CMN LIFU for Enhanced Glymphatic Clearance in Amyloid-Positive MCI

NCT07866768 | Recruiting FDA Device

• 1 other identifier: 23-39270
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

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:

• Visit the study site for memory and thinking tests, blood draws, a health check, and MRI scans of the brain
• 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
• Be assigned by chance to focused or unfocused ultrasound
• Take part in 10 nap sessions over 2 weeks while wearing the device, at the study site or at home
• Return for a final visit to repeat the first tests, and may return for an optional visit 3 months later

Conditions

Alzheimer's Disease (AD); Mild Cognitive Impairment (MCI); Mild Cognitive Impairment (MCI) Due to Alzheimer's Disease

Keywords

Alzheimer's Disease; Sleep; Low-Intensity Focused Ultrasound; Mild Cognitive Impairment

Outcome Measures

Primary Outcomes (3)

• 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)

• 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)

• Study completion rate and adherence to scheduled study procedures

  Proportion of randomized participants who complete all scheduled study procedures with acceptable adherence.

  From baseline through the post-treatment (~Week 5)

Secondary Outcomes (13)

• Change From Baseline in Clinical Dementia Rating - Sum of Boxes (CDR-SB)

  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)

  Baseline, post-treatment (~Week 5), and 3-month follow-up (~Week 17)

• Change From Baseline in the NULISASeq™ CNS Disease Panel 120

  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)

  Baseline, post-treatment (~Week 5), and 3-month follow-up (~Week 17)

• Change From Baseline in Slow-Wave Activity During Nap Opportunities

  Baseline through the 2-week treatment period and post-treatment (~Week 5)

Other Outcomes (3)

• Change From Baseline in Functional Connectivity of the Centromedian Nucleus of the Thalamus

  Baseline to post-treatment (~Week 5)

• Change From Baseline in Self-Reported Memory Complaints and Neurodegeneration-Related Psychiatric Symptoms

  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

  Baseline, post-treatment (~Week 5), and 3-month follow-up (~Week 17)

Study Arms (2)

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.

Device: ATTN201 Focused Ultrasound to the CMN

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.

Device: ATTN201 Unfocused Ultrasound

Interventions

ATTN201 Focused Ultrasound to the CMN DEVICE

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

Low-Intensity Focused Ultrasound to the CMN

ATTN201 Unfocused Ultrasound DEVICE

Unfocused ultrasound delivered by the same device, serving as the control condition.

Unfocused Ultrasound

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• + years old, male or female
• Amyloid positivity as assessed by either PET, CSF, or plasma.
• Qualify for an MCI Diagnosis.
• Study partner available for informant measures.
• Willing and able to undergo a brain MRI.
• 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.
• Be able and willing to wear an Attune device during treatments
• Able to sign informed consent in accordance with local regulations.
• Be able to speak, read, and understand the language of the trial staff and the informed consent form.
• Possess the ability to respond verbally to questions, follow instructions, and complete study assessments.
• Be able to adhere to the stimulation protocol and visit schedules.
• Be medically stable at baseline/randomization as assessed by medical history and non-significant clinical results of safety labs and vital signs examination.

You may not qualify if:

• Early-onset Alzheimer's disease, as defined by a diagnosis occurring prior to age 65.
• Clinically significant depression, as defined by a score of \>10 on the Geriatric Depression Scale
• Moderate to severe untreated obstructive sleep apnea, as defined by an Apnea-Hypopnea Index (AHI) ≥ 15.
• 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.
• Is on medication which, in the opinion of the investigator, will confound study results.
• Has a history of deep brain stimulation or ablative surgery
• Has a history of substance abuse including alcohol use disorder in the past 6 months
• Has a history of traumatic brain injury
• Has any contraindications for completing a brain MRI scan.
• a. The subject's head must fit within the head coil.
• Has an uncontrolled medical condition which may impact study results.
• Is or has an immediate family member of staff directly involved with this trial.

Sponsors & Collaborators

• University of California, San Francisco: lead
• Attune Neurosciences Inc: collaborator
• Gates Ventures: collaborator

Study Sites (1)

University of California San Francisco

San Francisco, California, 94107, United States

RECRUITING

MeSH Terms

Conditions

Alzheimer Disease; Cognitive Dysfunction

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Cognition Disorders

Study Officials

• Andrew Krystal, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Andrew D Krystal, MD

CONTACT

415-514-0446; andrew.krystal@ucsf.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 20, 2026
• First Posted: October 8, 2026
• Study Start: October 1, 2026
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2028
• Last Updated: October 14, 2026

Record last verified: 2026-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, ANALYTIC CODE
• Time Frame: 9 to 60 months following publication of the primary results manuscript.
• Access Criteria: Requests should be directed to the Principal Investigator at andrew.krystal@ucsf.edu. Requesters must submit a written proposal stating the scientific question, the proposed analysis plan, and the variables required. Proposals will be reviewed by the study team and Attune Neurosciences, and a response provided within 60 days of receipt. The data use/sharing agreement will prohibit attempts at re-identification, prohibit onward transfer to third parties, restrict use to the approved analysis, and require acknowledgment of the source study and its funder.

Locations

US (1)