Focused Ultrasound Therapy for Schizophrenia

No longer recruiting at 1 trial location

Overseen By Donald Goff, MD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: NYU Langone Health

Must be taking: Antipsychotics

Disqualifiers: Substance abuse, Mood disorder, Suicidal ideation, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: 2 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called Pulsed Low-Intensity Focused Ultrasound (PLIFUS) for individuals with schizophrenia who experience ongoing hallucinations or delusions. Participants will receive both real and sham treatments in random order to determine if PLIFUS can improve brain connectivity and reduce psychotic symptoms. This trial suits those diagnosed with schizophrenia or schizoaffective disorder who have experienced consistent hallucinations or delusions for at least four weeks. As a Phase 2 trial, this research measures how well PLIFUS works in an initial, smaller group, offering participants a chance to contribute to important advancements in treatment.

Will I have to stop taking my current medications?

If you are taking antipsychotic medication, you must keep the dose the same for at least 4 weeks before starting the trial. If you are not on antipsychotic medication, you should not start any until the study is over, which is about 2 weeks.

What prior data suggests that this technique is safe for individuals with schizophrenia?

Research has shown that Pulsed Low-Intensity Focused Ultrasound (PLIFUS) is generally safe for people. Studies have found that this method can alter brain activity without causing harm. It uses sound waves to target specific brain areas without surgery, reducing the risk of complications like infections or healing problems associated with other treatments.

For instance, research on similar ultrasound treatments has demonstrated safety when used on different brain areas, such as the hippocampus. This suggests that PLIFUS might also be safe for treating schizophrenia.

Studies using PLIFUS have not consistently reported serious side effects. However, like any treatment, some mild side effects might occur. Overall, existing evidence supports the safety of PLIFUS for use in humans, making it a promising option for clinical trials. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment for schizophrenia?

Unlike the standard schizophrenia treatments, which typically involve antipsychotic medications that target neurotransmitter imbalances, Pulsed Low-Intensity Focused Ultrasound (PLIFUS) offers a novel approach by using sound waves to potentially modulate brain activity. Researchers are excited about PLIFUS because it is non-invasive and aims to precisely target specific brain regions without the side effects commonly associated with medication. This innovative method could open up new possibilities for managing symptoms more effectively and with fewer side effects than traditional treatments.

What evidence suggests that PLIFUS might be an effective treatment for schizophrenia?

Research suggests that Pulsed Low-Intensity Focused Ultrasound (PLIFUS), which participants in this trial will receive, might help with schizophrenia by altering brain activity. Studies have shown that this type of ultrasound can modify brain function without surgery. In animal studies, it improved behaviors similar to those seen in schizophrenia. Other research using similar ultrasound treatments in people with schizophrenia has also shown potential benefits. Overall, these early findings offer hope that PLIFUS could help reduce symptoms like hallucinations and delusions in people with schizophrenia. ^{2 3 5 6 7}

Who Is on the Research Team?

Donald Goff, MD

Principal Investigator

NYU Langone Health

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

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

I am not pregnant, nursing, or planning to become pregnant and will use birth control during the study.

I have been diagnosed with schizophrenia or schizoaffective disorder.

Exclusion Criteria

You have been diagnosed with a mood disorder or other mental health condition, except for schizophrenia, schizoaffective disorder, or schizophreniform disorder.

History of violence assessed by the Buss-Perry Aggression Questionnaire 45 and defined by violent physical contact or threat with a weapon.

Pregnant or nursing or positive urine pregnancy test.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive one session of PLIFUS and one session of sham PLIFUS in random order, one week apart

2 weeks

2 visits (in-person)

Follow-up

Participants are monitored for changes in functional connectivity and psychotic symptoms

2 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• MRI
• PLIFUS
• Sham PLIFUS

Trial Overview 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.

How Is the Trial Designed?

Group I: Sham, then Pulsed Low-Intensity Focused Ultrasound (PLIFUS) Experimental Treatment 3 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 Sham Experimental Treatment 3 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.

Who Is Running the Clinical Trial?

NYU Langone Health

Lead Sponsor

Trials

1,431

Recruited

838,000+

Max G. Schlapp Mental Hygiene Fund (New York Community Trust)

Collaborator

Trials

1

Recruited

20+

Tech4Health

Collaborator

Trials

1

Recruited

20+

The New York Community Trust

Collaborator

Trials

7

Recruited

1,200+

Doris Duke Charitable Foundation

Collaborator

Trials

65

Recruited

264,000+

Published Research Related to This Trial

In a study involving 16 patients with schizophrenia, high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) over the left dorsolateral prefrontal cortex did not show significant effects on negative symptoms compared to sham treatment.

While there was a trend for improvement in some symptoms with sham rTMS, the study concluded that HF-rTMS is not effective for treating negative symptoms of schizophrenia, suggesting the need for exploring alternative rTMS methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The double-blind sham-controlled study of high-frequency rTMS (20 Hz) for negative symptoms in schizophrenia: negative results. Novák, T., Horácek, J., Mohr, P., et al.[2006]

Bimodal repetitive transcranial magnetic stimulation (rTMS) significantly reduced symptoms of schizophrenia in 10 patients who were unresponsive to medication, with improvements noted in all subscales of the Positive and Negative Syndrome Scale (PANSS) by Day 29.

The treatment also showed potential benefits for short-term auditory verbal memory, as indicated by significant increases in neurocognitive test scores after the rTMS sessions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjunctive treatment of bimodal repetitive transcranial magnetic stimulation (rTMS) in pharmacologically non-responsive patients with schizophrenia: a preliminary study. Oh, SY., Kim, YK.[2011]

A randomized-controlled trial involving 144 patients with schizophrenia will test the efficacy of high-frequency transcranial random noise stimulation (hf-tRNS) to alleviate persistent symptoms, with the primary outcome being a 25% reduction in symptoms after 10 sessions.

The study aims to explore not only the clinical effects of hf-tRNS on symptoms like auditory hallucinations but also its impact on brain activity and cognitive functions, potentially establishing it as a new treatment option for patients resistant to traditional antipsychotics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Examining transcranial random noise stimulation as an add-on treatment for persistent symptoms in schizophrenia (STIM'Zo): a study protocol for a multicentre, double-blind, randomized sham-controlled clinical trial. Brunelin, J., Mondino, M., Haesebaert, J., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10754174/

Focused Ultrasound Stimulates the Prefrontal Cortex and ... Low-intensity pulsed ultrasound (LIPUS) improves behavioral deficits and ameliorates neuropathology in dizocilpine (MK-801)-treated rats. The ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05643196

Focused Ultrasound Modulation of the Globus Pallidus ... The primary objectives of this study are to examine the tolerability of pulsed low-intensity focused ultrasound (PLIFUS) and its effects on brain function ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11612502/

The therapeutic potential of low-intensity focused ultrasound ... LIFU is a promising modality for precise and invasive modulation of brain activity, capable of redefining the landscape of SUD treatment.

4. fusfoundation.org fusfoundation.org/diseases-and-conditions/schizophrenia/

Schizophrenia A clinical trial in Shanghai, China is using low intensity focused ultrasound to treat schizophrenia. The Foundation updates these pages ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT07099950

Dose-Dependent Effects of Low-Intensity Focused ... Low-intensity focused ultrasound (LIFU) has emerged as a tool to modulate the activity of deep brain structures noninvasively and reversibly, ...

6. reporter.nih.gov reporter.nih.gov/project-details/10209047

Low intensity focused ultrasound - NIH RePORTER Low intensity pulsed focused ultrasound (LIFU) applies non-invasive acoustic energy to safely modulate neural activity in translational models and non-human ...

7. frontiersin.org frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2022.825802/full

Low Intensity Focused Ultrasound for Non-invasive and ... A first-in-human repetitive, pulsed LIFU platform targeting the hippocampus has also recently been developed and shown to be safe (36).