MCI-AD, Early Stage Alzheimer's DiseaseNana-HomeNCT07672977
Home-Based Closed-Loop Auditory Stimulation to Enhance Slow-Wave Activity in MCI Due to Alzheimer's Disease: A Proof-of-Concept Study
A study testing Closed-Loop Auditory Stimulation in people with MCI-AD, Early Stage Alzheimer's Disease and Alzheimer s Disease, run by Bitbrain at 1 site in Spain.
Trial 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)… Read more about this study
- Who is it for?
- Ages 50 to 75 years
- Conditions the study is for
- MCI-AD, Early Stage Alzheimer's Disease, Alzheimer s Disease, Mild Cognitive Impairment (MCI) Amnestic
- What is being tested?
- Closed-Loop Auditory Stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteSpain
- Study dates
- 1 Jul 2025to 30 Dec 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 9Show fewer
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
About this study
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.
Read the detailed description
Alzheimer's disease (AD) is characterized by progressive cognitive decline and is preceded by a prodromal stage known as amnestic mild cognitive impairment due to AD (MCI-AD), in which early neurophysiological alterations are detectable. Among these, disruptions in sleep architecture-particularly reductions in slow-wave activity (SWA; ~0.5-4 Hz) and sleep spindle activity (~11-16 Hz)-have been associated with impaired memory consolidation and the progression of AD-related pathophysiological processes.
Closed-loop auditory stimulation during sleep (CLAS) is a non-invasive neuromodulation approach that delivers precisely timed auditory stimuli phase-locked to endogenous slow oscillations, with the aim of enhancing slow-wave activity and associated thalamocortical spindle dynamics. This targeted entrainment of sleep oscillations may improve sleep-dependent neural processes and represents a potential therapeutic strategy in the early stages of AD.
The present study is an open-label, single-arm investigation designed to evaluate the effects of home-based CLAS in patients with biomarker-confirmed amnestic mild cognitive impairment due to Alzheimer's disease (MCI-AD). The intervention is self-administered in the participants' home environment. All participants complete an initial treatment period of 3 months followed by a one-month off-treatment (washout) period to assess persistence of effects. Participants who elect to continue may then enter an optional extension phase consisting of 3 additional months of treatment, followed by a second one-month off-treatment period. The total study duration is approximately 4 months for participants completing the initial phase only, or approximately 8 months for those completing the extension phase.
The primary objective is to assess target engagement, defined as the modulation of NREM sleep electrophysiological activity, with particular focus on slow-wave sleep. More precisely, sustained increases in slow-wave activity across the intervention period will be quantified using the study EEG device during intervention nights.
Secondary objectives include evaluation of adherence to the intervention, usability of the device in the home environment, and safety and tolerability. Exploratory objectives include evaluation of the intervention's effects on clinical, functional, cognitive, and sleep-related outcomes, as well as blood-based biomarkers. Clinical, functional, and cognitive variables will be assessed at three time points: before intervention (baseline, Month 0), at the end of the initial treatment period (Month 3), and, for participants entering the extension phase, at the end of the extended treatment period (Month 7).
Blood biomarkers will be obtained at the following time points: baseline (Month 0), end of the initial treatment period (Month 3), and end of the first washout period (Month 4). Participants entering the extension phase will have two additional blood draws: at the end of the extended treatment period (Month 7) and at the end of the second washout period (Month 8). Sleep metrics, derived from EEG recordings or subjective responses to digitized questionnaires, will be acquired daily using the home-based study device.
This study does not include randomization or a sham control group; all participants receive active treatment during intervention periods. The results are expected to provide evidence on neurophysiological target engagement, feasibility, safety, and the clinical and biological effects of home-based CLAS as a therapeutic strategy in early-stage AD.
- Conditions
- MCI-AD, Early Stage Alzheimer's Disease, Alzheimer s Disease, Mild Cognitive Impairment (MCI) Amnestic, AD, AD-MCI
- Being tested
- Closed-Loop Auditory Stimulation
- Keywords
- closed-loop auditory stimulation, sleep, wearable EEG
- Medical subject headings
- Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Closed-Loop Auditory StimulationDevice
Also called AudiStim
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Device: Closed-Loop Auditory Stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Within-subject difference in spindle activity (spindle occurrence 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 spindle activity across nights throughout the intervention period.
Measured: 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
Average number of intervention nights attempted per week. An intervention night is defined as a night during which the participant initiates use of the technology. Adherence will also be summarized as the proportion of participants achieving an average of at least 4 nights per week.
Measured: 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
Percentage of successful sessions among all attempted sessions. A successful session is defined as one in which the participant correctly sets up the device, the system initializes, and usable physiological data are recorded. Sessions may be unsuccessful due to patient-side factors (e.g., electrode placement errors), device-side factors (e.g., technical malfunction), or both.
Measured: 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
Incidence, severity, and relatedness of adverse events associated with the intervention, including sleep disturbance, discomfort related to auditory stimulation, and any device-related adverse effects. Safety will be assessed continuously and summarized at interim and final analyses.
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jun 2026
- Study start1 Jul 2025
- Primary completion30 Nov 2026 (estimated)
- Study completion30 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MCI-AD, Early Stage Alzheimer's DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Bitbrain
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07672977
- Sponsor's protocol ID
- Nana-Home
- Acronym
- Nana-Home
- Status last verified
- Jun 2026
- First submitted
- 15 Jun 2026
- Last updated
- 29 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Home-Based Closed-Loop Auditory Stimulation to Enhance Slow-Wave Activity in MCI Due to Alzheimer's Disease: A Proof-of-Concept Study
- ClinicalTrials.gov ID
- NCT07672977
- Acronym / sponsor ID
- Nana-Home / Nana-Home
- 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
- Study type
- Interventional
- Recruitment status
- Enrolling by invitation
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- BitbrainIndustry (pharma, biotech, devices)
- Study start
- 1 Jul 2025 (actual)
- Primary completion
- 30 Nov 2026 (estimated)
- Study completion
- 30 Dec 2026 (estimated)
- First posted
- 29 Jun 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Alzheimer's disease (AD) is characterized by progressive cognitive decline and is preceded by a prodromal stage known as amnestic mild cognitive impairment due to AD (MCI-AD), in which early neurophysiological alterations are detectable. Among these, disruptions in sleep architecture-particularly reductions in slow-wave activity (SWA; ~0.5-4 Hz) and sleep spindle activity (~11-16 Hz)-have been associated with impaired memory consolidation and the progression of AD-related pathophysiological processes.
Closed-loop auditory stimulation during sleep (CLAS) is a non-invasive neuromodulation approach that delivers precisely timed auditory stimuli phase-locked to endogenous slow oscillations, with the aim of enhancing slow-wave activity and associated thalamocortical spindle dynamics. This targeted entrainment of sleep oscillations may improve sleep-dependent neural processes and represents a potential therapeutic strategy in the early stages of AD.
The present study is an open-label, single-arm investigation designed to evaluate the effects of home-based CLAS in patients with biomarker-confirmed amnestic mild cognitive impairment due to Alzheimer's disease (MCI-AD). The intervention is self-administered in the participants' home environment. All participants complete an initial treatment period of 3 months followed by a one-month off-treatment (washout) period to assess persistence of effects. Participants who elect to continue may then enter an optional extension phase consisting of 3 additional months of treatment, followed by a second one-month off-treatment period. The total study duration is approximately 4 months for participants completing the initial phase only, or approximately 8 months for those completing the extension phase.
The primary objective is to assess target engagement, defined as the modulation of NREM sleep electrophysiological activity, with particular focus on slow-wave sleep. More precisely, sustained increases in slow-wave activity across the intervention period will be quantified using the study EEG device during intervention nights.
Secondary objectives include evaluation of adherence to the intervention, usability of the device in the home environment, and safety and tolerability. Exploratory objectives include evaluation of the intervention's effects on clinical, functional, cognitive, and sleep-related outcomes, as well as blood-based biomarkers. Clinical, functional, and cognitive variables will be assessed at three time points: before intervention (baseline, Month 0), at the end of the initial treatment period (Month 3), and, for participants entering the extension phase, at the end of the extended treatment period (Month 7).
Blood biomarkers will be obtained at the following time points: baseline (Month 0), end of the initial treatment period (Month 3), and end of the first washout period (Month 4). Participants entering the extension phase will have two additional blood draws: at the end of the extended treatment period (Month 7) and at the end of the second washout period (Month 8). Sleep metrics, derived from EEG recordings or subjective responses to digitized questionnaires, will be acquired daily using the home-based study device.
This study does not include randomization or a sham control group; all participants receive active treatment during intervention periods. The results are expected to provide evidence on neurophysiological target engagement, feasibility, safety, and the clinical and biological effects of home-based CLAS as a therapeutic strategy in early-stage AD.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Auditory Stimulation Intervention Group | Experimental | Device: Closed-Loop Auditory StimulationParticipants 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. |
Who may qualify
- Ages
- 50 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Closed-Loop Auditory StimulationAlso: AudiStimThe 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. | Device | Auditory Stimulation Intervention Group |
Primary outcome
Target Engagement: Sustained Increase in Slow-Wave Activity During N2-N3 Sleep
Time frame: 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).
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.
4 secondary outcomes
Sustained Increase in Spindle Activity During N2-N3 Sleep
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jun 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Closed-Loop Auditory Stimulation in people with MCI-AD, Early Stage Alzheimer's Disease and Alzheimer s Disease, run by Bitbrain at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: enrolling by invitation, as of the sponsor's last update on 29 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Target Engagement: Sustained Increase in Slow-Wave Activity During N2-N3 Sleep (time frame: 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).). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jun 2026.