Home-Based Closed-Loop Auditory Stimulation to Enhance Slow-Wave Activity in MCI Due to Alzheimer's Disease: A Proof-of-Concept Study

NCT07672977 | Enrolling By Invitation

• 1 other identifier: Nana-Home
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This proof-of-concept study explores whether long-term home-based closed-loop auditory stimulation during sleep enhances slow-wave activity (SWA) and yields preliminary efficacy signals in patients with amnestic mild cognitive impairment due to Alzheimer's disease (MCI-AD), confirmed by cerebrospinal fluid (CSF) biomarkers or positron emission tomography (PET). The intervention is self-administered at participants' homes over an initial treatment period of 3 months, followed by a 1-month off-treatment (washout) period. Participants may then enter an optional extension phase consisting of 3 additional months of treatment followed by a second 1-month washout period, for a total study duration of up to 8 months. Participants who complete the Nana-Lab Study (NCT07402590) may be invited to provide informed consent for screening and potential enrollment in this study. All enrolled participants receive nightly active treatment during intervention periods. This study does not include randomization or a sham control group.

Conditions

MCI-AD, Early Stage Alzheimer's Disease; Alzheimer s Disease; Mild Cognitive Impairment (MCI) Amnestic; AD; AD-MCI

Keywords

closed-loop auditory stimulation; sleep; wearable EEG

Outcome Measures

Primary Outcomes (1)

• Target Engagement: Sustained Increase in Slow-Wave Activity During N2-N3 Sleep

  Within-subject difference in mean slow-wave activity during N2-N3 sleep between stimulation and sham conditions, computed nightly and aggregated across the intervention period. The sustained effect will be evaluated as the consistency of the stimulation-induced increase in slow-wave activity across nights throughout the intervention period.

  Assessed at each intervention night, from baseline through the end of the intervention period (3 months, or up to 7 months for participants entering the extension phase).

Secondary Outcomes (4)

• Sustained Increase in Spindle Activity During N2-N3 Sleep

  Assessed at each intervention night, from baseline through the end of the intervention period (3 months, or up to 7 months for participants entering the extension phase).

• Adherence to the Intervention

  Computed as a summary measure over each participant's full intervention period (3 months, or up to 7 months for participants entering the extension phase).

• Usability of the Closed-Loop Auditory Stimulation System

  Computed as a summary measure over each participant's full intervention period (3 months, or up to 7 months for participants entering the extension phase).

• Safety and Tolerability

  Continuously monitored from enrollment through the end of participation, with summary analyses at 3 months and, for participants entering the extension phase, at 7 months.

Other Outcomes (34)

• Cognitive Performance - Alzheimer's Disease Assessment Scale-Cognitive Subscale, 11-item version (ADAS-Cog 11)

  Assessments at baseline (Month 0), end of initial treatment (Month 3), and end of extension treatment (Month 7).

• Functional Ability - Alzheimer's Disease Cooperative Study-Activities of Daily Living scale for Mild Cognitive Impairment (ADCS-ADL-MCI)

  Assessments at baseline (Month 0), end of initial treatment (Month 3), and end of extension treatment (Month 7).

• Global Cognition - MoCA

  Assessments at baseline (Month 0), end of initial treatment (Month 3), and end of extension treatment (Month 7).

Study Arms (1)

Auditory Stimulation Intervention Group

EXPERIMENTAL

Participants receive closed-loop auditory stimulation during sleep at home for an initial treatment period of 3 months, followed by a 1-month off-treatment (washout) period. Participants may then enter an optional extension phase consisting of 3 additional months of treatment followed by a second 1-month washout period.

Device: Closed-Loop Auditory Stimulation

Interventions

Closed-Loop Auditory Stimulation DEVICE

The system delivers brief auditory stimuli (pink noise bursts) that are time-locked to the up-phase of endogenous slow oscillations during non-rapid eye movement (NREM) sleep, as detected in real time using electroencephalography (EEG). Stimulation is withheld in approximately half of detected slow oscillations (Sham) to serve as a within-session control condition for the acute effects of stimulation. The other half of the slow oscillations are stimulated at a volume between 30-60 dB (Stim), which is personalized to the patient and adapts during the night to improve response while reducing awakenings. The objective of the stimulation is to enhance slow-wave activity (SWA) during deep sleep through phase-specific entrainment of endogenous slow-wave activity. The intervention is self-administered using a portable system adapted for use in patients with MCI. Participants are instructed to use the device for as many nights as possible throughout the study period.

Also known as: AudiStim

Auditory Stimulation Intervention Group

Eligibility Criteria

• Age: 50 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age between 50 and 75 years (inclusive).
• Spanish as native language.
• Diagnosis of amnestic mild cognitive impairment due to Alzheimer's disease, confirmed by cerebrospinal fluid biomarkers or amyloid PET.
• Normal or corrected-to-normal color vision (required for completion of visual-analog study assessments).
• Adequate hearing to perceive the auditory stimuli used in the intervention, defined as a hearing threshold of 50 dB or below, assessed during the screening session.

You may not qualify if:

• Severe systemic or complex chronic disease that, in the investigator's judgment, would compromise participant safety or data quality, including but not limited to: advanced heart disease; advanced chronic kidney disease (stage 4 or 5); severe pulmonary disease (e.g., COPD GOLD stage III-IV); metastatic or terminal cancer; severe hematological disorders; or active or uncontrolled chronic infectious disease (e.g., untreated HIV).
• Evidence on neuroimaging of strategic infarcts or other findings that may account for secondary cognitive impairment.
• Alcohol or psychotropic substance abuse.
• Diagnosis of depression or any severe psychiatric disorder within the 5 years prior to evaluation.
• Changes in benzodiazepine or antidepressant treatment within the 6 months prior to baseline evaluation.
• Current treatment with neuroleptics.
• Epilepsy with active treatment within the last 5 years, or any neurological comorbidity that may cause cognitive impairment or structural brain damage.
• Unable to read and write in Spanish.
• Inability to use the study device effectively, as determined during the screening session. This includes, but is not limited to, anatomical or dermatological factors preventing adequate electrode placement, or excessive EEG signal artifacts that prevent reliable detection of sleep oscillations.

Sponsors & Collaborators

• Bitbrain: lead

Study Sites (1)

Bit&Brain Technologies SL

Zaragoza, Zaragoza, 50006, Spain

Location

MeSH Terms

Conditions

Cognitive Dysfunction

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 15, 2026
• First Posted: June 29, 2026
• Study Start: July 1, 2025
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): December 30, 2026
• Last Updated: June 29, 2026

Record last verified: 2026-06

Locations

ES (1)