Parkinson Disease, REM Sleep Behavior Disorder (iRBD)
Conditions
Keywords
Parkinson, Parkinson disease, Sleep, Neurodegeneration, Auditory stimulation, iRBD, REM sleep behavior disorder
Brief summary
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.
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.
Interventions
DEVICETosoo 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.
Sponsors
University of Zurich
University Hospital, Zürich
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Presynaptic Dopaminergic Integrity | 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
| Measure | Time frame | Description |
|---|---|---|
| MDS-UPDRS Part III Score | 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. |
| Purdue Pegboard Test Score | 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. |
| Alternate Finger Tapping Test | 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. |
| UPDRS I.1 (subjective cognition) | 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. |
| Montreal Cognitive Assessment (MoCA) Score | assessed at each visit (Baseline, after 6 months, after 12 months, after 18 months (Closeout) | Global cognitive function assessed by MoCA total score. |
| Trail Making Test Part A | 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. |
| Trail Making Test Part B | 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. |
| Digit Span Forward | 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. |
| Digit Span backward | 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 |
| Stroop Test | 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. |
| Verbal Fluency - Semantic | assessed at each visit (Baseline, after 6 months, after 12 months, after 18 months (Closeout)) | Semantic verbal fluency assessed by category fluency task. |
| Benton Judgment of Line Orientation (BJLO) | 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. |
| LPS-4 Logical Reasoning | assessed at Baseline Visit and Closeout Visit (after 18 months) | Logical reasoning assessed by Leistungsprüfsystem subtest 4. |
| Rey-Taylor Complex Figure Test - Copy | assessed at Baseline Visit and Closeout Visit (after 18 months) | Visuoconstruction assessed by copy trial of the Rey-Taylor Complex Figure Test. |
| Rey-Taylor Complex Figure Test - Recall | assessed at Baseline Visit and Closeout Visit (after 18 months) | Visual memory assessed by delayed recall of the Rey-Taylor Complex Figure Test. |
| California Verbal Learning Test (CVLT) | assessed at Baseline Visit and Closeout Visit (after 18 months) | Verbal learning and memory assessed by California Verbal Learning Test. |
| Verbal Fluency - Phonemic | assessed at Baseline Visit and Closeout Visit (after 18 months) | Phonemic verbal fluency assessed by letter fluency task. |
| Boston Naming Test (BNT) | assessed at Baseline Visit and Closeout Visit (after 18 months) | Naming and language function assessed by Boston Naming Test |
| WAIS Similarities | assessed at Baseline Visit and Closeout Visit (after 18 months) | Verbal abstract reasoning assessed by similarities subtest from the Wechsler Adult Intelligence Scale |
Countries
Switzerland
Contacts
CONTACTJana Bünzli, MSc
CONTACTMarta Menéndez, Dr. phil.
PRINCIPAL_INVESTIGATORAndreas Luft, Prof. Dr. med.
University of Zurich
Outcome results
None listed