[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100659474":3},{"organization":4,"outcomesModule":7,"designInfo":75,"detailedDescription":87,"studyPopulation":78,"armGroups":88,"interventions":101,"overallOfficials":113,"centralContacts":117,"locations":123,"responsibleParty":141,"collaborators":143,"id":150,"slug":151,"hasResults":152,"nctId":153,"briefTitle":154,"officialTitle":155,"acronym":78,"eligibilityCriteria":156,"healthyVolunteers":152,"sex":157,"minAge":158,"maxAge":78,"enrollmentInfo":159,"targetDuration":78,"studyType":162,"phases":163,"briefSummary":165,"conditions":166,"keywords":170,"overallStatus":175,"whyStopped":78,"lastUpdateSubmitDate":176,"lastUpdatePostDateStruct":177,"startDateStruct":180,"completionDateStruct":182,"leadSponsor":184,"locationsCount":185},{"fullName":5,"class":6},"University of California, San Francisco","OTHER",{"primaryOutcomes":8,"secondaryOutcomes":20,"otherOutcomes":63},[9,13,17],{"measure":10,"description":11,"timeFrame":12},"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.","From informed consent through the 3-month follow-up visit (up to ~5 months)",{"measure":14,"description":15,"timeFrame":16},"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.","From baseline through the post-treatment (~Week 5)",{"measure":18,"description":19,"timeFrame":16},"Study completion rate and adherence to scheduled study procedures","Proportion of randomized participants who complete all scheduled study procedures with acceptable adherence.",[21,25,28,31,34,38,41,44,47,50,53,56,59],{"measure":22,"description":23,"timeFrame":24},"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.","Baseline, post-treatment (~Week 5), and 3-month follow-up (~Week 17)",{"measure":26,"description":27,"timeFrame":24},"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.",{"measure":29,"description":30,"timeFrame":24},"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.",{"measure":32,"description":33,"timeFrame":24},"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.",{"measure":35,"description":36,"timeFrame":37},"Change From Baseline in Slow-Wave Activity During Nap Opportunities","EEG-derived slow-wave activity (SWA) recorded during nap sessions.","Baseline through the 2-week treatment period and post-treatment (~Week 5)",{"measure":39,"description":40,"timeFrame":37},"Change From Baseline in Objective Nocturnal Sleep: TST","Change from baseline in total sleep time derived from limited-channel home PSG.",{"measure":42,"description":43,"timeFrame":37},"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.",{"measure":45,"description":46,"timeFrame":37},"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.",{"measure":48,"description":49,"timeFrame":37},"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.",{"measure":51,"description":52,"timeFrame":37},"Change From Baseline in Objective Nocturnal Sleep: SWA\u002FSWS","Change from baseline in slow wave activity\u002Fslow-wave sleep derived from limited-channel home PSG.",{"measure":54,"description":55,"timeFrame":37},"Change From Baseline in Objective Nocturnal Sleep: Onset Latency","Change from baseline in sleep onset latency derived from limited-channel home PSG.",{"measure":57,"description":58,"timeFrame":37},"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).",{"measure":60,"description":61,"timeFrame":62},"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.","From the first control session through the 3-month follow-up visit (up to approximately 4 months)",[64,68,72],{"measure":65,"description":66,"timeFrame":67},"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.","Baseline to post-treatment (~Week 5)",{"measure":69,"description":70,"timeFrame":71},"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.","Baseline, during the 2-week treatment period, post-treatment (~Week 5), and 3-month follow-up (~Week 17)",{"measure":73,"description":74,"timeFrame":24},"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.",{"allocation":76,"interventionModel":77,"interventionModelDescription":78,"primaryPurpose":79,"observationalModel":78,"timePerspective":78,"maskingInfo":80},"RANDOMIZED","PARALLEL",null,"TREATMENT",{"masking":81,"maskingDescription":78,"whoMasked":82},"QUADRUPLE",[83,84,85,86],"PARTICIPANT","CARE_PROVIDER","INVESTIGATOR","OUTCOMES_ASSESSOR","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).\n\nBackground 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.\n\nInvestigational 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.\n\nControl 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.\n\nStudy 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).",[89,95],{"label":90,"type":91,"description":92,"interventionNames":93},"Low-Intensity Focused Ultrasound to the CMN","EXPERIMENTAL","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.",[94],"Device: ATTN201 Focused Ultrasound to the CMN",{"label":96,"type":97,"description":98,"interventionNames":99},"Unfocused Ultrasound","SHAM_COMPARATOR","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.",[100],"Device: ATTN201 Unfocused Ultrasound",[102,109],{"type":103,"name":104,"description":105,"armGroupLabels":106,"otherNames":107},"DEVICE","ATTN201 Focused Ultrasound to the CMN","Low-intensity focused ultrasound delivered to the centromedian nucleus of the thalamus by the investigational ATTN201 head-worn device.",[90],[108],"ATTN201 Focused Ultrasound",{"type":103,"name":110,"description":111,"armGroupLabels":112,"otherNames":78},"ATTN201 Unfocused Ultrasound","Unfocused ultrasound delivered by the same device, serving as the control condition.",[96],[114],{"name":115,"affiliation":5,"role":116},"Andrew Krystal, MD","PRINCIPAL_INVESTIGATOR",[118],{"name":119,"role":120,"phone":121,"phoneExt":78,"email":122},"Andrew D Krystal, MD","CONTACT","415-514-0446","andrew.krystal@ucsf.edu",[124],{"facility":125,"status":78,"city":126,"state":127,"zip":128,"country":129,"countryCode":130,"cosmosGeoPoint":131,"geoPoint":136,"contacts":137},"University of California San Francisco","San Francisco","California","94107","United States","US",{"type":132,"coordinates":133},"Point",[134,135],-122.41942,37.77493,{"lat":135,"lon":134},[138,140],{"name":119,"role":120,"phone":139,"phoneExt":78,"email":122},"415-476-7702",{"name":119,"role":116,"phone":78,"phoneExt":78,"email":78},{"type":142,"investigatorFullName":78,"investigatorTitle":78,"investigatorAffiliation":78,"oldNameTitle":78,"oldOrganization":78},"SPONSOR",[144,147],{"name":145,"class":146},"Attune Neurosciences Inc","INDUSTRY",{"name":148,"class":149},"Gates Ventures","UNKNOWN","100659474","cmn-lifu-for-enhanced-glymphatic-clearance-in-amyloid-positive-mci-100659474",false,"NCT07866768","CMN LIFU for Enhanced Glymphatic Clearance in Amyloid-Positive MCI","Safety and Feasibility Study of ATTN201 Centromedian Nucleus of the Thalamus Focused Ultrasound Stimulation for Enhanced Glymphatic Clearance in Amyloid Positive Patients With Mild Cognitive Impairment","Inclusion Criteria:\n\n1. 65+ years old, male or female\n2. Amyloid positivity as assessed by either PET, CSF, or plasma.\n3. Qualify for an MCI Diagnosis.\n4. Study partner available for informant measures.\n5. Willing and able to undergo a brain MRI.\n6. If currently on AD or sleep medications, must be at the same stable dose(s) for at least 3 weeks prior to screening and throughout the course of the study, and must continue to be under the care of their treating neurologist through the duration of the study.\n7. Be able and willing to wear an Attune device during treatments\n8. Able to sign informed consent in accordance with local regulations.\n9. Be able to speak, read, and understand the language of the trial staff and the informed consent form.\n10. Possess the ability to respond verbally to questions, follow instructions, and complete study assessments.\n11. Be able to adhere to the stimulation protocol and visit schedules.\n12. Be medically stable at baseline\u002Frandomization as assessed by medical history and non-significant clinical results of safety labs and vital signs examination.\n\nExclusion Criteria:\n\n1. Early-onset Alzheimer's disease, as defined by a diagnosis occurring prior to age 65.\n2. Clinically significant depression, as defined by a score of \\>10 on the Geriatric Depression Scale\n3. Moderate to severe untreated obstructive sleep apnea, as defined by an Apnea-Hypopnea Index (AHI) ≥ 15.\n4. Has other medical or psychiatric symptoms or conditions that, in the opinion of the investigator, will interfere with study activities or confound interpretation of study results.\n5. Is on medication which, in the opinion of the investigator, will confound study results.\n6. Has a history of deep brain stimulation or ablative surgery\n7. Has a history of substance abuse including alcohol use disorder in the past 6 months\n8. Has a history of traumatic brain injury\n9. Has any contraindications for completing a brain MRI scan.\n\n   a. The subject's head must fit within the head coil.\n10. Has an uncontrolled medical condition which may impact study results.\n11. Is or has an immediate family member of staff directly involved with this trial.","ALL","65 Years",{"count":160,"type":161},28,"ESTIMATED","INTERVENTIONAL",[164],"NA","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.\n\nThe main questions it aims to answer are:\n\n1. What, if any, issues do participants have when using the ATTN201 device?\n2. Can participants complete the full study schedule?\n\nResearchers 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.\n\nParticipants will:\n\n* Visit the study site for memory and thinking tests, blood draws, a health check, and MRI scans of the brain\n* Record their sleep at home for at least 5 days with a sleep diary, a watch-like sensor, and a headband that measures brain waves\n* Be assigned by chance to focused or unfocused ultrasound\n* Take part in 10 nap sessions over 2 weeks while wearing the device, at the study site or at home\n* Return for a final visit to repeat the first tests, and may return for an optional visit 3 months later",[167,168,169],"Alzheimer's Disease (AD)","Mild Cognitive Impairment (MCI)","Mild Cognitive Impairment (MCI) Due to Alzheimer's Disease",[171,172,173,174],"Alzheimer's Disease","Sleep","Low-Intensity Focused Ultrasound","Mild Cognitive Impairment","NOT_YET_RECRUITING","2026-10-05",{"date":178,"type":179},"2026-10-08","ACTUAL",{"date":181,"type":161},"2026-09",{"date":183,"type":161},"2028-01",{"name":5,"class":6},1]