Effects of Real vs. Soundless Acoustic Stimulation During Deep Sleep on Brain Activity, Memory, and Blood Biomarkers in Older Adults (60-85) With Mild Memory Impairment

NCT ID: NCT06669546

Last Updated: 2025-03-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-02-21

Study Completion Date

2028-12-31

Brief Summary

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This study aims to explore a non-invasive way to improve memory and slow cognitive decline in older adults by enhancing sleep quality. Dementia, a leading cause of death worldwide, is often associated with disturbed sleep, particularly the loss of deep, slow-wave sleep (SWS). SWS is important for memory and clearing waste from the brain. Poor SWS can worsen memory loss and allow harmful waste to build up, which may increase the risk of dementia.

The investigators are testing whether phase-locked auditory stimulation (PLAS) can improve SWS in people at a mild stage of cognitive impairment. PLAS uses short sounds played at specific moments to strengthen slow-wave brain activity during sleep. The investigators previous laboratory based research has shown that this can improve memory and help with clearing waste from the brain. Now, the investigators want to test this in a real-world setting, over a longer period, which is unfeasible in a laboratory setting.

In this study, 60 older adults will use home-use devices that deliver either real or sham (soundless) PLAS across two different 4-week periods. Memory will be tested using engaging "serious games." Before and after each experimental period, blood samples will be taken to measure dementia-related markers, and cognitive batteries will be performed. The investigators expect that PLAS will improve sleep, and that this will have a downstream effect on memory and brain clearance, potentially slowing the process of cognitive decline.

If successful, this could lead to the development of an affordable treatment that helps people maintain brain health and prevent dementia.

Detailed Description

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Conditions

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Cognitive Decline Alzheimer Disease Subjective Cognitive Decline (SCD) Mild Cognitive Impairment (MCI) Cognitive Impairment, Mild

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

PREVENTION

Blinding Strategy

SINGLE

Participants

Study Groups

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PLAS first, sham second

In this study arm, participants will undergo a 4-week intervention period with real phase-locked auditory stimulation (PLAS) administered on nights from Monday to Friday. Following this initial intervention period, participants will have a 2-week washout phase. Finally, participants will enter the second intervention period, during which sham (soundless) PLAS will be administered.

Group Type EXPERIMENTAL

Phase-locked auditory stimulation (PLAS)

Intervention Type OTHER

Intervention: Verum Phase-Locked Auditory Stimulation (PLAS) Using the SleepLoop Device.

The experimental intervention utilizes the SleepLoop device, a home-use, EEG-based system designed for phase-locked acoustic stimulation (PLAS). The device continuously monitors sleep through EEG (Fpz) alongside electrooculogram (EOG) and electromyogram (EMG) channels. The device employs a closed-loop algorithm that detects slow oscillations (SOs) in the EEG and delivers short sound stimuli (50 ms pink noise) during the positive half-waves of slow waves in slow-wave sleep (SWS). These stimuli are delivered through integrated headphones in the SleepLoop device. The intervention is applied during work days for 4 weeks. The algorithm is only active during SWS and does not deliver stimuli when the participant is awake, or in lighter sleep stages (N1, N2) or REM sleep. The intensity and algorithm sensitivity are individually calibrated for each participant to optimize stimulation.

Sham Phase-Locked Auditory Stimulation

Intervention Type OTHER

Participants will undergo the same procedure as the real Phase-Locked Auditory Stimulation (PLAS) intervention. However, during the sham condition, the headphones are turned off, and no auditory stimulation is delivered.

Sham first, PLAS second

In this study arm, participants will undergo a 4-week intervention period with sham (soundless) phase-locked auditory stimulation (PLAS) administered on nights from Monday to Friday. Following this initial intervention period, participants will have a 2-week washout phase. Finally, participants will enter the second intervention period, during which real PLAS will be administered.

Group Type EXPERIMENTAL

Phase-locked auditory stimulation (PLAS)

Intervention Type OTHER

Intervention: Verum Phase-Locked Auditory Stimulation (PLAS) Using the SleepLoop Device.

The experimental intervention utilizes the SleepLoop device, a home-use, EEG-based system designed for phase-locked acoustic stimulation (PLAS). The device continuously monitors sleep through EEG (Fpz) alongside electrooculogram (EOG) and electromyogram (EMG) channels. The device employs a closed-loop algorithm that detects slow oscillations (SOs) in the EEG and delivers short sound stimuli (50 ms pink noise) during the positive half-waves of slow waves in slow-wave sleep (SWS). These stimuli are delivered through integrated headphones in the SleepLoop device. The intervention is applied during work days for 4 weeks. The algorithm is only active during SWS and does not deliver stimuli when the participant is awake, or in lighter sleep stages (N1, N2) or REM sleep. The intensity and algorithm sensitivity are individually calibrated for each participant to optimize stimulation.

Sham Phase-Locked Auditory Stimulation

Intervention Type OTHER

Participants will undergo the same procedure as the real Phase-Locked Auditory Stimulation (PLAS) intervention. However, during the sham condition, the headphones are turned off, and no auditory stimulation is delivered.

Interventions

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Phase-locked auditory stimulation (PLAS)

Intervention: Verum Phase-Locked Auditory Stimulation (PLAS) Using the SleepLoop Device.

The experimental intervention utilizes the SleepLoop device, a home-use, EEG-based system designed for phase-locked acoustic stimulation (PLAS). The device continuously monitors sleep through EEG (Fpz) alongside electrooculogram (EOG) and electromyogram (EMG) channels. The device employs a closed-loop algorithm that detects slow oscillations (SOs) in the EEG and delivers short sound stimuli (50 ms pink noise) during the positive half-waves of slow waves in slow-wave sleep (SWS). These stimuli are delivered through integrated headphones in the SleepLoop device. The intervention is applied during work days for 4 weeks. The algorithm is only active during SWS and does not deliver stimuli when the participant is awake, or in lighter sleep stages (N1, N2) or REM sleep. The intensity and algorithm sensitivity are individually calibrated for each participant to optimize stimulation.

Intervention Type OTHER

Sham Phase-Locked Auditory Stimulation

Participants will undergo the same procedure as the real Phase-Locked Auditory Stimulation (PLAS) intervention. However, during the sham condition, the headphones are turned off, and no auditory stimulation is delivered.

Intervention Type OTHER

Other Intervention Names

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Acoustic stimulation Phase-targeted auditory stimulation (PTAS) Auditory stimulation Closed-loop acoustic stimulation

Eligibility Criteria

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Inclusion Criteria

* Written informed consent
* Age between 60 and 85 years
* Cognitive impairment (subjective and/or MoCA between 23-26)
* Native German speakers or comparably fluent
* Normal or corrected-to-normal vision.
* Intact hearing
* A close cohabitant (partner/sibling) should be present to support participants in using study materials/devices.

Exclusion Criteria

* Insomnia assessed by the Regensburg Insomnia Scale (RIS; Crönlein et al., 2013)
* Restless leg syndrome assessed by questions concerning typical symptoms.
* Sleep apnoea assessed by the Berlin Questionnaire (BQ; Netzer et al., 1999)
* Severely irregular sleep patterns assessed by the RIS and the Pittsburgh sleep quality index (PSQI; Buysse et al., 1989)
* Symptoms of depression (Geriatric Depression Scale (GDS; Yesavage et al., 1982) ≥ 5)
* History of untreated severe neurological and psychiatric diseases
* Alcohol or substance abuse
* Use of medication acting on the central nervous system
Minimum Eligible Age

60 Years

Maximum Eligible Age

85 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Zurich

OTHER

Sponsor Role collaborator

Amsterdam University Medical Centers (UMC), Location Academic Medical Center (AMC)

OTHER

Sponsor Role collaborator

University of Bern

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Marc A Züst, PhD

Role: PRINCIPAL_INVESTIGATOR

University Hospital of Old Age Psychiatry and Psychotherapy, University of Bern, 3000 Bern, Switzerland

Locations

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University Hospital of Old Age Psychiatry and Psychotherapy, University of Bern

Bern, , Switzerland

Site Status RECRUITING

Countries

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Switzerland

Central Contacts

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Marc A Züst, PhD

Role: CONTACT

+41 (0)58 630 95 02

Korian Wicki, Master

Role: CONTACT

+41 76 605 24 00

Facility Contacts

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Korian Wicki, Master

Role: primary

+ 41 (0)58 630 68 77

Marina Wunderlin, PhD

Role: backup

+41 (0)31 932 87 07

References

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Lustenberger C, Ferster ML, Huwiler S, Brogli L, Werth E, Huber R, Karlen W. Auditory deep sleep stimulation in older adults at home: a randomized crossover trial. Commun Med (Lond). 2022 Apr 4;2:30. doi: 10.1038/s43856-022-00096-6. eCollection 2022.

Reference Type BACKGROUND
PMID: 35603302 (View on PubMed)

Wunderlin M, Zust MA, Hertenstein E, Feher KD, Schneider CL, Kloppel S, Nissen C. Modulating overnight memory consolidation by acoustic stimulation during slow-wave sleep: a systematic review and meta-analysis. Sleep. 2021 Jul 9;44(7):zsaa296. doi: 10.1093/sleep/zsaa296.

Reference Type BACKGROUND
PMID: 33406249 (View on PubMed)

Zeller CJ, Wunderlin M, Wicki K, Teunissen CE, Nissen C, Zust MA, Kloppel S. Multi-night acoustic stimulation is associated with better sleep, amyloid dynamics, and memory in older adults with cognitive impairment. Geroscience. 2024 Dec;46(6):6157-6172. doi: 10.1007/s11357-024-01195-z. Epub 2024 May 14.

Reference Type BACKGROUND
PMID: 38744792 (View on PubMed)

Wunderlin M, Zeller CJ, Senti SR, Feher KD, Suppiger D, Wyss P, Koenig T, Teunissen CE, Nissen C, Kloppel S, Zust MA. Acoustic stimulation during sleep predicts long-lasting increases in memory performance and beneficial amyloid response in older adults. Age Ageing. 2023 Dec 1;52(12):afad228. doi: 10.1093/ageing/afad228.

Reference Type BACKGROUND
PMID: 38163288 (View on PubMed)

Related Links

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https://www.memory-clinic-bern.ch/aktuelle-studien/schlafstudie/

Information on current sleep studies at the Memory Clinic Bern, focused on research related to sleep and cognitive function.

Other Identifiers

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215333

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

2024-00409

Identifier Type: -

Identifier Source: org_study_id

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