An interventional study of ATTN201 Focused Ultrasound to the CMN and ATTN201 Unfocused Ultrasound in Alzheimer's Disease (AD), Mild Cognitive Impairment (MCI) and Mild Cognitive Impairment (MCI) Due to Alzheimer's Disease, sponsored by University of California, San Francisco. Not yet recruiting at 1 site in United States. Open to participants aged 65 Years and older. Per ClinicalTrials.gov, last updated 2026-10-08.
Sponsored by University of California, San Francisco · Not applicable, Interventional, and Treatment
The goal of this clinical trial is to learn if a wearable ultrasound device, called ATTN201, is safe and easy to use. The study is for adults ages 65 and older who have mild cognitive impairment (MCI) and a buildup of a protein called amyloid in the brain. Amyloid buildup is an early sign of Alzheimer's disease. The ATTN201 device sends low-intensity sound waves to a deep area of the brain that helps control sleep. The aim is to boost deep-sleep brain waves. These brain waves may help the brain clear away waste, including amyloid.
The main questions it aims to answer are:
Researchers will compare focused ultrasound to unfocused ultrasound. Unfocused ultrasound is a look-alike treatment. It feels and sounds the same but is not aimed at the brain target. The comparison will show if the focused treatment changes sleep brain waves, blood markers of Alzheimer's disease, or memory and thinking.
Participants will:
This pilot study is a randomized, double-blind, parallel-group trial of repeated low-intensity focused ultrasound (LIFU) stimulation of the centromedian nucleus of the thalamus (CMN) in amyloid-positive older adults with mild cognitive impairment (MCI).
Background and rationale: Poor sleep both predicts and accelerates Alzheimer's disease (AD) pathology, in part by impairing glymphatic clearance of metabolites including soluble amyloid-beta and tau. Slow waves during sleep generate metabolic signals that alter neurovascular tone and cerebrospinal fluid (CSF) volume, creating pulsatile fluid flow thought to support clearance. Slow waves can be entrained by stimulating seed regions of the brain at a slow rate, but existing approaches (transcranial magnetic stimulation, optogenetic or electrical stimulation of the CMN) are too invasive, cumbersome, or costly for regular home use in a broad aging population. Low-Intensity focused ultrasound can both elicit neural activity in the CMN and directly produce fluid flow, non-invasively and with lightweight hardware. In a prior single-session study targeting the CMN in 10 patients with chronic pain, sonication improved subjective sleep for several days. This study extends that preliminary work to a clinical population for which the effects are likely to be therapeutically relevant.
Investigational device: ATTN201 is a head-worn LIFU system that delivers MRI-guided stimulation offline, without real-time imaging or clinician aid. Bilateral 64-element sparse ultrasound arrays operating at 500 kHz are positioned over the temporal windows and deliver cross-beam focused stimulation to deep brain targets. Targeting is participant-specific: before first use, each participant undergoes a 3.0T MRI for personalized targeting. Automated brain segmentation, transducer spatial mapping, and acoustic simulation are used to compute the per-element phase delays required to focus energy at the target. All stimulation remains within International Transcranial Ultrasonic Stimulation Safety and Standards (ITRUSST) consortium recommendations, with sessions lasting up to 60 minutes.
Control condition: Unfocused ultrasound is used as the comparator to maintain participant and study-administrator blinding. It mimics the auditory and peripheral sensations of focused stimulation without creating substantive pressure at the focal target relative to surrounding tissue.
Study conduct: Because the study enrolls people with MCI, capacity to consent is assessed before enrollment using a teach-back method, and only individuals who can demonstrate adequate understanding of the study are enrolled. After screening and informed consent, participants complete screening and baseline visits that include a blood draw for plasma biomarkers, cognitive and functional assessment, safety assessments, and an MRI. Participants then complete at least 5 days of at-home baseline sleep recording using actigraphy, sleep diaries, and wearable EEG. They are subsequently randomized to CMN-focused or unfocused stimulation, delivered during 10 nap opportunities over 2 weeks at the study site or the participant's home, per participant preference. Treatment visits include continuous EEG monitoring, adverse event assessment, and visual analog scales for memory and related psychiatric symptoms; home sleep monitoring continues throughout the treatment period. A post-treatment visit repeats the baseline measures, including cognitive testing, neurological exam, blood draw, and an MRI. An optional follow-up visit 3 months later repeats the same measures to assess durability of effects. The study is conducted in conformance with Good Clinical Practice (GCP).
3,678 studies on the registry are indexed under Alzheimer Disease; 872 are open to participants now.
This study's planned enrollment of 28 is below the median of 70 across 2,808 interventional studies indexed under Alzheimer Disease.
Browse Alzheimer Disease studies →University of California, San Francisco is the lead sponsor of 2,133 studies on the registry; 376 are open to participants now.
Of its 262 completed or terminated interventional studies of FDA-regulated products, 196 (75%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Has any contraindications for completing a brain MRI scan.
a. The subject's head must fit within the head coil.
Participants will receive low-intensity focused ultrasound (LIFU) stimulation targeted to the centromedian nucleus of the thalamus (CMN), delivered by the head-worn ATTN201 device. Targeting is individualized for each participant's brain and skull anatomy using a spatial-mapping MRI acquired at baseline.
Device: ATTN201 Focused Ultrasound to the CMN
Participants will receive unfocused ultrasound from the same head-worn ATTN201 device on the same schedule. Unfocused ultrasound mimics the auditory and peripheral sensations of focused stimulation but does not generate substantive acoustic pressure at the CMN target relative to surrounding tissue.
Device: ATTN201 Unfocused Ultrasound
Low-intensity focused ultrasound delivered to the centromedian nucleus of the thalamus by the investigational ATTN201 head-worn device.
Also known as: ATTN201 Focused Ultrasound
Unfocused ultrasound delivered by the same device, serving as the control condition.
Incidence, Severity, and Relatedness of Adverse Events and Serious Adverse Events
Safety and tolerability of repeated ATTN201 stimulation, assessed by the incidence, severity, and relatedness of AEs and SAEs.
Time frame: From informed consent through the 3-month follow-up visit (up to ~5 months)
Incidence of New Clinically Significant Findings on Post-Treatment Safety MRI
Post-treatment brain MRI compared with the baseline MRI and reviewed for new clinically significant findings.
Time frame: From baseline through the post-treatment (~Week 5)
Study completion rate and adherence to scheduled study procedures
Proportion of randomized participants who complete all scheduled study procedures with acceptable adherence.
Time frame: From baseline through the post-treatment (~Week 5)
Change From Baseline in Clinical Dementia Rating - Sum of Boxes (CDR-SB)
CDR-SB scores range from 0 to 18, with higher scores indicating greater cognitive and functional impairment.
Time frame: Baseline, post-treatment (~Week 5), and 3-month follow-up (~Week 17)
Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog)
ADAS-Cog scores range from 0-85 with higher scores indicating greater cognitive impairment.
Time frame: Baseline, post-treatment (~Week 5), and 3-month follow-up (~Week 17)
Change From Baseline in the NULISASeq™ CNS Disease Panel 120
Blood samples will be collected using EDTA vials, minimally preprocessed, and stored for the duration of the study. Upon completion of the study, all samples will be analyzed using the NULISASeq™ CNS Disease Panel 120 for changes in Alzheimer's Disease biomarkers from baseline to post-treatment and follow-up.
Time frame: Baseline, post-treatment (~Week 5), and 3-month follow-up (~Week 17)
Change From Baseline in Alzheimer's Disease Cooperative Study Activities of Daily Living for MCI (ADCS-MCI-ADL)
Scores range from 0 to 53, with higher scores indicating better daily function.
Time frame: Baseline, post-treatment (~Week 5), and 3-month follow-up (~Week 17)
Change From Baseline in Slow-Wave Activity During Nap Opportunities
EEG-derived slow-wave activity (SWA) recorded during nap sessions.
Time frame: Baseline through the 2-week treatment period and post-treatment (~Week 5)
Change From Baseline in Objective Nocturnal Sleep: TST
Change from baseline in total sleep time derived from limited-channel home PSG.
Time frame: Baseline through the 2-week treatment period and post-treatment (~Week 5)
Change From Baseline in Objective Nocturnal Sleep: Rate of Delta Decline
Change from baseline in rate of delta decline derived from limited-channel home PSG.
Time frame: Baseline through the 2-week treatment period and post-treatment (~Week 5)
Change From Baseline in Objective Nocturnal Sleep: WASO
Change from baseline in sleep quality as measured by Wake After Sleep Onset derived from limited-channel home PSG.
Time frame: Baseline through the 2-week treatment period and post-treatment (~Week 5)
Change From Baseline in Objective Nocturnal Sleep: Percentage of Time Spent in Each Sleep Stage
Change from baseline in percentage of total sleep time spent in each sleep stage derived from limited-channel home PSG.
Time frame: Baseline through the 2-week treatment period and post-treatment (~Week 5)
Change From Baseline in Objective Nocturnal Sleep: SWA/SWS
Change from baseline in slow wave activity/slow-wave sleep derived from limited-channel home PSG.
Time frame: Baseline through the 2-week treatment period and post-treatment (~Week 5)
Change From Baseline in Objective Nocturnal Sleep: Onset Latency
Change from baseline in sleep onset latency derived from limited-channel home PSG.
Time frame: Baseline through the 2-week treatment period and post-treatment (~Week 5)
Change From Baseline in Subjective Sleep Quality and Daytime Alertness
Self-reported sleep quality and daytime alertness measured by visual analog scales (range 1-100).
Time frame: Baseline through the 2-week treatment period and post-treatment (~Week 5)
Incidence and Severity of Adverse Events Associated With the Unfocused Control Procedure
Safety and tolerability of the unfocused control condition, assessed by adverse event reporting.
Time frame: From the first control session through the 3-month follow-up visit (up to approximately 4 months)
Change From Baseline in Functional Connectivity of the Centromedian Nucleus of the Thalamus
Resting-state fMRI-derived functional connectivity between the centromedian nucleus of the thalamus (CMN) and known brain networks.
Time frame: Baseline to post-treatment (~Week 5)
Change From Baseline in Self-Reported Memory Complaints and Neurodegeneration-Related Psychiatric Symptoms
Measured by visual analog scales (range 1-100); higher scores indicate greater symptom burden.
Time frame: Baseline, during the 2-week treatment period, post-treatment (~Week 5), and 3-month follow-up (~Week 17)
Change From Baseline in NULISAseq Inflammation Panel 250
Samples will be collected via EDTA vials, minimally preprocessed, and stored for the duration of the study. Upon study completetion, samples will be analyzed for changes from baseline to post-treatment and follow-up in inflammatory biomarkers using the NULISAseq Inflammation Panel 250.
Time frame: Baseline, post-treatment (~Week 5), and 3-month follow-up (~Week 17)
Plan to share: Yes — De-identified individual participant data that support the results will be shared, provided the investigator who proposes to use the data has approval from an Institutional Review Board (IRB), Independent Ethics Committee (IEC), or Research Ethics Board (REB), as applicable, and executes a data use/sharing agreement with UCSF and Attune Neurosciences. Shared data will include participant-level clinical, cognitive, sleep, EEG, actigraphy, and fluid biomarker data underlying published results, together with a data dictionary. Direct identifiers will be removed and dates offset prior to release. Access is controlled rather than open because this study enrolls a small, deeply phenotyped cohort in which the combination of demographic, longitudinal physiological, and biomarker variables carries a residual risk of re-identification that open deposition would not adequately mitigate.
Supporting information: Study protocol, Sap, Icf, Analytic code
No publications or documents are linked to this record.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
This study is not yet recruiting, as verified in Oct 2026. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
University of California, San Francisco