Role of Slow Waves in the Progression of Neurodegeneration in Isolated REM Sleep Behavior Disorder (SloW-iRBD)

This study tests whether enhancing deep sleep with gentle sounds at night can slow progression in people with iRBD or early Parkinson's disease. Participants wear a sensor headband and headphones for 18 months. Four assessments including mobility, memory, imaging (PET/MRI), lumbar puncture, and blood tests are assessed.

Study Overview

• Status: Recruiting
• Conditions: Parkinson Disease; REM Sleep Behavior Disorder (iRBD)
• Intervention / Treatment: Device: Tosoo Axora; Device: Tosoo Axora

Detailed Description

Many people with REM sleep behavior disorder (iRBD) develop Parkinson's disease or similar conditions over the years. To date, there is no effective method to prevent this transition. Animal experiments and observational studies in patients and older adults indicate that deeper sleep is associated with a slower progression of brain changes. In this study, we are now investigating whether enhancement of deep sleep using sounds during sleep can influence the progressive brain changes in iRBD or early Parkinson's disease.

Participants wear a headband with sensors and headphones for 18 months, which plays gentle sounds during sleep to enhance deep sleep. In addition, four examinations are carried out, including tests of mobility, memory, imaging (PET/MRI), a lumbar puncture, and blood sampling. Two of the examinations will take place at the University Hospital of Zurich, and two more can also be carried out at home if desired.

The aim is to investigate whether enhancement of deep sleep can help slow the progression of iRBD or early-stage Parkinson's disease. The study is double-blind and controlled, which means that neither the participants nor the researchers know who is receiving the active treatment.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jana Bünzli, MSc; Phone Number: +41 44 255 10 43; Email: jana.buenzli@usz.ch
• Study Contact Backup: Name: Marta Menéndez, Dr. phil.; Phone Number: +41 43 253 69 54; Email: marta.menendezgranda@usz.ch

Study Locations

• Switzerland
  • Canton of Zurich
    • Zurich, Canton of Zurich, Switzerland, 8091
      • Recruiting
      • University Hospital Zurich, Neurology Department
      • Contact: Angelina Maric, Dr. phil.; Phone Number: +41 255 86 15; Email: angelina.maric@usz.ch
      • Contact: Jana Bünzli, MSc; Phone Number: +41 44 255 10 43; Email: jana.buenzli@usz.ch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Signed informed consent
• Diagnosis of polysomnography-confirmed isolated REM Sleep Behavior Disorder (iRBD) based on international criteria (ICSD-3), combined with EITHER
• UPDRS III without action tremor ≥ 4 AND abnormal olfaction, OR
• diagnosis of PD along international criteria for less than 2 years

Further inclusion criteria are:

• no dopaminergic treatment and no foreseen start of such treatment during duration of the study
• ability to apply the intervention, alone or with help of a co-habitant, stable living situation
• sufficient language skills in German, French or Italian
• negative pregnancy test for women of child-bearing potential

Exclusion Criteria:

• Suspected or known non-compliance to other therapies
• current or recent participation in another clinical trial
• extended absences
• hearing impairment that prevents hearing the tones for auditory stimulation
• non-responder to auditory stimulation during screening
• clinically significant concomitant disease or unstable condition
• Apnea-Hypopnea-Index (AHI) > 15/h or under Continuous Positive Airway Pressure (CPAP) treatment
• Restless Legs Syndrome
• meeting criteria for diagnosis of atypical Parkinson syndrome
• diagnosis of Dementia or Montreal Cognitive Assessment (MoCA) < 24
• severe Depression or other psychiatric disorder
• regular use of benzodiazepines and other central nervous system depressant substances
• current or recent history within the last year of substance abuse disorders or chronic alcohol consumption
• recent or planned major surgery
• history of allergies and hypersensitivity relevant for electrode application or medication allergies
• additional exclusion criteria for PET imaging
• any criterion that may pose the participant at risk
• breastfeeding, intention to become pregnant, or unwillingness to use medically reliable contraception for women of child-bearing potential

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Verum arm; Nightly enhancement of slow waves through Phase Targeted Auditory Stimulation (PTAS) over 18 months.	Device: Tosoo Axora; Phase Targeted Auditory Stimulation (PTAS) will be applied through integrated headphones with a portable EEG device when non-rapid-eye-movement (NREM) sleep is detected during the night.; Other Names: PTAS Intervention (Verum); Device: Tosoo Axora; Auditory stimuli will be delivered during the night through integrated headphones with a portable EEG device in a non-PTAS manner.; Other Names: PTAS Intervention (Sham)
Sham Comparator: Sham arm; Nightly application of tones that will be applied in a non-PTAS manner, resulting in no enhancement of slow waves over 18 months.	Device: Tosoo Axora; Phase Targeted Auditory Stimulation (PTAS) will be applied through integrated headphones with a portable EEG device when non-rapid-eye-movement (NREM) sleep is detected during the night.; Other Names: PTAS Intervention (Verum); Device: Tosoo Axora; Auditory stimuli will be delivered during the night through integrated headphones with a portable EEG device in a non-PTAS manner.; Other Names: PTAS Intervention (Sham)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Presynaptic Dopaminergic Integrity	Striatal dopaminergic function as measured by high-resolution 18F-Fluorodopa (18F-DOPA)-PET imaging.	assessed at Baseline Visit and Closeout Visit (after 18 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MDS-UPDRS Part III Score	Motor symptom severity assessed by the Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS III), a clinician-rated examination of motor signs.	assessed at each visit (Baseline, after 6 months, after 12 months, after 18 months (Closeout))
Purdue Pegboard Test Score	Manual dexterity and fine motor coordination assessed by total score on the Purdue Pegboard Test.	assessed at each visit (Baseline, after 6 months, after 12 months, after 18 months (Closeout))
Alternate Finger Tapping Test	Motor speed and coordination assessed by performance on the Alternate Finger Tapping Test.	assessed at each visit (Baseline, after 6 months, after 12 months, after 18 months (Closeout))
UPDRS I.1 (subjective cognition)	Patient-reported cognitive experiences of daily living assessed by MDS-UPDRS Part I, Item 1.1.	assessed at each visit (Baseline, after 6 months, after 12 months, after 18 months (Closeout))
Montreal Cognitive Assessment (MoCA) Score	Global cognitive function assessed by MoCA total score.	assessed at each visit (Baseline, after 6 months, after 12 months, after 18 months (Closeout)
Trail Making Test Part A	Processing speed and attention assessed by time to completion on Trail Making Test Part A.	assessed at each visit (Baseline, after 6 months, after 12 months, after 18 months (Closeout))
Trail Making Test Part B	Executive function assessed by time to completion on Trail Making Test Part B.	assessed at each visit (Baseline, after 6 months, after 12 months, after 18 months (Closeout))
Digit Span Forward	Attention assessed by Digit Span Forward from the Wechsler Adult Intelligence Scale.	assessed at each visit (Baseline, after 6 months, after 12 months, after 18 months (Closeout))
Digit Span backward	Working memory assessed by Digit Span Backward from the Wechsler Adult Intelligence Scale	assessed at each visit (Baseline, after 6 months, after 12 months, after 18 months (Closeout))
Stroop Test	Executive function and inhibitory control assessed by Stroop Color-Word Test.	assessed at each visit (Baseline, after 6 months, after 12 months, after 18 months (Closeout))
Verbal Fluency - Semantic	Semantic verbal fluency assessed by category fluency task.	assessed at each visit (Baseline, after 6 months, after 12 months, after 18 months (Closeout))
Benton Judgment of Line Orientation (BJLO)	Visuospatial function assessed by Benton Judgment of Line Orientation test.	assessed at each visit (Baseline, after 6 months, after 12 months, after 18 months (Closeout))
LPS-4 Logical Reasoning	Logical reasoning assessed by Leistungsprüfsystem subtest 4.	assessed at Baseline Visit and Closeout Visit (after 18 months)
Rey-Taylor Complex Figure Test - Copy	Visuoconstruction assessed by copy trial of the Rey-Taylor Complex Figure Test.	assessed at Baseline Visit and Closeout Visit (after 18 months)
Rey-Taylor Complex Figure Test - Recall	Visual memory assessed by delayed recall of the Rey-Taylor Complex Figure Test.	assessed at Baseline Visit and Closeout Visit (after 18 months)
California Verbal Learning Test (CVLT)	Verbal learning and memory assessed by California Verbal Learning Test.	assessed at Baseline Visit and Closeout Visit (after 18 months)
Verbal Fluency - Phonemic	Phonemic verbal fluency assessed by letter fluency task.	assessed at Baseline Visit and Closeout Visit (after 18 months)
Boston Naming Test (BNT)	Naming and language function assessed by Boston Naming Test	assessed at Baseline Visit and Closeout Visit (after 18 months)
WAIS Similarities	Verbal abstract reasoning assessed by similarities subtest from the Wechsler Adult Intelligence Scale	assessed at Baseline Visit and Closeout Visit (after 18 months)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory Outcome: Home Sleep EEG - Sleep Microstructure	NREM sleep oscillatory activity and microstructural features measured by portable EEG device (Tosoo Axora) during nightly use, including but not limited to slow wave activity, sleep spindles, and their temporal dynamics.	Continuous over 18 months
Exploratory Outcome: Home Sleep EEG - Sleep Macrostructure	Sleep architecture and derived metrics measured by portable EEG device (Tosoo Axora) during nightly use, including sleep stage distribution, sleep continuity, and sleep timing parameters.	Continuous over 18 months
Exploratory Outcome: MRI	Neuroanatomical and vascular markers assessed by brain MRI, including structural imaging, phase-contrast imaging, arterial spin labeling, and related sequence	assessed at Baseline Visit and Closeout Visit (after 18 months)
Exploratory Outcome: 18F-DOPA PET - Exploratory Parameters	Exploratory PET parameters including visual assessment of striatal uptake patterns, influx constant (Ki), and F-DOPA distribution beyond predefined regions of interest	assessed at Baseline Visit and Closeout Visit (after 18 months)
Exploratory Outcome: Psychomotor Vigilance Task (PVT)	Sustained attention and reaction time assessed by the Psychomotor Vigilance Task.	assessed at each visit (Baseline, after 6 months, after 12 months, after 18 months (Closeout))
Exploratory Outcome: Sustained Attention to Response Task (SART)	Vigilance and response inhibition assessed by the Sustained Attention to Response Task.	assessed at each visit (Baseline, after 6 months, after 12 months, after 18 months (Closeout))
Exploratory Outcome: Glucose Metabolism	Glucose metabolism (HbA1c, glycosylated hemoglobin) will be assessed to explore glucose tolerance and control through a simple blood draw.	assessed at Baseline Visit and Closeout Visit (after 18 months)
Exploratory Outcome - Polysomnography - Sleep Architecture	Sleep macrostructure including total sleep time, sleep efficiency, and sleep stage distribution assessed by in-laboratory polysomnography.	assessed at Baseline Visit and Closeout Visit (after 18 months)
Exploratory Outcome: Polysomnography - REM Sleep Without Atonia	REM sleep without atonia (RWA) quantified as percentage of REM sleep with elevated muscle tone on polysomnography.	assessed at Baseline and Closeout (18 months)
Exploratory Outcome: Actigraphy - Sleep-Wake Patterns	Sleep-wake rhythm including total sleep time, sleep efficiency, and rest-activity patterns assessed by wrist actigraphy over 2-week periods.	assessed before/after each visit (Baseline, after 6 months, after 12 months, Closeout (18 months)) for 2 weeks each
Exploratory Outcome: Sleep Diary	Self-reported sleep timing, duration, and quality recorded daily over 2-week periods.	Assessed before/after each visit (Baseline, after 6 months, after 12 months, Closeout (18 months)) for 2 weeks each
Exploratory Outcome: Sleep Quality- Visual Analog Scale -	Subjective sleep quality assessed by Visual Analog Scale.	assessed before/after each visit (Baseline, after 6 months, after 12 months, Closeout (18 months)) for 2 weeks each
Exploratory Outcome - Karolinska Sleepiness Scale (KSS)	Subjective daytime sleepiness assessed by Karolinska Sleepiness Scale.	assessed before/after each visit (Baseline, after 6 months, after 12 months, Closeout (18 months)) for 2 weeks each
Exploratory Outcome: Retinal Nerve Fiber Layer Thickness (RNFL)	Retinal nerve fiber layer thickness measured by optical coherence tomography (OCT)	assessed at Baseline Visit and Closeout Visit (after 18 months)
Exploratory Outcome: Ganglion Cell-Inner Plexiform Layer Thickness (GCIPL)	Ganglion cell-inner plexiform layer thickness measured by optical coherence tomography (OCT)	assessed at Baseline Visit and Closeout Visit (after 18 months)
Exploratory Outcome: Macular Vessel Density (MVD)	Macular vessel density measured by optical coherence tomography angiography (OCT-A)	assessed at Baseline Visit and Closeout Visit (after 18 months)
Exploratory Outcome: Non-Motor Symptoms Scale (NMSS)	Non-motor symptom severity and frequency assessed by the Non-Motor Symptoms Scale, a 30-item questionnaire covering nine symptom dimensions	assessed at each visit (Baseline, after 6 months, after 12 months, after 18 months (Closeout))
Exploratory Outcome: Epworth Sleepiness Scale (ESS)	Daytime sleepiness assessed by the Epworth Sleepiness Scale (8-item self-report questionnaire)	assessed at each visit (Baseline, after 6 months, after 12 months, after 18 months (Closeout))
Exploratory Outcome: Parkinson's Disease Sleep Scale-2 (PDSS-2)	Sleep disturbances assessed by the PDSS-2, a 15-item self-administered questionnaire covering motor problems at night, PD-specific nocturnal symptoms, and disturbed sleep.	assessed at each visit (Baseline, after 6 months, after 12 months, after 18 months (Closeout))
Exploratory Outcome: Ikelos Rating Scale	RBD symptom severity assessed by the Ikelos Rating Scale, evaluating frequency and severity of REM sleep behavior disorder	assessed at each visit (Baseline, after 6 months, after 12 months, after 18 months (Closeout))
Exploratory Outcome: Exploratory Outcome: EQ-5D-5L	Health-related quality of life assessed by the EQ-5D-5L questionnaire, covering mobility, self-care, usual activities, pain/discomfort, and anxiety/depression, plus visual analogue scale	assessed at each visit (Baseline, after 6 months, after 12 months, after 18 months (Closeout))
Exploratory Outcome: Blood Biomarkers	Neurodegenerative and inflammatory markers measured in blood, including neurofilament light chain (NfL) and alpha-synuclein	assessed at Baseline Visit and Closeout Visit (after 18 months)
Exploratory Outcome: CSF Biomarkers	Neurodegenerative and inflammatory markers measured in cerebrospinal fluid, including amyloid-β, tau, alpha-synuclein, and neurofilament light chain (optional, for participants who consent to lumbar puncture)	assessed at Baseline Visit and Closeout Visit (after 18 months)

Collaborators and Investigators

• Sponsor: University of Zurich
• Collaborators: University Hospital, Zürich
• Investigators: Principal Investigator: Andreas Luft, Prof. Dr. med., University of Zurich

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2026
• Primary Completion (Estimated): June 30, 2029
• Study Completion (Estimated): June 30, 2029

Study Registration Dates

• First Submitted: December 22, 2025
• First Submitted That Met QC Criteria: January 20, 2026
• First Posted (Actual): January 21, 2026

Study Record Updates

• Last Update Posted (Actual): February 17, 2026
• Last Update Submitted That Met QC Criteria: February 16, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Parkinson; Sleep; Neurodegeneration; Parkinson disease; Auditory stimulation; REM sleep behavior disorder; iRBD
• Additional Relevant MeSH Terms: Synucleinopathies; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Pathologic Processes; Neurodegenerative Diseases; Sleep Wake Disorders; Movement Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Parasomnias; REM Sleep Parasomnias; Pathological Conditions, Signs and Symptoms; Parkinson Disease; REM Sleep Behavior Disorder; Nerve Degeneration
• Other Study ID Numbers: SloW-iRBD; 2025-D0069 (Other Identifier: BASEC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No