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

University of Zurich80 enrolled

Overview

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.

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

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

Conditions

Parkinson Disease REM Sleep Behavior Disorder (iRBD)

Interventions

Tosoo AxoraDEVICE

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.

Tosoo AxoraDEVICE

Auditory stimuli will be delivered during the night through integrated headphones with a portable EEG device in a non-PTAS manner.

Eligibility

Sex: ALL

Medical Language ↔ Plain English

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

Locations (1)

University Hospital Zurich, Neurology Department

Zurich, Canton of Zurich, Switzerland

RECRUITING

Outcomes

Primary Outcomes

Presynaptic Dopaminergic Integrity

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

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

Secondary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

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

Central Contacts

Jana Bünzli, MSc

CONTACT

+41 44 255 10 43 jana.buenzli@usz.ch

Marta Menéndez, Dr. phil.

CONTACT

+41 43 253 69 54 marta.menendezgranda@usz.ch

Data from ClinicalTrials.gov

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