Recruiting

Focused Ultrasound

Sponsor:

UCLA

Code:

NCT07866768

Conditions

Alzheimer's Disease (AD)

Mild Cognitive Impairment (MCI)

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

Eligibility Criteria

Sex: All

Age: 65+

Healthy Volunteers: Not accepted

Interventions

ATTN201 Focused Ultrasound to the CMN

ATTN201 Unfocused Ultrasound

Study Details

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:

1. What, if any, issues do participants have when using the ATTN201 device?
2. Can participants complete the full study schedule?

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:

  • 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

Study ID

NCT07866768

Start date

Oct, 2026

Status verified date

Oct, 2026

Completion date

Jan, 2028

Anticipated

Primary completion date

Jan, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 65+

Healthy Volunteers: Not accepted

Inclusion Criteria:

1. 65+ years old, male or female
2. Amyloid positivity as assessed by either PET, CSF, or plasma.
3. Qualify for an MCI Diagnosis.
4. Study partner available for informant measures.
5. Willing and able to undergo a brain MRI.
6. 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.
7. Be able and willing to wear an Attune device during treatments
8. Able to sign informed consent in accordance with local regulations.
9. Be able to speak, read, and understand the language of the trial staff and the informed consent form.
10. Possess the ability to respond verbally to questions, follow instructions, and complete study assessments.
11. Be able to adhere to the stimulation protocol and visit schedules.
12. Be medically stable at baseline/randomization as assessed by medical history and non-significant clinical results of safety labs and vital signs examination.

Exclusion Criteria:

1. Early-onset Alzheimer's disease, as defined by a diagnosis occurring prior to age 65.
2. Clinically significant depression, as defined by a score of >10 on the Geriatric Depression Scale
3. Moderate to severe untreated obstructive sleep apnea, as defined by an Apnea-Hypopnea Index (AHI) ≥ 15.
4. 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.
5. Is on medication which, in the opinion of the investigator, will confound study results.
6. Has a history of deep brain stimulation or ablative surgery
7. Has a history of substance abuse including alcohol use disorder in the past 6 months
8. Has a history of traumatic brain injury
9. Has any contraindications for completing a brain MRI scan.

a. The subject's head must fit within the head coil.
10. Has an uncontrolled medical condition which may impact study results.
11. Is or has an immediate family member of staff directly involved with this trial.

Study Design

Enrollment

28 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Low-Intensity Focused Ultrasound to the CMN

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.

sham comparator: Unfocused Ultrasound

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.

Interventions

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.

ATTN201 Unfocused Ultrasound

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

Primary outcome measure

  • Incidence, Severity, and Relatedness of Adverse Events and Serious Adverse Events [ 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 [ Time Frame: From baseline through the post-treatment (~Week 5) ]
  • Study completion rate and adherence to scheduled study procedures [ Time Frame: From baseline through the post-treatment (~Week 5) ]

Central Contacts and Locations

Central contacts

Andrew D Krystal, MD

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

Locations

University of California San Francisco

Recruiting

San Francisco, California, United States, 94107

Contacts

Andrew D Krystal, MD

415-476-7702andrew.krystal@ucsf.edu

Principal Investigator:

Andrew D Krystal, MD

More Information

Sponsor

University of California, San Francisco

Last update posted

Oct 14, 2026

Last verified

Oct, 2026

Keywords

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

Trial information was received from ClinicalTrials.gov and was last updated on 2026-10-15. This information was provided to ClinicalTrials.gov by University of California, San Francisco on 2026-10-14. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.