Sleep Stimulation to Enhance Waste Clearance in the Brain

Free University of Brussels (ULB)

Status: Not yet enrolling

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

Treatments: Other: Closed-loop acoustic stimulation

Study type: Interventional

Funder types: Other

Identifiers

NCT07051239

HUB2025028

Details and patient eligibility

About

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.

Enrollment: 105 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

For the positive amyloid load group:

-Participants who meet the criteria of subjective cognitive decline or mild cognitive impairment (Clinical Dementia Rating < 2; Mini-Mental State Examination ≥ 21) and brain amyloid-beta (Aβ) accumulation confirmed by CSF or amyloid-PET, the inclusion age range is 55-80 years.

For healthy groups:

-Inclusion age range is 18-80 years.

Inclusion criteria:

• 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.

Exclusion criteria:

• 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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Single Blind

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105 participants in 6 patient groups

Healthy young, auditory stimulation, then sham

Experimental group

Treatment:

Other: Closed-loop acoustic stimulation

Healthy young, sham, then auditory stimulation

Experimental group

Treatment:

Other: Closed-loop acoustic stimulation

Healthy old, auditory stimulation, then sham

Experimental group

Treatment:

Other: Closed-loop acoustic stimulation

Healthy old, sham then auditory stimulation

Experimental group

Treatment:

Other: Closed-loop acoustic stimulation

Positive amyloid load group, auditory stimulation, then sham

Experimental group

Treatment:

Other: Closed-loop acoustic stimulation

Positive amyloid load group, sham, then auditory stimulation

Experimental group

Treatment:

Other: Closed-loop acoustic stimulation