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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

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

NCT ID

NCT04736017

First Posted

January 25, 2021

Last Updated

November 14, 2022

Sponsor

University of Zurich

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

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

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

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

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

Time Frame

assessed before and after each intervention (day 1 and 15 of each intervention)

Title

Executive Function and attention

Description

Time Frame

assessed after each intervention (day 15 of each intervention)

Title

Plasma biomarkers

Description

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

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

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

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

jana.horlacher@usz.ch

First Name & Middle Initial & Last Name or Official Title & Degree

Angelina Maric, PhD

Phone

+41442558615

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

jana.horlacher@usz.ch

First Name & Middle Initial & Last Name & Degree

Angelina Maric, PhD

Phone

+41442558615

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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