What is the mechanism of action of this treatment?

Common treatments for schizophrenia, such as rTMS and tDCS, work by modulating neural activity in targeted brain regions. rTMS uses magnetic fields to induce electrical currents in the brain, while tDCS applies a low electrical current to alter neuronal excitability. These methods aim to correct dysfunctional neural circuits associated with symptoms like hallucinations and delusions. For schizophrenia patients, these treatments offer a non-invasive alternative to pharmacotherapy, potentially reducing side effects and providing symptom relief when medications are ineffective. Techniques like PLIFUS, which target specific brain areas such as the right Globus Pallidus Internus, represent an emerging approach to precisely modulate neural activity and alleviate psychotic symptoms.

What side effects are associated with this type of intervention?

Common treatments for schizophrenia, such as antipsychotic medications, can cause side effects including weight gain, diabetes, dyslipidemia, extrapyramidal symptoms (e.g., tremors, rigidity), and tardive dyskinesia. Neuromodulation techniques like deep brain stimulation (DBS) and transcranial magnetic stimulation (TMS) can lead to side effects such as infection, hemorrhage, confusion, seizures, and hardware malfunctions. Specifically, DBS may also cause stimulation-related complications that are usually reversible by adjusting the stimulation parameters. While PLIFUS is still experimental, potential side effects could be similar to those of other neuromodulation techniques, though more research is needed to fully understand its safety profile.

What prior FDA approvals exist?

The FDA has approved several antipsychotic medications for the treatment of schizophrenia, including first-generation antipsychotics like haloperidol and chlorpromazine, and second-generation antipsychotics such as risperidone, olanzapine, quetiapine, and aripiprazole. These medications primarily target dopamine receptors to alleviate psychotic symptoms. In addition to pharmacotherapy, neuromodulation techniques like Transcranial Magnetic Stimulation (TMS) have been explored, although they are not yet widely approved for schizophrenia. The trial of Pulsed Low-Intensity Focused Ultrasound Stimulation (PLIFUS) targeting the right Globus Pallidus Internus represents an innovative approach, aiming to modulate neural activity and potentially alleviate psychotic symptoms.

What other types of research exist?

Promising alternatives to PLIFUS for schizophrenia treatment include Transcranial Magnetic Stimulation (TMS), which uses magnetic fields to stimulate nerve cells in the brain, and Deep Brain Stimulation (DBS), which involves implanting electrodes in specific brain areas to regulate abnormal impulses. Both methods have shown potential in modulating neural activity and alleviating symptoms in psychiatric conditions.

← Back to Search

Focused Ultrasound

Focused Ultrasound Therapy for Schizophrenia

Phase 2

Waitlist Available

Led By Donald Goff, MD

Research Sponsored by NYU Langone Health

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Must report current psychosis, as defined by a score of > 4 on one of the following psychosis items on the Brief Psychiatric Rating Scale (BPRS): suspiciousness, hallucinations, unusual thought content, or grandiosity continuously for at least 4 weeks.

Must have a diagnosis of either schizophrenia or schizoaffective disorder as established by a Structured Clinical Interview for DSM-V (SCID).

Must not have

History of syncopal episode within the past 6 months.

Significant medical or neurological illness by history or physical exam, including seizure disorder, history of loss of consciousness lasting more than 30 minutes related to head trauma or intellectual developmental disorder.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up immediately pre-sonication at sham intervention visit, 10-minutes post-sonication at sham intervention visit (up to day 8)

Awards & highlights

No Placebo-Only Group

Summary

This trial tests PLIFUS, a sound wave technique, on people with schizophrenia who have ongoing hallucinations or delusions. The goal is to see if targeting a specific brain area can improve their symptoms.

Who is the study for?

This trial is for individuals with schizophrenia or schizoaffective disorder who have been experiencing continuous mild or greater hallucinations or delusions for at least 4 weeks. Participants must be stable on their current antipsychotic medication dose, if any, for the past month, and females of childbearing potential must use reliable birth control. People with significant medical conditions, metal implants incompatible with MRI, substance abuse issues (excluding nicotine and THC), major mood disorders other than schizophrenia spectrum disorders, recent suicidal ideation or attempts are excluded.

What is being tested?

The study tests PLIFUS (Pulsed Low-Intensity Focused Ultrasound) targeting the right Globus Pallidus Interna in people with schizophrenia to see if it affects psychotic symptoms and brain function. Each participant will undergo one session of real PLIFUS and a sham (fake) treatment in random order a week apart. If early results show no benefit after four participants complete the sessions, the protocol may change to three sessions over five days.

What are the potential side effects?

Potential side effects from PLIFUS could include discomfort at the stimulation site on the head, headache during or after treatment, nausea, dizziness or lightheadedness. Since this is a pilot trial assessing efficacy and safety of PLIFUS in schizophrenia patients specifically focusing on psychotic symptoms related to auditory hallucinations and delusions.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

I have been experiencing severe symptoms of psychosis for at least 4 weeks.

Select...

I have been diagnosed with schizophrenia or schizoaffective disorder.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I have fainted in the last 6 months.

Select...

I do not have a major illness or condition affecting my brain.

Select...

I have had brain surgery in the past.

Select...

I do not have skin conditions at the intended treatment areas.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ immediately pre-sonication at sham intervention visit, 10-minutes post-sonication at sham intervention visit (up to day 8)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~immediately pre-sonication at sham intervention visit, 10-minutes post-sonication at sham intervention visit (up to day 8)

This trial's timeline: 3 weeks for screening, Varies for treatment, and immediately pre-sonication at sham intervention visit, 10-minutes post-sonication at sham intervention visit (up to day 8) for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Change in Globus Pallidus interna (GPi) Functional Connectivity during PLIFUS Intervention Visit

Change in Globus Pallidus interna (GPi) Functional Connectivity during Sham Intervention Visit

Secondary study objectives

Change in Brief Psychiatric Rating Scale (BPRS) from Baseline

Change in Psychosis Severity Rating Scale (PSRS) Score from Baseline: Auditory Hallucinations Subscale

Change in Psychosis Severity Rating Scale (PSRS) Score from Baseline: Delusions Subscale

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: Sham, then Pulsed Low-Intensity Focused Ultrasound (PLIFUS)Experimental Treatment3 Interventions

Participants will receive sham sonication on the first intervention visit, then PLIFUS sonication on the second intervention visit. Visits will be separated by 1 week. Sonication at both visits will be preceded and followed by fMRI and an exit medical examination. Sonication will be delivered in a pulse pattern over 10 minutes.

Group II: Pulsed Low-Intensity Focused Ultrasound (PLIFUS), then ShamExperimental Treatment3 Interventions

Participants will receive PLIFUS sonication on the first intervention visit, then sham sonication on the second intervention visit. Visits will be separated by 1 week. Sonication at both visits will be preceded and followed by fMRI and an exit medical examination. Sonication will be delivered in a pulse pattern over 10 minutes.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

PLIFUS

2023

Completed Phase 2

~20

Sham PLIFUS

2023

Completed Phase 2

~20

MRI

2009

Completed Phase 2

~2810

0 / 6Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for schizophrenia, such as rTMS and tDCS, work by modulating neural activity in targeted brain regions. rTMS uses magnetic fields to induce electrical currents in the brain, while tDCS applies a low electrical current to alter neuronal excitability. These methods aim to correct dysfunctional neural circuits associated with symptoms like hallucinations and delusions. For schizophrenia patients, these treatments offer a non-invasive alternative to pharmacotherapy, potentially reducing side effects and providing symptom relief when medications are ineffective. Techniques like PLIFUS, which target specific brain areas such as the right Globus Pallidus Internus, represent an emerging approach to precisely modulate neural activity and alleviate psychotic symptoms.

The Neural Crossroads of Psychiatric Illness: An Emerging Target for Brain Stimulation.Once- to twice-daily, 3-year domiciliary maintenance transcranial direct current stimulation for severe, disabling, clozapine-refractory continuous auditory hallucinations in schizophrenia.Short and long term effects of left and bilateral repetitive transcranial magnetic stimulation in schizophrenia patients with auditory verbal hallucinations: a randomized controlled trial.