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Auditory Slow Wave Enhancement in Parkinson Disease and Mild Cognitive Impairment (PDMCI-TS)

Primary Purpose

Parkinson Disease, Mild Cognitive Impairment

Status
Recruiting
Phase
Not Applicable
Locations
Switzerland
Study Type
Interventional
Intervention
TSB Axo
Sponsored by
University of Zurich
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Parkinson Disease focused on measuring Parkinson Disease, Mild Cognitive Impairment, Excessive Daytime Sleepiness, Sleep, Slow wave sleep, Auditory enhancement, Neurodegeneration, Cognition

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • PD: Diagnosis of PD along international criteria, with mild to moderate disease severity (Hoehn and Yahr scale, stages ll-lll)
  • PD: Ability to apply the intervention for the duration of study
  • MCI: Diagnosis of MCI along international criteria, with a predominant amnestic presentation (single- or multi-domain amnestic MCI)
  • MCI: Presence of a cohabitant person who could assist with the application
  • MCI: Ability to apply the intervention for the duration of study, with assistance of co-habitant if needed

PD and MCI:

  • Age above 18 years
  • Informed consent as documented by signature
  • Stable home situation (e.g. long-term place to live) that allows for reliable application of intervention for the duration of the study
  • Sufficient German language comprehension to follow the study procedures and answer all questions related to the study outcomes
  • Dosing of dopaminergic, cholinergic, and other PD or MCI medication must have been stable for at least 14 days prior to start of the first intervention
  • Negative pregnancy test during screening (except in women who are surgically sterilized/hysterectomized or postmenopausal for longer than 1 year)

Exclusion Criteria:

  • PD: Presence of neurologic, psychiatric, or sleep disorders (others than associated with PD)
  • PD: Parkinsonism without response to levodopa; Atypical Parkinsonian syndromes
  • PD: Cognitive impairment (Montréal Cognitive Assessment [MoCA] <24)
  • MCI: Present diagnosis of a neurological (other than MCI) or interfering psychiatric disease or sleep disorder (e.g. sleep apnoea syndrome, restless legs syndrome)

PD and MCI:

  • Severe medical conditions as renal insufficiency, liver failure or congestive heart failure
  • Regular use of the following drugs: Benzodiazepines and other central nervous system (CNS)-depressant substances, melatonin and other sleep inducing substances, approved drugs for Alzheimer-type dementia (acetylcholine-esterase inhibitor, memantine)
  • Inability to hear the tones produced by the TSB Axo
  • Skin disorders/problems/allergies in face/ear area that could worsen with electrode application
  • Known or suspected drug- or medication abuse
  • Known or suspected non-compliance
  • Participation in another study with investigational drug or investigational medical devices within the 30 days preceding and during the present study
  • Previous enrolment in the current study
  • Enrolment of the investigator, his/her family members, employees and other dependent persons
  • Shift work (work during the night)
  • Travelling more than 2 time zones in the last month before intervention starts or during intervention (start of intervention will be adapted to fit with this criteria)
  • 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)
  • Implanted deep brain stimulation electrodes
  • Women who are pregnant or breast feeding
  • Intention to become pregnant during the course of the study
  • Lack of safe contraception, defined as: Female patients of childbearing potential, not using and not willing to continue using a medically reliable method of contraception for the entire study duration, such as oral, injectable, or implantable contraceptives, or intrauterine contraceptive devices, or who are not using any other method considered sufficiently reliable by the investigator in individual cases

Sites / Locations

  • University Hospital Zurich, Neurology departmentRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Sham Comparator

Arm Label

Verum

Sham

Arm Description

The device records EEG and other biosignals throughout the night and scans these signals for slow waves associated with deep Non-Rapid Eye Movement (NREM) sleep. Upon recognition of such slow waves and fulfilment of other criteria, a tone is played via the headphones to stimulate and enhance slow waves without waking up the patient.

Playing no tones during NREM sleep but wearing the device and recording the biosignals over a period of 2 weeks, every night.

Outcomes

Primary Outcome Measures

Difference in objective EDS
Difference in objective excessive daytime sleepiness (EDS), measured with Multiple Sleep Latency Test (MSLT; minutes), in Parkinson patients
Difference in verbal episodic memory performance
Difference in verbal episodic memory performance, measured with the Hopkins Verbal Learning Test (HVLT; score ranges from 0 to 12, higher scores indicate better performance) delayed recall, in Mild Cognitive Impairment patients

Secondary Outcome Measures

Subjective EDS
Change in subjective excessive daytime sleepiness (EDS), measured with the Epworth Sleepiness Scale (ESS; score ranges from 0 to 24, higher scores indicate greater EDS)
Sustained attention
Sustained attention, measured with the Sustained Attention to Response Task (SART)
Vigilance
Vigilance, measured with the Psychomotor Vigilance Task (PVT)
Subjective nocturnal sleep quality
Subjective nocturnal sleep quality, measured with the Parkinson's Disease Sleep Scale -2 (PDSS-2; score ranges from 0 to 60, higher scores indicate worse sleep quality) in PD patients and Pittsburgh Sleep Quality Index (PSQI; score ranges from 0 to 21, higher scores indicate worse sleep quality) in MCI patients
Executive Function and attention
Executive function (mental flexibility, verbal fluency, motor programming, sensitivity to interference, working memory, psychomotor processing speed), measured with the Trail Making Test (TMT; in seconds) B/A, the Regensburger Wortflüssigkeitstest (RWT; phonematic and semantic verbal fluency; in word count), the Luria's motor sequence test, the Victoria Stroop Task, the 2-back task, and the TMT A
Plasma biomarkers
Plasma levels of protein accumulation (aSyn, beta-amyloid 40 and 42 [Aß40, Aß40], tau, phosphorylated tau [p-tau]), neurodegeneration (neurofilament light chain; NFL), and synaptic and inflammatory markers
Subjective sleep quality
Subjective sleep quality measured with a Visual Analog Scale (VAS) on a scale from very poor to very good
Subjective mood
Subjective mood during daytime measured with a Visual Analog Scale (VAS) on a scale from very poor to very good
Subjective momentary sleepiness
Subjective momentary sleepiness measured with Karolinska Sleepiness Scale (KSS; score ranges from 1 to 9, higher scores indicate greater momentary sleepiness)
Digital biomarkers
tapping behavior on tablet
Sleep intensity
Sleep intensity, represented by Slow Wave Activity/ Slow Wave Energy (SWA/SWE), calculated from EEG recordings obtained every night at home with a frontal EEG electrode of the TSB Axo
Depressive symptoms
Depressive symptoms, indicated by the Hospital Anxiety and Depression Scale (HADS; score ranges from 0 to 21, higher scores indicate more depressive symptoms), in MCI patients
Verbal episodic and visuospatial memory function
Verbal episodic and visuospatial memory function, measured with the Hopkins Verbal Learning Test (HVLT; score ranges from 0 to 12, higher scores indicate better performance), and Brief Visuospatial Memory Test (BVMT; score ranges from 0 to 12, higher scores indicate better performance), in MCI patients
Quality of life (VAS)
Quality of life, measured with a Visual Analog Scale (VAS) on a scale from very poor to very good, in Parkinson patients
Motor symptoms
Motor symptoms, assessed with the Unified Parkinson's Disease Rating Scale (UPDRS) lll remote version (on tablet; score ranges from 0 to 104, higher scores indicate worse motor symptoms), in Parkinson patients
Focused motor assessment
Assessment of hand/finger movements, in Parkinson patients
Overnight memory consolidation
Overnight memory consolidation, assessed with a word-pair task and finger tapping sequence test in PD and MCI patients
Overnight restoration inhibitory control
Overnight restoration of inhibitory control, assessed with the Go/NoGo Task (GNG) in PD and MCI patients
Overnight restoration working memory
Overnight restoration of the working memory, assessed by the 2-back task in PD and MCI patients
Overnight restoration vigilance
Overnight restoration of vigilance, assessed by the Psychomotor Vigilance Test (PVT) in PD and MCI patients

Full Information

First Posted
January 25, 2021
Last Updated
November 14, 2022
Sponsor
University of Zurich
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1. Study Identification

Unique Protocol Identification Number
NCT04736017
Brief Title
Auditory Slow Wave Enhancement in Parkinson Disease and Mild Cognitive Impairment
Acronym
PDMCI-TS
Official Title
Assessing Effects of Auditory Slow Wave Enhancement on Symptoms and Biomarker Levels in Parkinson Disease and Mild Cognitive Impairment: A Randomized, Double-Blind and Placebo- Controlled Crossover Study
Study Type
Interventional

2. Study Status

Record Verification Date
November 2022
Overall Recruitment Status
Recruiting
Study Start Date
April 1, 2021 (Actual)
Primary Completion Date
March 31, 2024 (Anticipated)
Study Completion Date
March 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Zurich

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The study aims to assess the efficacy of auditory slow-wave sleep (SWS) enhancement in PD patients and patients with amnestic MCI. Patients will be randomized to two groups: Group 1 will first be treated with auditory stimulation for two weeks and then - after a washout period - switched to two weeks of sham stimulation. Group 2 will first receive sham stimulation for two weeks and then - after a washout period - switch to two weeks of auditory stimulation treatment. The washout period in between will be 2-4 weeks.
Detailed Description
The study is a randomized, double-blind, sham-controlled cross-over trial to assess the efficacy of auditory slow-wave sleep (SWS) enhancement in PD patients and patients with amnestic MCI. The screening phase includes entry questionnaires about inclusion/exclusion criteria, sleep quality, chronotype, and handedness, and 1-4 screening nights at home with the TSB Axo, to allow for stimulation optimization. One of the screening nights will be extended to screen for sleep apnea and periodic limb movements during sleep using an ambulatory screening device. Upon final inclusion, 24 PD and 24 MCI patients will be enrolled in the study for an overall period of 6-8 weeks (not including screening phase). Patients will receive 2 weeks of auditory SWS enhancement and 2 weeks of sham stimulation (only device application, no tones played) in a counter-balanced cross-over design, with a 2-4 week washout period during cross-over. Study visits will be performed immediately before and after each intervention period, i.e. after 2 weeks of auditory stimulation or sham stimulation, respectively. Study visits will include standardized clinical examinations, symptom questionnaires, blood sampling after intervention and screening for adverse events by a study physician. Study visits will take place at the Department of Neurology, University Hospital Zurich.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Parkinson Disease, Mild Cognitive Impairment
Keywords
Parkinson Disease, Mild Cognitive Impairment, Excessive Daytime Sleepiness, Sleep, Slow wave sleep, Auditory enhancement, Neurodegeneration, Cognition

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Model Description
The study is a randomized, double-blind, sham-controlled cross-over trial.
Masking
ParticipantCare ProviderOutcomes Assessor
Allocation
Randomized
Enrollment
48 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Verum
Arm Type
Experimental
Arm Description
The device records EEG and other biosignals throughout the night and scans these signals for slow waves associated with deep Non-Rapid Eye Movement (NREM) sleep. Upon recognition of such slow waves and fulfilment of other criteria, a tone is played via the headphones to stimulate and enhance slow waves without waking up the patient.
Arm Title
Sham
Arm Type
Sham Comparator
Arm Description
Playing no tones during NREM sleep but wearing the device and recording the biosignals over a period of 2 weeks, every night.
Intervention Type
Device
Intervention Name(s)
TSB Axo
Intervention Description
The TSB Axo is a wearable biosignal recording device combined with an auditory stimulation. The device consists of pre-gelled biosignal electrodes, headphones integrated in a headband, and a biosignal processing module.
Primary Outcome Measure Information:
Title
Difference in objective EDS
Description
Difference in objective excessive daytime sleepiness (EDS), measured with Multiple Sleep Latency Test (MSLT; minutes), in Parkinson patients
Time Frame
assessed after each intervention (day 15 of each intervention)
Title
Difference in verbal episodic memory performance
Description
Difference in verbal episodic memory performance, measured with the Hopkins Verbal Learning Test (HVLT; score ranges from 0 to 12, higher scores indicate better performance) delayed recall, in Mild Cognitive Impairment patients
Time Frame
assessed after each intervention (day 15 of each intervention)
Secondary Outcome Measure Information:
Title
Subjective EDS
Description
Change in subjective excessive daytime sleepiness (EDS), measured with the Epworth Sleepiness Scale (ESS; score ranges from 0 to 24, higher scores indicate greater EDS)
Time Frame
assessed before and after each intervention (day 1 and 15 of each intervention)
Title
Sustained attention
Description
Sustained attention, measured with the Sustained Attention to Response Task (SART)
Time Frame
assessed after each intervention (day 15 of each intervention)
Title
Vigilance
Description
Vigilance, measured with the Psychomotor Vigilance Task (PVT)
Time Frame
assessed after each intervention (day 15 of each intervention)
Title
Subjective nocturnal sleep quality
Description
Subjective nocturnal sleep quality, measured with the Parkinson's Disease Sleep Scale -2 (PDSS-2; score ranges from 0 to 60, higher scores indicate worse sleep quality) in PD patients and Pittsburgh Sleep Quality Index (PSQI; score ranges from 0 to 21, higher scores indicate worse sleep quality) in MCI patients
Time Frame
assessed before and after each intervention (day 1 and 15 of each intervention)
Title
Executive Function and attention
Description
Executive function (mental flexibility, verbal fluency, motor programming, sensitivity to interference, working memory, psychomotor processing speed), measured with the Trail Making Test (TMT; in seconds) B/A, the Regensburger Wortflüssigkeitstest (RWT; phonematic and semantic verbal fluency; in word count), the Luria's motor sequence test, the Victoria Stroop Task, the 2-back task, and the TMT A
Time Frame
assessed after each intervention (day 15 of each intervention)
Title
Plasma biomarkers
Description
Plasma levels of protein accumulation (aSyn, beta-amyloid 40 and 42 [Aß40, Aß40], tau, phosphorylated tau [p-tau]), neurodegeneration (neurofilament light chain; NFL), and synaptic and inflammatory markers
Time Frame
assessed after each intervention (day 15 of each intervention)
Title
Subjective sleep quality
Description
Subjective sleep quality measured with a Visual Analog Scale (VAS) on a scale from very poor to very good
Time Frame
assessed every morning during the intervention period (days 1-15 of each intervention)
Title
Subjective mood
Description
Subjective mood during daytime measured with a Visual Analog Scale (VAS) on a scale from very poor to very good
Time Frame
assessed every evening during the intervention period (days 1-14 of each intervention)
Title
Subjective momentary sleepiness
Description
Subjective momentary sleepiness measured with Karolinska Sleepiness Scale (KSS; score ranges from 1 to 9, higher scores indicate greater momentary sleepiness)
Time Frame
assessed every evening during the intervention period (days 1-14 of each intervention)
Title
Digital biomarkers
Description
tapping behavior on tablet
Time Frame
assessed every day during the intervention (days 1-15 of each intervention)
Title
Sleep intensity
Description
Sleep intensity, represented by Slow Wave Activity/ Slow Wave Energy (SWA/SWE), calculated from EEG recordings obtained every night at home with a frontal EEG electrode of the TSB Axo
Time Frame
assessed continuously during the intervention period (days 1-15 of each intervention)
Title
Depressive symptoms
Description
Depressive symptoms, indicated by the Hospital Anxiety and Depression Scale (HADS; score ranges from 0 to 21, higher scores indicate more depressive symptoms), in MCI patients
Time Frame
assessed before and after each intervention (day 1 and 15 of each intervention)
Title
Verbal episodic and visuospatial memory function
Description
Verbal episodic and visuospatial memory function, measured with the Hopkins Verbal Learning Test (HVLT; score ranges from 0 to 12, higher scores indicate better performance), and Brief Visuospatial Memory Test (BVMT; score ranges from 0 to 12, higher scores indicate better performance), in MCI patients
Time Frame
assessed after each intervention (day 15 of each intervention)
Title
Quality of life (VAS)
Description
Quality of life, measured with a Visual Analog Scale (VAS) on a scale from very poor to very good, in Parkinson patients
Time Frame
assessed before and after each intervention (day 1 and 14, day 29 and 42)
Title
Motor symptoms
Description
Motor symptoms, assessed with the Unified Parkinson's Disease Rating Scale (UPDRS) lll remote version (on tablet; score ranges from 0 to 104, higher scores indicate worse motor symptoms), in Parkinson patients
Time Frame
assessed before and after each intervention, in the morning prior to dopaminergic medication intake (day 1 and 14 of each intervention)
Title
Focused motor assessment
Description
Assessment of hand/finger movements, in Parkinson patients
Time Frame
assessed on day 4 of each intervention
Title
Overnight memory consolidation
Description
Overnight memory consolidation, assessed with a word-pair task and finger tapping sequence test in PD and MCI patients
Time Frame
assessed in the evening of day 13 and in the morning of day 14
Title
Overnight restoration inhibitory control
Description
Overnight restoration of inhibitory control, assessed with the Go/NoGo Task (GNG) in PD and MCI patients
Time Frame
assessed in the evening of day 13 and in the morning of day 14
Title
Overnight restoration working memory
Description
Overnight restoration of the working memory, assessed by the 2-back task in PD and MCI patients
Time Frame
assessed in the evening of day 13 and in the morning of day 14
Title
Overnight restoration vigilance
Description
Overnight restoration of vigilance, assessed by the Psychomotor Vigilance Test (PVT) in PD and MCI patients
Time Frame
assessed in the evening of day 13 and in the morning of day 14

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: PD: Diagnosis of PD along international criteria, with mild to moderate disease severity (Hoehn and Yahr scale, stages ll-lll) PD: Ability to apply the intervention for the duration of study MCI: Diagnosis of MCI along international criteria, with a predominant amnestic presentation (single- or multi-domain amnestic MCI) MCI: Presence of a cohabitant person who could assist with the application MCI: Ability to apply the intervention for the duration of study, with assistance of co-habitant if needed PD and MCI: Age above 18 years Informed consent as documented by signature Stable home situation (e.g. long-term place to live) that allows for reliable application of intervention for the duration of the study Sufficient German language comprehension to follow the study procedures and answer all questions related to the study outcomes Dosing of dopaminergic, cholinergic, and other PD or MCI medication must have been stable for at least 14 days prior to start of the first intervention Negative pregnancy test during screening (except in women who are surgically sterilized/hysterectomized or postmenopausal for longer than 1 year) Exclusion Criteria: PD: Presence of neurologic, psychiatric, or sleep disorders (others than associated with PD) PD: Parkinsonism without response to levodopa; Atypical Parkinsonian syndromes PD: Cognitive impairment (Montréal Cognitive Assessment [MoCA] <24) MCI: Present diagnosis of a neurological (other than MCI) or interfering psychiatric disease or sleep disorder (e.g. sleep apnoea syndrome, restless legs syndrome) PD and MCI: Severe medical conditions as renal insufficiency, liver failure or congestive heart failure Regular use of the following drugs: Benzodiazepines and other central nervous system (CNS)-depressant substances, melatonin and other sleep inducing substances, approved drugs for Alzheimer-type dementia (acetylcholine-esterase inhibitor, memantine) Inability to hear the tones produced by the TSB Axo Skin disorders/problems/allergies in face/ear area that could worsen with electrode application Known or suspected drug- or medication abuse Known or suspected non-compliance Participation in another study with investigational drug or investigational medical devices within the 30 days preceding and during the present study Previous enrolment in the current study Enrolment of the investigator, his/her family members, employees and other dependent persons Shift work (work during the night) Travelling more than 2 time zones in the last month before intervention starts or during intervention (start of intervention will be adapted to fit with this criteria) 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) Implanted deep brain stimulation electrodes Women who are pregnant or breast feeding Intention to become pregnant during the course of the study Lack of safe contraception, defined as: Female patients of childbearing potential, not using and not willing to continue using a medically reliable method of contraception for the entire study duration, such as oral, injectable, or implantable contraceptives, or intrauterine contraceptive devices, or who are not using any other method considered sufficiently reliable by the investigator in individual cases
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jana Horlacher, MD
Phone
+41432535022
Email
jana.horlacher@usz.ch
First Name & Middle Initial & Last Name or Official Title & Degree
Angelina Maric, PhD
Phone
+41442558615
Email
angelina.maric@usz.ch
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Angelina Maric, PhD
Organizational Affiliation
University of Zurich
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Hospital Zurich, Neurology department
City
Zurich
ZIP/Postal Code
8050
Country
Switzerland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jana Horlacher, MD
Phone
+41432535022
Email
jana.horlacher@usz.ch
First Name & Middle Initial & Last Name & Degree
Angelina Maric, PhD
Phone
+41442558615
Email
Angelina.maric@usz.ch

12. IPD Sharing Statement

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Auditory Slow Wave Enhancement in Parkinson Disease and Mild Cognitive Impairment

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