Sleep Stimulation to Enhance Waste Clearance in the Brain

NCT07051239 | Not Yet Recruiting

• 1 other identifier: HUB2025028
• Study Type: interventional
• Target: 105
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to examine whether multi-night closed-loop auditory stimulation (CLAS) during sleep can enhance waste clearance and memory consolidation in healthy adults and older adults with subjective cognitive decline or mild cognitive impairment who exhibit elevated brain amyloid levels identified through prior clinical screening. Specifically, the study investigates whether sleep stimulation increases the clearance of plasma biomarkers related to neurodegeneration, improves the brain's waste clearance system, and supports memory consolidation. Participants will undergo five nights each of CLAS and sham (no stimulation) interventions, with a washout period in between. They will also complete clinical assessments, including MRI scans, blood sample collection, and cognitive testing, and will keep track of subjective sleep quality, sleepiness, mood, and fatigue throughout the interventions.

Conditions

Healthy; Subjective Cognitive Decline (SCD); Mild Cognitive Impairment (MCI); Alzheimer Disease (AD)

Outcome Measures

Primary Outcomes (1)

• Plasma biomarkers

  Levels of plasma biomarkers associated with neurodegeneration and brain health will be compared between stimulation and sham interventions.

  Blood samples will be collected the morning after each intervention phase. Interventions are separated by one week.

Secondary Outcomes (9)

• Glymphatic function

  MRI scans will be performed the morning after each intervention phase. Interventions are separated by one week.

• CLAS evoked responses

  Each night of sleep during each intervention phase, whether receiving stimulation or sham.

• Slow wave activity (SWA)

  Each night of sleep during each intervention phase, whether receiving stimulation or sham.

• Sleep architecture

  Each night of sleep during each intervention phase, whether receiving stimulation or sham.

• Change in memory performance

  Before and after each intervention period. Interventions are separated by one week.

Study Arms (6)

Healthy young, auditory stimulation, then sham

EXPERIMENTAL

Other: Closed-loop acoustic stimulation

Healthy young, sham, then auditory stimulation

EXPERIMENTAL

Other: Closed-loop acoustic stimulation

Healthy old, auditory stimulation, then sham

EXPERIMENTAL

Other: Closed-loop acoustic stimulation

Healthy old, sham then auditory stimulation

EXPERIMENTAL

Other: Closed-loop acoustic stimulation

Positive amyloid load group, auditory stimulation, then sham

EXPERIMENTAL

Other: Closed-loop acoustic stimulation

Positive amyloid load group, sham, then auditory stimulation

EXPERIMENTAL

Other: Closed-loop acoustic stimulation

Interventions

Closed-loop acoustic stimulation OTHER

At-home sleep will be monitored using an EEG headband. Non-awakening auditory stimuli will be delivered during non-rapid eye movement sleep (NREM), timed to the ascending phase of slow waves, using either active or control (sham) conditions.

Healthy old, auditory stimulation, then sham; Healthy old, sham then auditory stimulation; Healthy young, auditory stimulation, then sham; Healthy young, sham, then auditory stimulation; Positive amyloid load group, auditory stimulation, then sham; Positive amyloid load group, sham, then auditory stimulation

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Proficiency in the French language (close to native level) to complete the neuropsychological evaluation and cognitive tests.
• MRI compatibility: absence of metallic materials in the body (implants, vascular clips, certain types of orthopedic material, etc.), a pacemaker or other types of stimulators, cochlear implants, or any other electronic devices.

You may not qualify if:

• Current or past psychiatric or neurological conditions (except for those directly associated with the patient group).
• The presence of severe untreated sleep disorders.
• The presence of irregular sleep-wake cycles (due to shiftwork or extreme chronotype).
• The presence of moderate depression or high levels of anxiety.
• Ongoing treatment with psychotropic medications (benzodiazepines, antidepressants).
• Regular or excessive consumption of alcohol or caffeinated drinks.
• Consumption of other psychoactive substances known to have an impact on the central nervous system.
• Insufficient visual or auditory acuity to complete the assessments if uncorrected. Normal hearing is required for sound stimulation to be effective.
• Claustrophobia that prevents undergoing brain imaging (MRI).
• Pregnancy or currently breastfeeding

Sponsors & Collaborators

• Erasme University Hospital: lead
• University of Amsterdam: collaborator

Study Sites (1)

Hôpital Universitaire de Bruxelles

Brussels, Belgium

Location

MeSH Terms

Conditions

Cognitive Dysfunction; Alzheimer Disease

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases

Study Officials

• Mélanie Strauss, MD, PhD

  Université Libre de Bruxelles

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mélanie Strauss, MD, PhD

CONTACT

+32 2 555 55 39; melanie.strauss@hubruxelles.be

Rebeca Sifuentes Ortega, PhD

CONTACT

rebeca.sifuentes.ortega@ulb.be

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 26, 2025
• First Posted: July 4, 2025
• Study Start: September 1, 2025
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): September 1, 2028
• Last Updated: July 9, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share

Locations

BE (1)