OCD LIFU Target Engagement

Pilot Study to Investigate Brain Targets for Neuromodulation in Obsessive-compulsive Disorder

The investigators will conduct a pilot study to evaluate the safety and feasibility of low-intensity focused ultrasound on obsessive-compulsive disorder (OCD) symptoms when delivered to subcortical brain targets. The investigators will use the ATTN201 device to deliver single sessions of unfocused and focused ultrasound to up to three brain targets over 4 study visits and assess the intervention through self-rated scales of OCD symptoms.

Study Overview

• Status: Recruiting
• Conditions: Obsessive Compulsive Disorder (OCD)
• Intervention / Treatment: Device: Low Intensity Focused Ultrasound

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Marshall Nambiar, MS; Phone Number: 215-746-8901; Email: marshall.nambiar@pennmedicine.upenn.edu

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • University of Pennsylvania
      • Principal Investigator: Katherine Scangos, MD, PhD
      • Contact: Marshall Nambiar, MS; Phone Number: 215-746-8901; Email: marshall.nambiar@pennmedicine.upenn.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Participants must be enrolled in the IRB #853085 study

The inclusion criteria for the IRB #853085 study, which are also included in this trial are:

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

1. Adults aged 18-60 years old
2. Chronic OCD (5 years preceding date of enrollment), diagnosed as per the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition guidelines (DSM-5)
3. Presence of obsessions, compulsions, or both time-consuming obsessions and compulsions that take more than one hour a day or cause significant distress or impairment in social, occupation, or other important areas of functioning Obsessive-compulsive symptoms that are not attributable to the physiological effects of a substance (e.g., a drug of abuse, a medication) or another medical condition
4. Disturbance not better explained by the symptoms of another mental disorder listed in the DSM-5 Severe OCD symptoms, as defined by Y-BOCS I score of 28 or higher, within two weeks prior to enrollment
5. Compulsions need to involve movement of the hands and/or arms so that the sleeve is able to detect participant's actions (cannot be solely mental or verbal compulsions)
6. Ability to understand procedure-related instructions and to complete study assessments in English, and ability to comply with protocol requirements (e.g., procedure visits, treatment schedule, follow-up visit schedule, evaluations, etc.), in the opinion of the Principal Investigator
7. Willingness and ability to provide written agreement to allow any and all forms of communication between the research team and treating clinician(s) 8 Willingness and ability to provide informed consent, in the opinion of the Principal Investigator

Exclusion Criteria:

An individual who meets any of the following criteria will be excluded from participation in this study:

1. Unable to undergo MRI scan

   • Presence of metallic implants or devices or tattoos
   • Claustrophobia or severe anxiety
   • Inability to remain still for duration of scan
2. Inability to fit and wear the ATTN201 device for the entire

Exclusion criteria for IRB study #853085 include:

1. Hearing loss that, in the opinion of the Principal Investigator, an audiologist, or a treating physician, is likely to affect the subject's ability to comply with all of the requirements of the study, or may affect the integrity of the study data
2. Pregnancy - this is an exclusion criterion because we will be intentionally increasing anxiety in participants to evaluate optimal strategies to provoke distress and then promote relaxation
3. Any past or present medical condition, disease, disorder, or injury that, in the opinion of the Principal Investigator, may reduce or hinder the subject's ability to fully comply with all study requirements for the duration of the study or may impact, compromise, or affect the integrity of the data or results of the study.
4. Have a previous injury or surgery which could affect the nerve distribution
5. Have nerve damage (neuropathy)
6. Have a diagnosed neuromuscular disorder
7. Have a pacemaker
8. Have a history of skin allergies, psoriasis eczema, dermatitis, or other skin inflammation conditions
9. Compulsions cannot be completely mental or verbal actions, such as repeating words, counting objects, or performing mental rituals, and cannot involve only facial muscles/actions such as blinking or staring

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: LIFU Target Engagement Group; Participants in this single experimental group will undergo a series of low-intensity focused ultrasound (LIFU) sessions to evaluate safety and target engagement. Each participant will receive active LIFU stimulation at up to three personalized corticostriatal brain targets. The study utilizes a within-subject, sham-controlled design where participants receive both active LIFU and sham (placebo) stimulation across different sessions to compare physiological and clinical responses.

Device: Low Intensity Focused Ultrasound; Low-intensity focused ultrasound (LIFU) will be administered using the Attune ATTN201 device. This intervention is characterized by a multifocal approach targeting three specific subcortical regions: the subthalamic nucleus (STN), the dorsal anterior cingulate cortex (dACC), and the ventral striatum (VS+). Unlike clinical treatment trials, this is a target-engagement pilot study where each participant receives single sessions of sonication at these specific coordinates to evaluate acute physiological and symptomatic changes. The intervention includes a within-subject sham-controlled component, where the device is positioned identically but no ultrasound energy is delivered.; Other Names: LIFU

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Symptom Intensity through VAS score	This outcome evaluates the change in symptom intensity using Visual Analog Scales (VAS) scores. VAS include questions regarding urges to compulse/resist compulsions and subjective units of distress (SUDs), measure the intensity of a patient's impulse to carry out or control and inhibit these compulsions, and the amount of distress they feel, and are on a scale between 0-100, where higher scores signify greater symptom severity.	From the first visit (Visit 1) through the final visit (Visit 10), approximately 6 weeks.
Changes in Imaging between Pre- and Post-Intervention	This outcome measure evaluates safety and efficacy through neuroimaging conducted prior to and following the intervention. These measures are intended to assess potential effects and target engagement associated with LIFU. Efficacy measures will include changes in MRI-derived metrics (e.g., functional connectivity and/or regional activation in predefined regions of interest associated with the stimulation target). Safety is assessed by the presence of new or worsening structural abnormalities, including edema, hemorrhage, or tissue injury.	Before the first visit (Visit 1) and after the final visit (Visit 10), approximately 6 weeks
Incidence of Adverse Events Assesed by Symptom Checklist	This outcome measure evaluates the incidence and severity of adverse events using a structured symptomatic checklist survey administered throughout the study period. The checklist captures the presence, frequency, and severity of potential adverse symptoms. Adverse events will be categorized by type, relatedness, and severity.	Immediately after each intervention session and up to 24 hours post-intervention, assessed across the intervention period (Visits 6-9).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Physiological Changes Measured by EMG	This outcome measure evaluates changes in muscle activity using surface electromyography (EMG) recorded from the forearm during sessions. EMG signals will be collected continuously and processed using standardized pipelines. Metrics will include various features (e.g., SNR (dB)) over defined time windows. Change in muscle activity will be assessed by comparing pre-sonication values to post-sonication values.	Baseline through end of intervention period (Visits 2-9), with EMG data collected at every in-person visit, approximately 4 weeks.
Change in Y-BOCS score after sonication	This outcome measures changes in Obsessive-Compulsive symptom severity using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), administered by a trained clinician. Scores range from 0-40, with higher scores representing greater symptom severity.	From the first baseline visit (Visit 1) through the final visit (Visit 10).
Change in Acceleration Measured by IMU	This outcome measure evaluates changes in forearm movement amplitude using inertial measurement unit (IMU)-derived acceleration data. Acceleration (m/s²) will be recorded continuously from a microcontroller-based IMU placed on the participant's forearm during in-person sessions and processed using standardized signal processing pipelines. Change in movement amplitude will be assessed by comparing pre-sonication and post-sonication values.	Baseline through end of intervention period (Visits 2-9), with IMU data collected at every in-person visit, approximately 4 weeks.
Change in Angular Velocity Measured by IMU	This outcome measure evaluates changes in forearm rotational movement using inertial measurement unit (IMU)-derived angular velocity data. Angular velocity (°/s) will be recorded continuously from a microcontroller-based IMU placed on the participant's forearm during in-person sessions and processed using standardized signal processing pipelines. Change in rotational movement will be assessed by comparing pre-sonication and post-sonication values.	Baseline through end of intervention period (Visits 2-9), with IMU data collected at every in-person visit, approximately 4 weeks.
Change in Heart Rate Assessed by Photoplethysmography (PPG)	This outcome evaluates changes in heart rate activity using photoplethysmography (PPG) recorded during sessions. PPG signals will be collected from sensors placed on the participant and processed using standardized pipelines. Changes in physiological response will be assessed by comparing pre to post-sonication values.	Baseline through end of intervention period (Visits 2-9), with PPG data collected at every in-person visit, approximately 6 weeks.

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Collaborators: Attune Neurosciences Inc
• Investigators: Principal Investigator: Katherine Scangos, MD, PhD, University of Pennsylvania

Study record dates

Study Major Dates

• Study Start (Actual): March 4, 2026
• Primary Completion (Estimated): May 19, 2026
• Study Completion (Estimated): May 19, 2026

Study Registration Dates

• First Submitted: March 25, 2026
• First Submitted That Met QC Criteria: April 22, 2026
• First Posted (Actual): April 30, 2026

Study Record Updates

• Last Update Posted (Actual): April 30, 2026
• Last Update Submitted That Met QC Criteria: April 22, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: OCD; LIFU
• Additional Relevant MeSH Terms: Mental Disorders; Anxiety Disorders; Obsessive-Compulsive Disorder
• Other Study ID Numbers: 25-0707

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data (IPD) will not be shared with outside researchers at this time to ensure the protection of participant privacy and to maintain strict compliance with the University of Pennsylvania Institutional Review Board (IRB) approved protocol.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes