SONATA LIFU for OCD

This is a randomized, double-blind, sham-controlled study evaluating the safety and feasibility of ATTN201, an investigational, non-invasive, wearable ultrasound headband, in adults with obsessive-compulsive disorder (OCD). ATTN201 uses low-intensity focused ultrasound (LIFU), guided by magnetic resonance imaging (MRI), to deliver stimulation to the subthalamic nucleus (STN), a brain region implicated in OCD symptom circuits. This is the fifth study in which ATTN201 has been used in humans, and the device is not currently approved by the U.S. Food and Drug Administration (FDA) for clinical use outside of research.

Approximately 40 participants will be enrolled in this study, ages 18-80, will be enrolled at a single site in San Francisco. Participants will be randomly assigned in a 1:1 ratio to receive either active focused ultrasound stimulation (20 participants) or sham (inactive) stimulation (20 participants). Sham stimulation sounds the same as active stimulation but does not deliver a therapeutic ultrasound effect to the brain. Neither participants nor the study staff administering treatment will know which group a participant has been assigned to during the treatment period.

Participation lasts approximately 12 to 16 weeks and includes 14 in-person and remote visits.

Inclusion criteria

• Have a principal diagnosis of OCD according to the DSM-5 with duration of > 1 year
• Have a Y-BOCS of > 16
• Participants currently on OCD medication 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 psychiatrist through the duration of the study.
• Be between 22 to 80 years of age (inclusive) on the day of signing informed consent.
• Be able and willing to undergo a cranial MRI
• Be able and willing to wear an Attune device throughout the experimental sessions.
• Sign the informed consent form, in accordance with local requirements, after the scope and nature of the investigation have been explained to the subject, and before screening assessments.
• 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 determined by the investigator to be medically stable at baseline/randomization 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. Male participants should not father a child or donate sperm for this same period.
• Female participants who are sexually active agree to use two methods of contraception for the duration of the study or not be of childbearing potential as indicated by one of the following:

• Has reached natural menopause, defined as 45 years of age with ≥6 months of spontaneous amenorrhea
• Has had a hysterectomy;
• Has had bilateral tubal ligation; or
• Has had a bilateral oophorectomy (with or without a hysterectomy) and greater than 6 weeks have passed since the surgery

Exclusion criteria

• Has a current or prior history of bipolar I or II disorder, schizophrenia or other psychotic disorder, borderline personality disorder, Tourette's disorder
• Has acute suicidality or suicide attempt or self-injurious behavior in the last 6 months
• 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 (except for caffeine and nicotine)
• Has a history of traumatic brain injury with loss of consciousness, seizures,or other neurological disorders.
• Has any contraindications for completing a brain MRI scan.

a. The subject's head must fit within the head coil (32 or 64 channel), while wearing the MR-compatible device.

• Has had a ketamine or TMS treatment within the last month prior to recruitment.
• Has had any medical or psychiatric symptoms or conditions that could interfere with study activities or confound interpretation of study results.
• Has a recent or ongoing, uncontrolled, clinically significant medical condition where participation in the trial would pose a significant medical risk to the subject or would confound study results within 3 months of Screening, such as:

• Conditions including but not limited to diabetes, hypertension, Human Immunodeficiency Virus (HIV) or other relevant infections, thyroid or endocrine disease, Chronic Obstructive Pulmonary Disease (COPD), delirium, congestive heart failure, angina, cardiac or gastrointestinal disease, or renal disease requiring dialysis, or unstable malignancies.
• Major surgery including not limited to abdominal, thoracic, cardiac, or orthopedic surgery, or any procedure requiring general anesthesia.
• Subjects with recently controlled or treated medical conditions may be considered for re-screening on a case-by-case basis after consultation with the Sponsor.
• Has a history of hepatitis or liver disease that, in the opinion of the investigator, has been active within the 6 months prior to Visit 1.
• Is pregnant, is attempting to become pregnant, or is nursing children.
• Is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling, or child) who is an investigational site or sponsor staff directly involved with this trial.
• Has a Body Mass Index (BMI) >34 kg/m2. BMI is calculated by taking the subject's weight in kg and dividing by the subject's height in meters, squared