Focused Ultrasound for Behavioral Health

NCT07851038 | Not Yet Recruiting DMC FDA Device

• 1 other identifier: Pro00095585
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 1

Brief Summary

This is a double-blind, within-participant crossover, multi-site dose-finding study evaluating the safety, feasibility, and preliminary efficacy of repeated low-intensity focused ultrasound (LIFU) stimulation using the ATTN201 device across seven candidate deep-brain targets in adults with subsyndromal-to-moderate depression, anxiety, or obsessive-compulsive disorder. Every session delivers active ATTN201 stimulation; there is no sham or placebo condition. Participants and the on-site study staff who deliver stimulation and administer the clinical scales are blinded to the brain target and to the stimulation parameters assigned for each session by a constrained Bayesian optimization algorithm.

Conditions

Anxiety; Depression; Obsessive Compulsive Disorder (OCD)

Outcome Measures

Primary Outcomes (1)

• Patient-specific transdiagnostic score (TDx) at 1 week after stimulation

  TDx measured 1 week after each stimulation session. The TDx is a severity-weighted composite of normalized improvement on PHQ-9, GAD-7, and OCI-R; higher TDx indicates greater improvement.

  1 week after each stimulation session

Secondary Outcomes (22)

• Patient-specific transdiagnostic score (TDx) at 2 weeks after stimulation

  2 weeks after each stimulation session

• Posterior mean transdiagnostic score (TDx) at the best stimulation parameter set for each brain target

  At study completion, up to 19 months

• Change from pre-stimulation baseline in PHQ-9 total score

  Pre-stimulation baseline, 1 week after stimulation, and 2 weeks after stimulation

• Change from pre-stimulation baseline in GAD-7 total score

  Pre-stimulation baseline, 1 week after stimulation, and 2 weeks after stimulation

• Change from pre-stimulation baseline in OCI-R total score

  Pre-stimulation baseline, 1 week after stimulation, and 2 weeks after stimulation

Study Arms (7)

Basolateral amygdala (BLA)

EXPERIMENTAL

ATTN201 head-worn low-intensity focused ultrasound delivered to the basolateral amygdala (BLA). Sessions at which the constrained Bayesian optimization algorithm assigns this target; stimulation parameters (pulse repetition frequency, duty cycle, target pressure) vary within the ITRUSST-bounded search space. Participants may cross over to other target arms at subsequent sessions.

Device: ATTN201 head-worn focused ultrasound

Dorsal anterior cingulate cortex (dACC)

EXPERIMENTAL

ATTN201 head-worn low-intensity focused ultrasound delivered to the dorsal anterior cingulate cortex (dACC). Sessions at which the constrained Bayesian optimization algorithm assigns this target; stimulation parameters (pulse repetition frequency, duty cycle, target pressure) vary within the ITRUSST-bounded search space. Participants may cross over to other target arms at subsequent sessions.

Device: ATTN201 head-worn focused ultrasound

Anterior limb of internal capsule (ALIC)

EXPERIMENTAL

ATTN201 head-worn low-intensity focused ultrasound delivered to the anterior limb of the internal capsule (ALIC). Sessions at which the constrained Bayesian optimization algorithm assigns this target; stimulation parameters (pulse repetition frequency, duty cycle, target pressure) vary within the ITRUSST-bounded search space. Participants may cross over to other target arms at subsequent sessions.

Device: ATTN201 head-worn focused ultrasound

Centromedian nucleus of thalamus (CMN)

EXPERIMENTAL

ATTN201 head-worn low-intensity focused ultrasound delivered to the centromedian nucleus of the thalamus (CMN). Sessions at which the constrained Bayesian optimization algorithm assigns this target; stimulation parameters (pulse repetition frequency, duty cycle, target pressure) vary within the ITRUSST-bounded search space. Participants may cross over to other target arms at subsequent sessions.

Device: ATTN201 head-worn focused ultrasound

Rostral zona incerta (rZi)

EXPERIMENTAL

ATTN201 head-worn low-intensity focused ultrasound delivered to the rostral zona incerta (rZi). Sessions at which the constrained Bayesian optimization algorithm assigns this target; stimulation parameters (pulse repetition frequency, duty cycle, target pressure) vary within the ITRUSST-bounded search space. Participants may cross over to other target arms at subsequent sessions.

Device: ATTN201 head-worn focused ultrasound

Subthalamic nucleus (STN)

EXPERIMENTAL

ATTN201 head-worn low-intensity focused ultrasound delivered to the subthalamic nucleus (STN). Sessions at which the constrained Bayesian optimization algorithm assigns this target; stimulation parameters (pulse repetition frequency, duty cycle, target pressure) vary within the ITRUSST-bounded search space. Participants may cross over to other target arms at subsequent sessions.

Device: ATTN201 head-worn focused ultrasound

Anterior nucleus of thalamus (ANT)

EXPERIMENTAL

ATTN201 head-worn low-intensity focused ultrasound delivered to the anterior nucleus of the thalamus (ANT). Sessions at which the constrained Bayesian optimization algorithm assigns this target; stimulation parameters (pulse repetition frequency, duty cycle, target pressure) vary within the ITRUSST-bounded search space. Participants may cross over to other target arms at subsequent sessions.

Device: ATTN201 head-worn focused ultrasound

Interventions

ATTN201 head-worn focused ultrasound DEVICE

ATTN201 head-worn focused ultrasound

Anterior limb of internal capsule (ALIC); Anterior nucleus of thalamus (ANT); Basolateral amygdala (BLA); Centromedian nucleus of thalamus (CMN); Dorsal anterior cingulate cortex (dACC); Rostral zona incerta (rZi); Subthalamic nucleus (STN)

Eligibility Criteria

• Age: 22 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be between 22 and 80 years of age (inclusive) on the day of signing informed consent.
• Have at least one of the following at screening: PHQ-9 total score 5-16 (depression), GAD-7 total score 5-14 (anxiety), or OCI-R total score 14-27 (obsessive-compulsive disorder).
• If currently taking psychiatric medication, have been on the same stable dose(s) for at least 4 weeks prior to screening and be willing to maintain the regimen throughout the treatment period.
• Be able and willing to undergo a multi-sequence cranial MRI.
• Be willing to use the ATTN201 device during stimulation visits and to attempt use of monitoring devices (optional ambulatory EEG system, smart watch) during the pre- and post-stimulation monitoring blocks; use of the optional ambulatory EEG system does not affect eligibility.
• Sign the informed consent form, in accordance with local requirements, after the scope and nature of the investigation have been explained to the participant, and before any screening assessments.
• Be able to speak, read, and understand English.
• Be able to use a smartphone and the Attune platform.
• Possess the ability to respond verbally to questions, follow instructions, and complete study assessments.
• Be able to adhere to the treatment protocol and visit schedules through the 3-month post-treatment follow-up.
• Be judged by the investigator as likely to comply with study procedures and willing to participate in the entirety of the study.
• Be determined by the investigator to be medically stable at baseline as assessed by medical history and non-significant clinical results of a vital signs examination.
• Male participants must ensure a condom is used for all sexual intercourse and follow acceptable methods of contraception for their female partner for the entire duration of the study and for 90 days after the final study visit. Male participants should not father a child or donate sperm during this same period.
• Female participants who are sexually active agree to use two methods of contraception for the duration of the study and for 30 days after the final study visit, or not be of childbearing potential as indicated by natural menopause (≥12 consecutive months of spontaneous amenorrhea), hysterectomy, bilateral tubal ligation, bilateral oophorectomy (with or without hysterectomy) more than 6 weeks prior to screening, or a vasectomized partner with documented absence of sperm.

You may not qualify if:

• Columbia Suicide Severity Rating Scale (C-SSRS) score ≥ 3 (ideation with intent, with or without plan) at screening.
• Any suicide attempt within the past 12 months.
• Any change in psychiatric medication (start, stop, or dose change) within 4 weeks prior to screening.
• Has an unstable or severe medical or psychiatric condition that, in the investigator's judgment, would pose a safety risk to the participant or prevent completion of study procedures. Stable comorbid conditions (e.g., treated depression, anxiety, OCD, insomnia) within the protocol-specified score windows are permitted.
• Has an active, unstable substance use disorder including alcohol use disorder in the past 6 months (except for caffeine and nicotine). Participants on stable medication-assisted treatment (e.g., buprenorphine, methadone, naltrexone) for at least 6 months are eligible.
• Has a history of moderate-to-severe traumatic brain injury, or mild traumatic brain injury within the past 12 months.
• Has a history of seizure disorder or epilepsy, or any structural CNS lesion known to lower seizure threshold.
• Has any contraindications for completing a brain MRI scan (e.g., pacemaker, ferromagnetic implants).
• Body mass index (BMI) greater than 40 kg/m².
• Is pregnant, is attempting to become pregnant, or is nursing.
• Is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling, or child) who is an investigational site or Sponsor staff member directly involved with this trial.
• Has a known allergy or sensitivity to ultrasound gel, silicone, or adhesive materials used in monitoring devices.
• Has an active skin condition at sensor placement sites that would prevent device wear.
• Has received an investigational drug or device in another clinical study within 30 days before screening

Sponsors & Collaborators

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

Study Sites (1)

Attune Neurosciences, Inc.

San Francisco, California, 94107, United States

Location

MeSH Terms

Conditions

Depression; Anxiety Disorders; Obsessive-Compulsive Disorder

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior; Mental Disorders

Central Study Contacts

Keith Murphy, PhD

CONTACT

415-658-7001; keith@attuneneuro.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Masking Details: A single on-site research associate positions the device, runs the stimulation session, and administers the participant-facing assessments, and is blinded to the brain target and parameter combination in all of these functions. The stimulation condition is selected by the Bayesian optimization algorithm and pushed to the device as a sealed session; the operator screen does not display the target or the parameter values, and neither the research associate nor the participant is told them at any point during the study. Defocused delivery is one of the possible stimulation conditions and is not distinguishable from focused delivery by either party. The Lead Principal Investigator and the optimization team are unblinded as required to operate the adaptive design and do not deliver stimulation or administer participant-facing assessments. The independent Medical Monitor and the Data Safety and Monitoring Board receive unblinded safety data.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Within-participant crossover across candidate brain targets. Each participant receives between 3 and 10 ATTN201 stimulation sessions spaced approximately 7 days apart. For each session, a constrained Bayesian optimization algorithm assigns one candidate brain target and one set of stimulation parameters (pulse repetition frequency, duty cycle, pressure) from within the ITRUSST-bounded search space, informed by accumulated outcome data. Participants therefore cross over between target assignments over the course of their enrollment. Participants and on-site study staff are blinded to the assigned target and parameters. There is no sham or placebo condition; every session delivers active ATTN201 stimulation.

Study Record Dates

• First Submitted: August 28, 2026
• First Posted: October 1, 2026
• Study Start (Estimated): October 5, 2026
• Primary Completion (Estimated): April 5, 2028
• Study Completion (Estimated): May 17, 2028
• Last Updated: October 1, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Deposits occur on rolling quarterly delivery cycles beginning after enrollment of the first participant and continuing through study completion. Deposited data remain available thereafter under the retention terms of the ARPA-H designated data repository.
• Access Criteria: Access is governed by the data access procedures of the ARPA-H designated data repository. Requests for deposited data are made to the repository rather than to the sponsor.

Locations

US (1)