Clinical trial NCT04736017: Auditory Slow Wave Enhancement in Parkinson Disease and Mild Cognitive Impairment
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
Overall status: UNKNOWN
Phase: NA
Conditions: Parkinson Disease
Mild Cognitive Impairment
Keywords: Parkinson Disease
Mild Cognitive Impairment
Excessive Daytime Sleepiness
Sleep
Slow wave sleep
Auditory enhancement
Neurodegeneration
Cognition
Lead sponsor: University of Zurich
Sponsor class: OTHER
First posted: 2021-02-03
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: The study is a randomized, double-blind, sham-controlled cross-over trial.
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Difference in objective EDS
timeFrame: assessed after each intervention (day 15 of each intervention)
measure: Difference in verbal episodic memory performance
timeFrame: assessed after each intervention (day 15 of each intervention)
Secondary outcomes:
measure: Subjective EDS
timeFrame: assessed before and after each intervention (day 1 and 15 of each intervention)
measure: Sustained attention
timeFrame: assessed after each intervention (day 15 of each intervention)
measure: Vigilance
timeFrame: assessed after each intervention (day 15 of each intervention)
measure: Subjective nocturnal sleep quality
timeFrame: assessed before and after each intervention (day 1 and 15 of each intervention)
measure: Executive Function and attention
timeFrame: assessed after each intervention (day 15 of each intervention)
measure: Plasma biomarkers
timeFrame: assessed after each intervention (day 15 of each intervention)
measure: Subjective sleep quality
timeFrame: assessed every morning during the intervention period (days 1-15 of each intervention)
measure: Subjective mood
timeFrame: assessed every evening during the intervention period (days 1-14 of each intervention)
measure: Subjective momentary sleepiness
timeFrame: assessed every evening during the intervention period (days 1-14 of each intervention)
measure: Digital biomarkers
timeFrame: assessed every day during the intervention (days 1-15 of each intervention)
measure: Sleep intensity
timeFrame: assessed continuously during the intervention period (days 1-15 of each intervention)
measure: Depressive symptoms
timeFrame: assessed before and after each intervention (day 1 and 15 of each intervention)
measure: Verbal episodic and visuospatial memory function
timeFrame: assessed after each intervention (day 15 of each intervention)
measure: Quality of life (VAS)
timeFrame: assessed before and after each intervention (day 1 and 14, day 29 and 42)
measure: Motor symptoms
timeFrame: assessed before and after each intervention, in the morning prior to dopaminergic medication intake (day 1 and 14 of each intervention)
measure: Focused motor assessment
timeFrame: assessed on day 4 of each intervention
measure: Overnight memory consolidation
timeFrame: assessed in the evening of day 13 and in the morning of day 14
measure: Overnight restoration inhibitory control
timeFrame: assessed in the evening of day 13 and in the morning of day 14
measure: Overnight restoration working memory
timeFrame: assessed in the evening of day 13 and in the morning of day 14
measure: Overnight restoration vigilance
timeFrame: assessed in the evening of day 13 and in the morning of day 14
Other outcomes:
Locations:
city: Zurich
country: Switzerland
facility: University Hospital Zurich, Neurology department
Study officials:
affiliation: University of Zurich
name: Angelina Maric, PhD
role: PRINCIPAL_INVESTIGATOR
References: