Integration of Auditory, and Deep Brain Stimulation to Enhance Deep Sleep in Parkinson's Disease

NCT05184270 | Completed

• 1 other identifier: PD-LFP-AS
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

The study is an open-label trial to validate the local field potential (LFP) activity in the subthalamic nucleus (STN) for slow-wave detection during acoustic stimulation during nighttime sleep in Parkinson's disease patients that receive deep-brain-stimulation (DBS) therapy with the novel PERCEPT™ DBS system.

Conditions

Parkinson Disease

Keywords

sleep; neurodegeneration; slow-wave sleep; deep brain stimulation

Outcome Measures

Primary Outcomes (10)

• Identification of STN LFP correlates of cortical slow waves (i.e. 1-4 Hz, in the surface EEG)

  The temporal relationships of the surface EEG and the LFP will be investigated using the event-related potentials (ERP) and cross-correlation analysis.

  Through study completion, an average of 2 years

• Comparing the slope of slow wave across the night between surface EEG and STN-LFP

  In the EEG and the LFP recordings slow waves (0.5-4.5Hz) will be detected during all night NREM sleep. The slope of all detected slow-waves at the beginning of the night (i.e., first hour of sleep) will be compared to the slope of all detected slow waves at the end of the night (i.e., last hour of sleep) for the EEG and the LFP recordings separately. The overnight difference will be compared between the EEG and the LFP recordings.

  Through study completion, an average of 2 years

• Comparing the amplitude of slow wave across the night between surface EEG and STN-LFP

  In the EEG and the LFP recordings slow waves (0.5-4.5Hz) will be detected during all night NREM sleep. The amplitude of all detected slow-waves at the beginning of the night (i.e., first hour of sleep) will be compared to the slope of all detected slow waves at the end of the night (i.e., last hour of sleep) for the EEG and the LFP recordings separately. The overnight difference will be compared between the EEG and the LFP recordings.

  Through study completion, an average of 2 years

• Comparing the incidence of slow wave across the night between surface EEG and STN-LFP

  In the EEG and the LFP recordings slow waves (0.5-4.5Hz) will be detected during all night NREM sleep. The number of all detected slow-waves at the beginning of the night (i.e., first hour of sleep) will be compared to the number of all detected slow waves at the end of the night (i.e., last hour of sleep) for the EEG and the LFP recordings separately. The overnight difference will be compared between the EEG and the LFP recordings.

  Through study completion, an average of 2 years

• AS effect on SWA in the surface EEG and STN-LFP

  Comparing SWA (EEG power between 0.5-4.5Hz) during ON and OFF windows between surface EEG and STN-LFP

  Through study completion, an average of 2 years

• AS effect on the slope of slow waves in the surface EEG and STN-LFP

  Comparing the slope of slow waves of all detected slow waves during ON compared to the slope of slow waves of all detected slow waves during OFF windows between surface EEG and STN-LFP

  Through study completion, an average of 2 years

• AS effect on the amplitude of slow waves in the surface EEG and STN-LFP

  Comparing the amplitude of slow waves of all detected slow waves during ON compared to the slope of slow waves of all detected slow waves during OFF windows between surface EEG and STN-LFP

  Through study completion, an average of 2 years

• AS effect on frequencies over >4Hz

  Comparing event-related potentials (ERP) between surface EEG and STN-LFP

  Through study completion, an average of 2 years

• AS effect on frequencies over >4Hz

  Comparing time-frequency analysis of event-related spectral power (ERSP) between surface EEG and STN-LFP

  Through study completion, an average of 2 years

• AS effect on frequencies over >4Hz

  Comparing inter-trial phase coherence (ITPC) between surface EEG and STN-LFP

  Through study completion, an average of 2 years

Secondary Outcomes (5)

• Quantitative comparison of presented stimuli between recording sessions (i.e. DBS ON vs DBS OFF), i.e., total number of stimuli presented

  Through study completion, an average of 2 years

• Quantitative comparison of presented stimuli between recording sessions (i.e. DBS ON vs DBS OFF), i.e., phase targeting of AS

  Through study completion, an average of 2 years

• Quantitative comparison of presented stimuli between recording sessions (i.e. DBS ON vs DBS OFF), i.e., characterization of detected slow-waves

  Through study completion, an average of 2 years

• Quantitative comparison of presented stimuli between recording sessions (i.e. DBS ON vs DBS OFF), i.e., characterization of detected slow-waves

  Through study completion, an average of 2 years

• Investigation of relationships between behavioral performance changes and the AS effects (slow-wave characteristics in surface EEG and STN LFP) under DBS ON and OFF conditions

  Through study completion, an average of 2 years

Study Arms (1)

Sleep Measurements

EXPERIMENTAL

LFP recording from STN using externalized wires or implanted neurostimulator, while simultaneously recording clinical surface EEG and applying AS during deep sleep.

Device: Acoustic stimulation

Interventions

Acoustic stimulation DEVICE

In this project, the intervention is a presentation of low-volume non-arousing auditory stimuli during deep NREM sleep via attached headphones. Stimuli will be applied targeting the up-phase of slow waves to enhance sleep slow-wave activity. Previous studies showed that this procedure does not lead to reduced sleep quality nor result in changed sleep architecture. Therefore, no negative consequences as a result of our intervention are to be expected. In fact, it is currently applied in several other studies including children, adults, and the elderly. Importantly, stimulation is not arousing, as the sounds presented during deep sleep are brief (50 ms) and at low volume (around 50 dB). In case of arousal during sleep (detected using the surface EEG signal), the volume will be adjusted.

Sleep Measurements

Eligibility Criteria

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

You may qualify if:

• Signed informed consent
• Diagnosis of PD along with international criteria with mild to moderate disease severity (Hoehn-Yahr (HY) stages ll-lll), selected for receiving STN-DBS therapy with the neurostimulator PERCEPT™
• Sufficient German language comprehension to follow the study procedures and answer all questions related to the study outcomes
• Age above 18 years
• Negative pregnancy test during screening in female patients of childbearing potential (except in women who are surgically sterilized/hysterectomized or post-menopausal for longer than 1 year)

You may not qualify if:

• Failure to give informed consent
• Known presence of neurologic (other than PD), psychiatric, or systemic diseases (others than associated with PD)
• Clinical moderate to severe sleep-wake disorders (e.g. RLS-Index≥20, sleep apnea index ≥ 15 or, PLM-Index ≥ 15 if associated with arousals assessed during clinical PSG (in the framework of the pre-DBS work-up) and the clinical presentation of a RLS)
• Atypical or secondary Parkinsonism
• Severe medical conditions as renal insufficiency, liver failure, or congestive heart failure
• Skin disorders/problems/allergies in face/ear area that could worsen with electrode application
• Regular use of benzodiazepines other long-acting central nervous system (CNS)-depressant substances or long-acting antidepressants
• Use of melatonin less than 1 day prior to recording session
• Substance or alcohol abuse (i.e. \> 0.5 l wine or 1 l beer per day)
• High caffeine consumption (\> 5 servings/day; including coffee, energy drink)
• Known or suspected drug- or medication abuse
• Hearing deficiency resulting in inability to hear the auditory stimuli during sleep (based on results of standard pure-tone threshold audiometry)
• Not tolerating AS during screening night
• Inability to follow the procedures of the study, e.g. due to language problems or cognitive deficits
• Participation in another study with the intervention within the 30 days preceding, and during the present study

Sponsors & Collaborators

• Christian Baumann: lead
• Klinik Lengg, Zurich: collaborator
• University Children's Hospital: collaborator
• University of Zurich: collaborator

Study Sites (1)

Department of Neurology, University Hospital Zurich

Zurich, 8091, Switzerland

Location

MeSH Terms

Conditions

Parkinson Disease; Nerve Degeneration

Interventions

Acoustic Stimulation

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Therapeutics; Sensory Art Therapies; Complementary Therapies; Physical Stimulation; Investigative Techniques

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: October 15, 2021
• First Posted: January 11, 2022
• Study Start: November 10, 2021
• Primary Completion: March 7, 2023
• Study Completion: March 7, 2023
• Last Updated: September 21, 2023

Record last verified: 2023-09

Locations

CH (1)