep brain stimulation (DBS) treatments and 1 1-week control session with no DBS in random order. Sleep patterns will again be monitored during the treatments and compared to the patterns before surgery.

Conditions

Parkinson's Disease; Sleep Fragmentation

Outcome Measures

Primary Outcomes (3)

• Sleep Efficiency - Frequency

  Sleep fragmentation frequency will be measured using FDA-approved wrist-based Actigraphy (ActiWatch Spectrum Pro). Comparisons will be made between baseline and each of the interventions.

  Baseline (days 1 - 21 before surgery) and intervention (approximately days 144 - 172)

• Sleep Efficiency - Duration

  Sleep fragmentation duration will be measured using FDA-approved wrist-based Actigraphy (ActiWatch Spectrum Pro). Comparisons will be made between baseline and each of the interventions.

  Baseline (days 1 - 21 before surgery) and intervention (approximately days 144 - 172)

• Subjective Sleep Quality

  Subjective sleep quality will be assessed using the Pittsburgh Sleep Diary. Comparisons will be made between baseline and each of the interventions.

  Baseline (days 1 - 21 before surgery) and intervention (approximately days 144 - 172)

Secondary Outcomes (1)

• Duration of REM Sleep Stage

  During intervention (approximately days 144 - 172)

Study Arms (3)

Adaptive Deep Brain Stimulation

EXPERIMENTAL

Participants will be given adaptive deep brain stimulation (DBS) during one week of at-home night sleep.

Device: Deep Brain Stimulation

Open-loop Deep Brain Stimulation

ACTIVE COMPARATOR

Participants will be given open-loop deep brain stimulation (DBS) (standard clinical stimulation therapy based on (DBS) programming for the treatment of motor symptoms) during one week of at-home night sleep.

Device: Deep Brain Stimulation

No Deep Brain Stimulation

NO INTERVENTION

Deep brain stimulation (DBS) is turned off (control) during one week of at-home night sleep.

Interventions

Deep Brain Stimulation DEVICE

All participants will undergo three 1-week interventions of stimulation during nighttime sleep over the course of three consecutive weeks of in-home sleep: adaptive stimulation, open-loop stimulation and no stimulation.

Adaptive Deep Brain Stimulation; Open-loop Deep Brain Stimulation

Eligibility Criteria

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

You may qualify if:

• Signed informed consent
• Diagnosis of Idiopathic Parkinson's disease (PD) with motor symptoms present for a minimum of 4 years
• Severe motor symptoms (e.g., motor fluctuations, dyskinesia, tremor, bradykinesia, rigidity) despite optimized medical therapy, that warrant surgical implantation of deep brain stimulation (DBS), according to standard clinical criteria
• Unified Parkinson's Disease Rating Scale (UPDRS-III) score off medication 20 to 80, and improvement of at least 30% in UPDRS-III score on medications, or tremor-dominant PD (score \>/= 2 on UPDRS-III tremor sub-score) or tremor in addition to other motor symptoms that are treatment-resistant and result in significant functional disability
• Appropriate trials of oral PD medications resulting in inadequate relief of motor symptoms as determined by a movement disorders neurologist, and stable dose of anti-PD medications for 30 days prior to study enrollment
• Requested and approved for subthalamic nucleus deep brain stimulation surgery (STN DBS) by study site Multi-Disciplinary Movement Disorders Patient Care Conference
• Absence of abnormalities on brain magnetic resonance imaging (MRI) scan suggestive of an alternate diagnosis or serving as a contraindication to surgery
• Absence of significant cognitive deficits or significant depression (Beck Depression Inventory-II, BDI-II, score \> 20) on formal Neuropsychological Testing
• Age 18 to 80 years (19 to 80 years in Nebraska)
• Able to conduct follow up neurological care exclusively at study site for duration of the RC+S INS neurostimulator device lifespan (9 years)

You may not qualify if:

• Any medical condition considered to elevate risk for surgical complications, such as coagulopathy,, uncontrolled hypertension, history of seizures, heart disease, inability to undergo general anesthesia, or anticoagulant medications that cannot be safely discontinued for perioperative period
• Pregnancy (women of child-bearing potential must have a negative urine pregnancy test prior to surgical procedures)
• Significant untreated depression (Beck Depression Inventory-II, BDI-II \> 20 or Geriatric Depression Scale, GDS, score \> 8)
• Personality or mood disorder symptoms that investigators believe will interfere with study requirements
• Required ongoing treatment with electroconvulsive therapy (ECT), repetitive transcranial magnetic stimulation (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 or active, drug or alcohol abuse
• Meets criteria for Parkinson's disease (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
• Restless Leg Syndrome
• Obstructive Sleep Apnea
• Inability to perform the recharge process necessary to use the RC+S brain stimulation system

Sponsors & Collaborators

• University of Nebraska: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (2)

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

RECRUITING

University of Pennsylvania Health System

Philadelphia, Pennsylvania, 19106, United States

RECRUITING

MeSH Terms

Conditions

Parkinson Disease; Sleep Deprivation

Interventions

Deep Brain Stimulation

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

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics; Surgical Procedures, Operative

Study Officials

• Aviva Abosch, MD, PhD

  University of Nebraska

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Dulce Maroni, PhD

CONTACT

402-836-9751; dmaroni@unmc.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: To mitigate bias, participants will be blinded with respect to which stimulation intervention is assigned in each week.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: All participants will experience all 3 DBS stimulation interventions (one condition per week, 3 consecutive weeks): adaptive stimulation, open-loop stimulation (standard clinical stimulation therapy) and no stimulation (control). The order of stimulation conditions is randomly assigned.

Study Record Dates

• First Submitted: September 28, 2021
• First Posted: October 6, 2021
• Study Start: November 18, 2021
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026
• Last Updated: July 22, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Starting in January 2026 after the data are published.
• Access Criteria: Researchers will be able to download the data after requesting access in DABI.

Locations

US (2)