Mechanisms Evaluating Striatal Systems Imaging: LIFU Effects & Outcomes

NCT07710989 | Not Yet Recruiting FDA Device

• 2 other identifiers: 24-427261685505
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

Individuals with schizophrenia often experience persistent auditory hallucinations despite treatment with antipsychotic medications. Research suggests that abnormal communication between the striatum and the auditory cortex contributes to hallucinations. This first-in-human, proof-of-concept Phase 1 study will evaluate the safety, feasibility, and preliminary effects of repeated-session low-intensity focused ultrasound (LIFU), a non-invasive neuromodulation technique targeting the striatum. The study will examine whether LIFU can safely modulate brain circuits involved in hallucinations, reduce abnormal communication between the striatum and auditory cortex, and improve auditory hallucination symptoms.

Conditions

Schizophrenia; Auditory Hallucinations

Keywords

LIFU; schizophrenia; auditory hallucinations; striatum; caudate

Outcome Measures

Primary Outcomes (2)

• Auditory Hallucinations

  We will compare hallucinations after LIFU to caudate with baseline and the sham unfocused sonication condition using the Visual Analog Scale (VAS) and Auditory Vocal Hallucination Rating Scales (AVHRS).

  Baseline and Post-Treatment (Weekly follow-up for 8 weeks)

• Caudate-superior temporal cortical (STC) connectivity

  We will compare functional connectivity using Fisher r-to-z values from the CONN toolbox between the caudate and STC after LIFU compared to baseline and the sham unfocused sonication condition

  Baseline and Post-Treatment ( Day 5)

Secondary Outcomes (1)

• Clinical Positive and Negative Symptoms

  Baseline and Post-Treatment (Weekly follow-up for 8 weeks)

Study Arms (2)

Active LIFU

ACTIVE COMPARATOR

Active LIFU targeting teh caudate

Device: LIFU

Sham Sonication

PLACEBO COMPARATOR

Sham Unfocused Sonication

Device: LIFU

Interventions

LIFU DEVICE

MRI-guided, neuronavigated low-intensity focused ultrasound (LIFU) delivered to the caudate target will be compared to sham unfocused sonication delivered using the same device and procedures as the active intervention but without focal ultrasound energy to the target.

Also known as: Active LIFU targeting the caudate, Sham Unfocused Sonication

Active LIFU; Sham Sonication

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• years of age, inclusive of all gender identities
• Current DSM-5 diagnosis of schizophrenia
• Persistent clinically-significant auditory hallucinations
• No contraindications for MRI, confirmed via standard safety screening procedures
• No neurological disorder
• Clinically stable (outpatient past 12 weeks; same dose medications in 4 weeks)
• Females will be tested for pregnancy and pregnant women will be excluded.

You may not qualify if:

• Clinically significant neurological disorder or MRI incompatibility

Sponsors & Collaborators

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

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94158, United States

Location

Related Publications (1)

• Subramaniam K, Attalla G, Mathew M, Alvarez JL, Dadgar-Kiani E, Mahadevan R, Nagarajan S, Murphy KR. Low-intensity focused ultrasound targeting striatal circuits in schizophrenia: feasibility, safety, and effects on hallucinations and striatal-temporal functional connectivity. Brain Stimul. 2026 May-Jun;19(3):103084. doi: 10.1016/j.brs.2026.103084. Epub 2026 Mar 21. No abstract available.

  PMID: 41871683 BACKGROUND

MeSH Terms

Conditions

Schizophrenia; Hallucinations

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Perceptual Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Karuna Subramaniam, PhD

  karuna.subramaniam@ucsf.edu

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Karuna Subramaniam, PhD

CONTACT

415-476-6888; karuna.subramaniam@ucsf.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 6, 2026
• First Posted: July 17, 2026
• Study Start (Estimated): February 1, 2027
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: July 27, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)