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NCT Number: NCT07355842

Role of Slow Waves in the Progression of Neurodegeneration in Isolated REM Sleep Behavior Disorder

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.

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Key information

Conditions

Parkinson Disease Basal Ganglia Diseases Brain Diseases Central Nervous System Diseases Mental Disorders Movement Disorders Nerve Degeneration Nervous System Diseases Neurodegenerative Diseases Parasomnias Parkinsonian Disorders Pathologic Processes Pathological Conditions, Signs and Symptoms REM Sleep Behavior Disorder REM Sleep Behavior Disorder (iRBD) REM Sleep Parasomnias Sleep Wake Disorders Synucleinopathies

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Tosoo Axora

Device

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)

Primary outcomes

  1. Presynaptic Dopaminergic Integrity

    Time frame: assessed at Baseline Visit and Closeout Visit (after 18 months)

    Striatal dopaminergic function as measured by high-resolution 18F-Fluorodopa (18F-DOPA)-PET imaging.

Secondary outcomes

  1. MDS-UPDRS Part III Score

    Time frame: assessed at each visit (Baseline, after 6 months, after 12 months, after 18 months (Closeout))

    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.

  2. Purdue Pegboard Test Score

    Time frame: assessed at each visit (Baseline, after 6 months, after 12 months, after 18 months (Closeout))

    Manual dexterity and fine motor coordination assessed by total score on the Purdue Pegboard Test.

  3. Alternate Finger Tapping Test

    Time frame: assessed at each visit (Baseline, after 6 months, after 12 months, after 18 months (Closeout))

    Motor speed and coordination assessed by performance on the Alternate Finger Tapping Test.

  4. UPDRS I.1 (subjective cognition)

    Time frame: assessed at each visit (Baseline, after 6 months, after 12 months, after 18 months (Closeout))

    Patient-reported cognitive experiences of daily living assessed by MDS-UPDRS Part I, Item 1.1.

  5. Montreal Cognitive Assessment (MoCA) Score

    Time frame: assessed at each visit (Baseline, after 6 months, after 12 months, after 18 months (Closeout)

    Global cognitive function assessed by MoCA total score.

  6. Trail Making Test Part A

    Time frame: assessed at each visit (Baseline, after 6 months, after 12 months, after 18 months (Closeout))

    Processing speed and attention assessed by time to completion on Trail Making Test Part A.

  7. Trail Making Test Part B

    Time frame: assessed at each visit (Baseline, after 6 months, after 12 months, after 18 months (Closeout))

    Executive function assessed by time to completion on Trail Making Test Part B.

  8. Digit Span Forward

    Time frame: assessed at each visit (Baseline, after 6 months, after 12 months, after 18 months (Closeout))

    Attention assessed by Digit Span Forward from the Wechsler Adult Intelligence Scale.

  9. Digit Span backward

    Time frame: assessed at each visit (Baseline, after 6 months, after 12 months, after 18 months (Closeout))

    Working memory assessed by Digit Span Backward from the Wechsler Adult Intelligence Scale

  10. Stroop Test

    Time frame: assessed at each visit (Baseline, after 6 months, after 12 months, after 18 months (Closeout))

    Executive function and inhibitory control assessed by Stroop Color-Word Test.

  11. Verbal Fluency - Semantic

    Time frame: assessed at each visit (Baseline, after 6 months, after 12 months, after 18 months (Closeout))

    Semantic verbal fluency assessed by category fluency task.

  12. Benton Judgment of Line Orientation (BJLO)

    Time frame: assessed at each visit (Baseline, after 6 months, after 12 months, after 18 months (Closeout))

    Visuospatial function assessed by Benton Judgment of Line Orientation test.

  13. LPS-4 Logical Reasoning

    Time frame: assessed at Baseline Visit and Closeout Visit (after 18 months)

    Logical reasoning assessed by Leistungsprüfsystem subtest 4.

  14. Rey-Taylor Complex Figure Test - Copy

    Time frame: assessed at Baseline Visit and Closeout Visit (after 18 months)

    Visuoconstruction assessed by copy trial of the Rey-Taylor Complex Figure Test.

  15. Rey-Taylor Complex Figure Test - Recall

    Time frame: assessed at Baseline Visit and Closeout Visit (after 18 months)

    Visual memory assessed by delayed recall of the Rey-Taylor Complex Figure Test.

  16. California Verbal Learning Test (CVLT)

    Time frame: assessed at Baseline Visit and Closeout Visit (after 18 months)

    Verbal learning and memory assessed by California Verbal Learning Test.

  17. Verbal Fluency - Phonemic

    Time frame: assessed at Baseline Visit and Closeout Visit (after 18 months)

    Phonemic verbal fluency assessed by letter fluency task.

  18. Boston Naming Test (BNT)

    Time frame: assessed at Baseline Visit and Closeout Visit (after 18 months)

    Naming and language function assessed by Boston Naming Test

  19. WAIS Similarities

    Time frame: assessed at Baseline Visit and Closeout Visit (after 18 months)

    Verbal abstract reasoning assessed by similarities subtest from the Wechsler Adult Intelligence Scale

Other outcomes

  1. Exploratory Outcome: Home Sleep EEG - Sleep Microstructure

    Time frame: Continuous over 18 months

    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.

  2. Exploratory Outcome: Home Sleep EEG - Sleep Macrostructure

    Time frame: Continuous over 18 months

    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.

  3. Exploratory Outcome: MRI

    Time frame: assessed at Baseline Visit and Closeout Visit (after 18 months)

    Neuroanatomical and vascular markers assessed by brain MRI, including structural imaging, phase-contrast imaging, arterial spin labeling, and related sequence

  4. Exploratory Outcome: 18F-DOPA PET - Exploratory Parameters

    Time frame: assessed at Baseline Visit and Closeout Visit (after 18 months)

    Exploratory PET parameters including visual assessment of striatal uptake patterns, influx constant (Ki), and F-DOPA distribution beyond predefined regions of interest

  5. Exploratory Outcome: Psychomotor Vigilance Task (PVT)

    Time frame: assessed at each visit (Baseline, after 6 months, after 12 months, after 18 months (Closeout))

    Sustained attention and reaction time assessed by the Psychomotor Vigilance Task.

  6. Exploratory Outcome: Sustained Attention to Response Task (SART)

    Time frame: assessed at each visit (Baseline, after 6 months, after 12 months, after 18 months (Closeout))

    Vigilance and response inhibition assessed by the Sustained Attention to Response Task.

  7. Exploratory Outcome: Glucose Metabolism

    Time frame: assessed at Baseline Visit and Closeout Visit (after 18 months)

    Glucose metabolism (HbA1c, glycosylated hemoglobin) will be assessed to explore glucose tolerance and control through a simple blood draw.

  8. Exploratory Outcome - Polysomnography - Sleep Architecture

    Time frame: assessed at Baseline Visit and Closeout Visit (after 18 months)

    Sleep macrostructure including total sleep time, sleep efficiency, and sleep stage distribution assessed by in-laboratory polysomnography.

  9. Exploratory Outcome: Polysomnography - REM Sleep Without Atonia

    Time frame: assessed at Baseline and Closeout (18 months)

    REM sleep without atonia (RWA) quantified as percentage of REM sleep with elevated muscle tone on polysomnography.

  10. Exploratory Outcome: Actigraphy - Sleep-Wake Patterns

    Time frame: assessed before/after each visit (Baseline, after 6 months, after 12 months, Closeout (18 months)) for 2 weeks each

    Sleep-wake rhythm including total sleep time, sleep efficiency, and rest-activity patterns assessed by wrist actigraphy over 2-week periods.

  11. Exploratory Outcome: Sleep Diary

    Time frame: Assessed before/after each visit (Baseline, after 6 months, after 12 months, Closeout (18 months)) for 2 weeks each

    Self-reported sleep timing, duration, and quality recorded daily over 2-week periods.

  12. Exploratory Outcome: Sleep Quality- Visual Analog Scale -

    Time frame: assessed before/after each visit (Baseline, after 6 months, after 12 months, Closeout (18 months)) for 2 weeks each

    Subjective sleep quality assessed by Visual Analog Scale.

  13. Exploratory Outcome - Karolinska Sleepiness Scale (KSS)

    Time frame: assessed before/after each visit (Baseline, after 6 months, after 12 months, Closeout (18 months)) for 2 weeks each

    Subjective daytime sleepiness assessed by Karolinska Sleepiness Scale.

  14. Exploratory Outcome: Retinal Nerve Fiber Layer Thickness (RNFL)

    Time frame: assessed at Baseline Visit and Closeout Visit (after 18 months)

    Retinal nerve fiber layer thickness measured by optical coherence tomography (OCT)

  15. Exploratory Outcome: Ganglion Cell-Inner Plexiform Layer Thickness (GCIPL)

    Time frame: assessed at Baseline Visit and Closeout Visit (after 18 months)

    Ganglion cell-inner plexiform layer thickness measured by optical coherence tomography (OCT)

  16. Exploratory Outcome: Macular Vessel Density (MVD)

    Time frame: assessed at Baseline Visit and Closeout Visit (after 18 months)

    Macular vessel density measured by optical coherence tomography angiography (OCT-A)

  17. Exploratory Outcome: Non-Motor Symptoms Scale (NMSS)

    Time frame: assessed at each visit (Baseline, after 6 months, after 12 months, after 18 months (Closeout))

    Non-motor symptom severity and frequency assessed by the Non-Motor Symptoms Scale, a 30-item questionnaire covering nine symptom dimensions

  18. Exploratory Outcome: Epworth Sleepiness Scale (ESS)

    Time frame: assessed at each visit (Baseline, after 6 months, after 12 months, after 18 months (Closeout))

    Daytime sleepiness assessed by the Epworth Sleepiness Scale (8-item self-report questionnaire)

  19. Exploratory Outcome: Parkinson's Disease Sleep Scale-2 (PDSS-2)

    Time frame: assessed at each visit (Baseline, after 6 months, after 12 months, after 18 months (Closeout))

    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.

  20. Exploratory Outcome: Ikelos Rating Scale

    Time frame: assessed at each visit (Baseline, after 6 months, after 12 months, after 18 months (Closeout))

    RBD symptom severity assessed by the Ikelos Rating Scale, evaluating frequency and severity of REM sleep behavior disorder

  21. Exploratory Outcome: Exploratory Outcome: EQ-5D-5L

    Time frame: assessed at each visit (Baseline, after 6 months, after 12 months, after 18 months (Closeout))

    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

  22. Exploratory Outcome: Blood Biomarkers

    Time frame: assessed at Baseline Visit and Closeout Visit (after 18 months)

    Neurodegenerative and inflammatory markers measured in blood, including neurofilament light chain (NfL) and alpha-synuclein

  23. Exploratory Outcome: CSF Biomarkers

    Time frame: assessed at Baseline Visit and Closeout Visit (after 18 months)

    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)

Study contacts

Contact information is provided by the study sponsor or research team.

Jana Bünzli, MSc

CONTACT

[email protected]

+41 44 255 10 43

Marta Menéndez, Dr. phil.

CONTACT

[email protected]

+41 43 253 69 54

Sponsors and collaborators

Lead sponsor

University of Zurich

Other

Collaborators

  • University Hospital, Zürich

Registry information

Acronym: SloW-iRBD

Important dates

Study start
2026
Primary completion
2029
Study completion
2029
First posted
Jan 21, 2026
Registry last updated
Feb 17, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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