[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"trial:NCT07710989":3,"trial-entities:NCT07710989":90,"trial-summary:NCT07710989":94},{"id":4,"nct_id":4,"org_study_id":5,"brief_title":6,"official_title":7,"overall_status":8,"completion_date":9,"status_verified_date":10,"last_update_date":11,"start_date":12,"sponsor_name":13,"lead_sponsor_class":14,"has_dmc":15,"brief_summary":16,"detailed_description":17,"conditions":18,"keywords":21,"study_type":27,"primary_purpose":28,"phases":29,"enrollment_info":31,"interventions":34,"primary_outcomes":44,"secondary_outcomes":52,"sex":56,"minimum_age":57,"maximum_age":58,"healthy_volunteers":59,"eligibility_criteria":60,"std_ages":64,"locations":66,"central_contacts":75,"overall_officials":81,"references":84,"see_also_links":89},"NCT07710989","24-42726","Mechanisms Evaluating Striatal Systems Imaging: LIFU Effects & Outcomes","Mechanisms of Low-intensity Focused Ultrasound Targeting Striatal Circuits Underlying Auditory Hallucinations in Schizophrenia","NOT_YET_RECRUITING","2027-12-01","2026-07","2026-07-27","2027-02-01","University of California, San Francisco","OTHER",null,"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.","Background:\n\nAuditory hallucinations affect approximately 70% of individuals with schizophrenia and often persist despite antipsychotic treatment, contributing substantially to disability and reduced quality of life. Neuroimaging studies have consistently demonstrated abnormal functional connectivity between the striatum and superior temporal cortex, implicating corticostriatal circuitry in the generation and maintenance of hallucinations. Among striatal regions, the caudate has been associated with aberrant self-monitoring, abnormal predictive processing, and hallucination severity, making it a promising therapeutic target. The current study builds on these findings by evaluating whether non-invasive neuromodulation of the caudate can normalize striatal-temporal network function and improve hallucination symptoms.\n\nStudy Objective:\n\nThis first-in-human, early Phase 1 investigator-initiated clinical trial will evaluate the safety, feasibility, tolerability, target engagement, and preliminary mechanistic effects of repeated-session low-intensity focused ultrasound (LIFU) targeting the caudate, a key striatal region implicated in auditory hallucinations in schizophrenia. The study will determine whether individualized LIFU can safely modulate deep corticostriatal circuits and reduce hallucination-related functional connectivity abnormalities while improving psychotic hallucination symptoms.\n\nStudy Design:\n\nParticipants with schizophrenia and persistent clinically significant auditory hallucinations will undergo MRI-guided, neuronavigated LIFU targeting an individualized caudate target, a key striatal region implicated in hallucination-related corticostriatal circuitry. The study incorporates repeated-session stimulation with sham control to evaluate safety, feasibility, neural target engagement, and preliminary efficacy. Resting-state functional MRI will be obtained before and after treatment to quantify changes in functional connectivity between the caudate and superior temporal cortex. Clinical outcomes will include validated measures of auditory hallucination severity, psychiatric symptoms, tolerability, and adverse events.\n\nScientific Rationale:\n\nLIFU provides a unique capability to non-invasively modulate deep brain structures with millimeter spatial precision that cannot be reached using conventional non-invasive brain stimulation approaches. By targeting the caudate, this study seeks to directly test the causal role of striatal circuitry in hallucination generation and determine whether modulation of corticostriatal connectivity produces measurable improvements in hallucination symptoms. The results will establish the safety and feasibility of this approach while providing mechanistic evidence to guide future randomized efficacy trials of circuit-based neuromodulation for schizophrenia.\n\nSafety and Feasibility of LIFU This study has been designated a non-significant risk (NSR) device study by the UCSF Institutional Review Board and follows International Transcranial Ultrasonic Stimulation Safety and Standards Consortium (ITRUSST) recommendations. Individualized MRI-guided targeting and subject-specific acoustic simulations will optimize focal targeting while maintaining acoustic exposure within established safety limits. Participants will undergo continuous monitoring during treatment, structured adverse-event assessments using Common Terminology Criteria for Adverse Events (CTCAE) criteria, repeated tolerability assessments, and psychiatric safety monitoring throughout the study. Preliminary studies demonstrated that caudate-targeted LIFU was well tolerated, with no device-related adverse events beyond mild transient auditory sensations, supporting the safety and feasibility of repeated-session caudate-targeted LIFU in schizophrenia.",[19,20],"Schizophrenia","Auditory Hallucinations",[22,23,24,25,26],"LIFU","schizophrenia","auditory hallucinations","striatum","caudate","INTERVENTIONAL","TREATMENT",[30],"NA",{"count":32,"type":33},12,"ESTIMATED",[35],{"type":36,"name":22,"description":37,"armGroupLabels":38,"otherNames":41},"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.",[39,40],"Active LIFU","Sham Sonication",[42,43],"Active LIFU targeting the caudate","Sham Unfocused Sonication",[45,48],{"measure":20,"description":46,"timeFrame":47},"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)",{"measure":49,"description":50,"timeFrame":51},"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)",[53],{"measure":54,"description":55,"timeFrame":47},"Clinical Positive and Negative Symptoms","We will compare positive and negative symptoms using the Positive and Negative Syndrome Scale (PANSS) after LIFU targeting the caudate with baseline and the sham unfocused sonication condition.","ALL","18 Years","64 Years",false,{"inclusion":61,"exclusion":62,"raw_text":63},[],[],"Inclusion Criteria:\n\n1. 18-64 years of age, inclusive of all gender identities\n2. Current DSM-5 diagnosis of schizophrenia\n3. Persistent clinically-significant auditory hallucinations\n4. No contraindications for MRI, confirmed via standard safety screening procedures\n5. No neurological disorder\n6. Clinically stable (outpatient past 12 weeks; same dose medications in 4 weeks)\n7. Females will be tested for pregnancy and pregnant women will be excluded.\n\nExclusion Criteria:\n\nClinically significant neurological disorder or MRI incompatibility",[65],"ADULT",[67],{"facility":13,"city":68,"state":69,"zip":70,"country":71,"geoPoint":72},"San Francisco","California","94158","United States",{"lat":73,"lon":74},37.77493,-122.41942,[76],{"name":77,"role":78,"phone":79,"email":80},"Karuna Subramaniam, PhD","CONTACT","415-476-6888","karuna.subramaniam@ucsf.edu",[82],{"name":77,"affiliation":80,"role":83},"PRINCIPAL_INVESTIGATOR",[85],{"pmid":86,"type":87,"citation":88},"41871683","BACKGROUND","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\u002Fj.brs.2026.103084. Epub 2026 Mar 21. No abstract available.",[],{"nct_id":4,"conditions":91,"biomarkers":93},[92,19],"Auditory Hallucination",[],{"nct_id":4,"found":95,"summary":96,"prompt_version":106},true,{"design":97,"status":98,"heading":99,"summary":100,"follow_up":101,"word_count":102,"commitments":103,"compensation":104,"drugs_mentioned":105},"This is a first-in-human, early Phase 1 interventional study with 12 participants. It compares active LIFU treatment to a sham procedure.","completed","LIFU for Auditory Hallucinations in Schizophrenia","This study is looking at a new way to help people with schizophrenia who hear voices (auditory hallucinations) even after taking their regular medicines. It's testing a device called low-intensity focused ultrasound (LIFU) that uses sound waves to target a specific part of the brain called the caudate. Researchers believe that problems with how the caudate communicates with other brain areas might cause hallucinations. This study will compare LIFU to a sham treatment (where the device is used but no actual sound waves are delivered) to see if LIFU is safe, can change brain activity, and might reduce hallucinations. You could join if you are 18-64 years old, have schizophrenia with persistent auditory hallucinations, and meet other health criteria. Success would mean LIFU is safe, changes brain connections, and improves hallucinations.","Your auditory hallucinations will be followed for 8 weeks after treatment. Brain connectivity will be assessed 5 days after treatment.",131,"You would receive either active LIFU or sham treatment. Your auditory hallucinations will be measured at the start and weekly for 8 weeks after treatment, and brain connectivity will be measured at the start and 5 days after treatment.","Not stated in the trial record.",[22],"v2"]