Treatment-resistant SchizophreniaNCT05259306
Low-Intensity Focused Ultrasound Neuromodulation of the Mediodorsal Thalamus for Treatment-Resistant Schizophrenia
A study testing Insightec Exablate Neuro MR-guided focused ultrasound transducer in people with Treatment-resistant Schizophrenia, run by NYU Langone Health at 1 site in United States.
Trial summary
This pilot study aims to investigate the use of MRI-guided low-intensity focused ultrasound (LIFU) to modulate neuronal activity within the thalamus in human subjects with treatment-resistant schizophrenia. Read more about this study
- Who is it for?
- Ages 21 to 80 years
- Conditions the study is for
- Treatment-resistant Schizophrenia
- What is being tested?
- Insightec Exablate Neuro MR-guided focused ultrasound transducer
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2027to Jun 2029
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subject has an age greater or equal to 21 years old.
- Subject has a diagnosis of schizophrenia as determined by a review of medical records, discussion with referring psychiatrist, as well as the Structured Clinical Interview for DSM-5 (SCID-5).
- Subject is determined to be treatment-resistant for at least one year prior to Visit 1 as demonstrated by clinical evidence (determined via medical records and referring psychiatrist) of persistent auditory hallucinations and/or delusions that have not responded to treatment with three adequate trials/regimens of antipsychotic medication, as follows:
- Adequate trials of any two different antipsychotic medications, belonging to different classes of at least 12 weeks equivalent to at least 500 mg/day of chlorpromazine within the previous five years.
- Subject has a score of at least moderate (4) on two of the three BPRS positive symptoms (conceptual disorganization, hallucinatory behavior, and unusual thought content) at all three Baseline Visits.
- Subject must be ambulatory.
- Female subjects must be practicing an acceptable method of contraception, postmenopausal, physically incapable of childbearing, or; if practicing an acceptable method of contraception, a negative urine pregnancy test must be confirmed at all three Baseline Visits
- Subject has decision-making capacity to provide informed consent, as determined by an independent psychiatrist.
Who cannot join
- Subject has a positive urine toxicology screen at any of the three Baseline Visits.
- Subject has medical contraindications to the procedure as determined by an internist or primary care physician.
- Subject is pregnant or breast-feeding.
- Subject has a history of alcohol or substance abuse within the past 6 months.
- Subject has a medical illness, comorbid psychiatric illness, and/or abnormal diagnostic finding that would interfere with the completion of the study, confound the results of the study, or pose risk to the patient.
- Subject has participated in another investigational drug trial or therapeutic trial within 30 days of Baseline Visit 1.
Show all 10Show fewer
- Subject has a neurologic condition or history of traumatic brain injury associated with loss of consciousness and/or intracranial bleeding.
- Subject is considered high suicide risk as screened by the Columbia-Suicide Severity Rating Scale (C-SSRS).
- Subject has a defibrillator, pacemaker, or other implants that would interfere with MRI
- Subject has significant social factors that greatly interfere with consistent follow up and/or support.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Low-Intensity Focused Ultrasound of the Mediodorsal Thalamus for Treatment-resistant Schizophrenia: Circuit Interrogation and Symptom Assessment
This pilot study aims to investigate the use of MRI-guided low-intensity focused ultrasound (LIFU) to modulate neuronal activity within the thalamus in human subjects with treatment-resistant schizophrenia.
Read the detailed description
Approximately 30% of patients with schizophrenia have symptoms that persist despite multiple antipsychotic medication trials including clozapine, and there is currently no evidence-based treatment option for this population. These patients often suffer psychological distress related to their psychotic symptoms, become chronically disabled, and are unable to lead meaningful lives. Several promising new treatment modalities are being explored including deep brain stimulation (DBS) in subjects with treatment-resistant schizophrenia. A pilot study at another institution is using DBS of the substantia nigra pars reticulata (SNr) to modulate circuitry in the thalamus by disinhibiting the mediodorsal (MD) nucleus of the thalamus. This approach follows evidence from multiple structural and functional studies implicating hypofunction of the MD thalamus in the pathophysiology of schizophrenia. This includes an association between MD hypofunction and both positive and cognitive symptoms of schizophrenia including auditory hallucinations and working memory, respectively. As DBS is an invasive neurosurgical procedure with small but definable risks of neurologic injury, a minimally invasive screening method to optimize patient selection for DBS would be optimal.
This pilot study aims to investigate the use of MRI-guided low-intensity focused ultrasound (LIFU) to modulate neuronal activity within the thalamus in human subjects with treatment-resistant schizophrenia. Focused ultrasound itself is a safe, incisionless technology with high spatial resolution and depth penetration that has been shown to stimulate and inhibit neuronal activity. At high intensities, focused ultrasound can be used to thermally ablate a specific region of brain tissue and has been FDA-approved for the treatment of essential tremor and tremor in Parkinson's disease via thermal ablation of the ventral intermediate (VIM) thalamus. In contrast, LIFU is non-ablative and thus can be used for transient neuromodulation with high spatial precision due to direct real-time MRI targeting. This pilot study aims to use non-ablative LIFU to target the MD thalamus noninvasively and specifically, with the aim of interrogating and modulating the neuronal circuitry involved in symptoms of schizophrenia.
- Conditions
- Treatment-resistant Schizophrenia
- Being tested
- Insightec Exablate Neuro MR-guided focused ultrasound transducer
- Medical subject headings
- Schizophrenia, Treatment-Resistant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Insightec Exablate Neuro MR-guided focused ultrasound transducerDevice
This study will be utilizing the Insightec Exablate Neuro MR-guided focused ultrasound transducer to deliver low-intensity ultrasonic energy precisely and safely to the target region of the brain. MRgFUS has been FDA approved at high-intensity to treat essential tremor and Parkinson's disease associated tremor. Device premarket approval number (PMA) is P150038, and FDA approval notice was July 11, 2016. This study will be using this device not to make any lesions in the brain (as it is currently FDA approved), but instead to use the precision and non-invasive nature of the device to target the MD thalamus region of the brain at intensities currently approved by the FDA for transcranial ultrasound.
| Study group | Role | What they receive |
|---|---|---|
| Treatment-resistant Schizophrenia group | Experimental | The subject will present for three baseline visits, followed by a treatment visit and subsequently follow-up visits at 24-hours, 48-hours, 1 week, 2 weeks, 1 month, and 3 months. Feasibility will be assessed as well as symptoms via detailed symptom rating scales at each visit. At the treatment visit itself, participants will undergo MR-guided low-intensity focused ultrasound of the MD thalamus. Receives: Device: Insightec Exablate Neuro MR-guided focused ultrasound transducer |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Patients who Complete All Visits Related to the Study
Measurement of feasibility of low-intensity focused ultrasound (LIFU) for treatment-resistant schizophrenia. Feasibility defined as two out of three patients completing all visits related to the study.
Measured: Up to Month 3
Secondary outcomes (3)
Change in Brief Psychiatric Rating Scale (BPRS) Score from Baseline
BPRS is a measurement of the severity of schizophrenia. It assesses the level of 18 symptom constructs including hostility, suspiciousness, hallucination, and grandiosity. The rater enters a number for each symptom construct that ranges from 1 (not present) to 7 (extremely severe), while items that are not assessed are scored as 0. The total score is the sum of responses and ranges from 18 to 126; higher scores indicate greater severity of symptoms.
Measured: Baseline, Month 3
Change in Positive and Negative Syndrome Scale (PANSS) Score from Baseline
PANSS is a 30-item medical scale used for measuring symptom severity of patients with schizophrenia. Items are rated on a 7-point scale (1=absent, 2=minimal, 3=mild, 4=moderate, 5=moderate severe, 6=severe, and 7=extreme). The total score is the sum of responses and ranges from 30 to 210; higher scores indicate greater illness severity.
Measured: Baseline, Month 3
Change in Montreal Cognitive Assessment (MoCA) Score from Baseline
MoCA is a rapid screening instrument for mild cognitive dysfunction. It assesses different cognitive domains: attention and concentration, executive functions, memory, language, visuoconstructional skills, conceptual thinking, calculations, and orientation. The total score is the sum of responses and ranges from 0 to 30; higher scores indicate less cognitive dysfunction. A normal score is defined as greater than or equal to 26.
Measured: Baseline, Month 3
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Feb 2022
- Study startJun 2027 (estimated)
- Primary completionJun 2028 (estimated)
- Study completionJun 2029 (estimated)
Why it stopped: Indefinite hold due to administrative issues.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Treatment-resistant SchizophreniaStudies of the same condition, open and under way.
- More trials run by NYU Langone HealthThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (estimated)
Sponsor and investigators
- Lead sponsor
- NYU Langone Health
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Alon Mogliner, MD, PhD, Principal investigator, NYU Langone Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05259306
- Sponsor's protocol ID
- 21-01291
- Status last verified
- Mar 2026
- First submitted
- 18 Jan 2022
- Last updated
- 2 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Yes: Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).
Study at a glance
From the registry record, last updated by the sponsor on 2 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Low-Intensity Focused Ultrasound of the Mediodorsal Thalamus for Treatment-resistant Schizophrenia: Circuit Interrogation and Symptom Assessment
- ClinicalTrials.gov ID
- NCT05259306
- Acronym / sponsor ID
- 21-01291
- Conditions
- Treatment-resistant Schizophrenia
- Study type
- Interventional
- Recruitment status
- SuspendedReason stopped: Indefinite hold due to administrative issues.
- Enrolment
- 3 participants (estimated)
- Lead sponsor
- NYU Langone HealthUniversity, hospital or other
- Study start
- Jun 2027 (estimated)
- Primary completion
- Jun 2028 (estimated)
- Study completion
- Jun 2029 (estimated)
- First posted
- 28 Feb 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This pilot study aims to investigate the use of MRI-guided low-intensity focused ultrasound (LIFU) to modulate neuronal activity within the thalamus in human subjects with treatment-resistant schizophrenia.
Detailed description
Approximately 30% of patients with schizophrenia have symptoms that persist despite multiple antipsychotic medication trials including clozapine, and there is currently no evidence-based treatment option for this population. These patients often suffer psychological distress related to their psychotic symptoms, become chronically disabled, and are unable to lead meaningful lives. Several promising new treatment modalities are being explored including deep brain stimulation (DBS) in subjects with treatment-resistant schizophrenia. A pilot study at another institution is using DBS of the substantia nigra pars reticulata (SNr) to modulate circuitry in the thalamus by disinhibiting the mediodorsal (MD) nucleus of the thalamus. This approach follows evidence from multiple structural and functional studies implicating hypofunction of the MD thalamus in the pathophysiology of schizophrenia. This includes an association between MD hypofunction and both positive and cognitive symptoms of schizophrenia including auditory hallucinations and working memory, respectively. As DBS is an invasive neurosurgical procedure with small but definable risks of neurologic injury, a minimally invasive screening method to optimize patient selection for DBS would be optimal.
This pilot study aims to investigate the use of MRI-guided low-intensity focused ultrasound (LIFU) to modulate neuronal activity within the thalamus in human subjects with treatment-resistant schizophrenia. Focused ultrasound itself is a safe, incisionless technology with high spatial resolution and depth penetration that has been shown to stimulate and inhibit neuronal activity. At high intensities, focused ultrasound can be used to thermally ablate a specific region of brain tissue and has been FDA-approved for the treatment of essential tremor and tremor in Parkinson's disease via thermal ablation of the ventral intermediate (VIM) thalamus. In contrast, LIFU is non-ablative and thus can be used for transient neuromodulation with high spatial precision due to direct real-time MRI targeting. This pilot study aims to use non-ablative LIFU to target the MD thalamus noninvasively and specifically, with the aim of interrogating and modulating the neuronal circuitry involved in symptoms of schizophrenia.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment-resistant Schizophrenia group | Experimental | Device: Insightec Exablate Neuro MR-guided focused ultrasound transducerThe subject will present for three baseline visits, followed by a treatment visit and subsequently follow-up visits at 24-hours, 48-hours, 1 week, 2 weeks, 1 month, and 3 months. Feasibility will be assessed as well as symptoms via detailed symptom rating scales at each visit. At the treatment visit itself, participants will undergo MR-guided low-intensity focused ultrasound of the MD thalamus. |
Who may qualify
- Ages
- 21 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Subject has an age greater or equal to 21 years old.
- Subject has a diagnosis of schizophrenia as determined by a review of medical records, discussion with referring psychiatrist, as well as the Structured Clinical Interview for DSM-5 (SCID-5).
- Subject is determined to be treatment-resistant for at least one year prior to Visit 1 as demonstrated by clinical evidence (determined via medical records and referring psychiatrist) of persistent auditory hallucinations and/or delusions that have not responded to treatment with three adequate trials/regimens of antipsychotic medication, as follows:
- Subject has a score of at least moderate (4) on two of the three BPRS positive symptoms (conceptual disorganization, hallucinatory behavior, and unusual thought content) at all three Baseline Visits.
- Subject must be ambulatory.
Key exclusion criteria (10 listed)
- Subject has a positive urine toxicology screen at any of the three Baseline Visits.
- Subject has medical contraindications to the procedure as determined by an internist or primary care physician.
- Subject is pregnant or breast-feeding.
- Subject has a history of alcohol or substance abuse within the past 6 months.
- Subject has a medical illness, comorbid psychiatric illness, and/or abnormal diagnostic finding that would interfere with the completion of the study, confound the results of the study, or pose risk to the patient.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Insightec Exablate Neuro MR-guided focused ultrasound transducerThis study will be utilizing the Insightec Exablate Neuro MR-guided focused ultrasound transducer to deliver low-intensity ultrasonic energy precisely and safely to the target region of the brain. MRgFUS has been FDA approved at high-intensity to treat essential tremor and Parkinson's disease associated tremor. Device premarket approval number (PMA) is P150038, and FDA approval notice was July 11, 2016. This study will be using this device not to make any lesions in the brain (as it is currently FDA approved), but instead to use the precision and non-invasive nature of the device to target the MD thalamus region of the brain at intensities currently approved by the FDA for transcranial ultrasound. | Device | Treatment-resistant Schizophrenia group |
Primary outcome
Number of Patients who Complete All Visits Related to the Study
Time frame: Up to Month 3
Measurement of feasibility of low-intensity focused ultrasound (LIFU) for treatment-resistant schizophrenia. Feasibility defined as two out of three patients completing all visits related to the study.
3 secondary outcomes
Change in Brief Psychiatric Rating Scale (BPRS) Score from Baseline
Time frame: Baseline, Month 3
Change in Positive and Negative Syndrome Scale (PANSS) Score from Baseline
Time frame: Baseline, Month 3
Change in Montreal Cognitive Assessment (MoCA) Score from Baseline
Time frame: Baseline, Month 3
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Apr 2026.
- Individual participant dataSharing planned: Yes. Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).
Related trials for Treatment-resistant Schizophrenia
Not yet recruiting
Deep Brain Stimulation for Treatment-Resistant Schizophrenia
Treatment Resistant Disorders
RecruitingPhase 3
Sequential Treatment Approaches for Treatment-Resistant Schizophrenia
Treatment-resistant Schizophrenia
Recruiting
Magnetic Seizure Therapy for Schizophrenia - Trial
Treatment Resistant Schizophrenia, Schizophrenia
Recruiting
Theta-Burst Transcranial Magnetic Stimulation for Treatment-Resistant Auditory Hallucinations
Auditory Verbal Hallucinations, Schizophrenia
Recruiting
French Minds Cohort: a French Longitudinal and Multimodal Cohort of Patients With Major Mood Disorders, Psychotic Disorders, Autism Spectrum Disorders, and Healthy Controls
Schizophrenia / Schizoaffective Disorder, First Episode Psychosis (FEP)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alon Mogliner, MD, PhD principal investigator
NYU Langone Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Insightec Exablate Neuro MR-guided focused ultrasound transducer in people with Treatment-resistant Schizophrenia, run by NYU Langone Health at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: paused, as of the sponsor's last update on 2 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Patients who Complete All Visits Related to the Study (time frame: Up to Month 3). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Apr 2026.