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
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Parkinson Disease
- Sponsor
- University of Zurich
- Enrollment
- 48
- Locations
- 1
- Primary Endpoint
- Difference in objective EDS
- Status
- Recruiting
- Last Updated
- 3 years ago
Overview
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.
Investigators
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
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
Outcomes
Primary Outcomes
Difference in objective EDS
Time Frame: assessed after each intervention (day 15 of each intervention)
Difference in objective excessive daytime sleepiness (EDS), measured with Multiple Sleep Latency Test (MSLT; minutes), in Parkinson patients
Difference in verbal episodic memory performance
Time Frame: assessed after each intervention (day 15 of each intervention)
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 Outcomes
- Subjective nocturnal sleep quality(assessed before and after each intervention (day 1 and 15 of each intervention))
- Executive Function and attention(assessed after each intervention (day 15 of each intervention))
- Subjective sleep quality(assessed every morning during the intervention period (days 1-15 of each intervention))
- Digital biomarkers(assessed every day during the intervention (days 1-15 of each intervention))
- Sleep intensity(assessed continuously during the intervention period (days 1-15 of each intervention))
- Depressive symptoms(assessed before and after each intervention (day 1 and 15 of each intervention))
- Overnight memory consolidation(assessed in the evening of day 13 and in the morning of day 14)
- Overnight restoration working memory(assessed in the evening of day 13 and in the morning of day 14)
- Subjective EDS(assessed before and after each intervention (day 1 and 15 of each intervention))
- Sustained attention(assessed after each intervention (day 15 of each intervention))
- Vigilance(assessed after each intervention (day 15 of each intervention))
- Plasma biomarkers(assessed after each intervention (day 15 of each intervention))
- Subjective mood(assessed every evening during the intervention period (days 1-14 of each intervention))
- Subjective momentary sleepiness(assessed every evening during the intervention period (days 1-14 of each intervention))
- Quality of life (VAS)(assessed before and after each intervention (day 1 and 14, day 29 and 42))
- Verbal episodic and visuospatial memory function(assessed after each intervention (day 15 of each intervention))
- Overnight restoration vigilance(assessed in the evening of day 13 and in the morning of day 14)
- Motor symptoms(assessed before and after each intervention, in the morning prior to dopaminergic medication intake (day 1 and 14 of each intervention))
- Focused motor assessment(assessed on day 4 of each intervention)
- Overnight restoration inhibitory control(assessed in the evening of day 13 and in the morning of day 14)