Focused Ultrasound Modulation of the Globus Pallidus Interna in Schizophrenia

NCT05643196 | Completed Phase 2 Results DMC FDA Device

• 1 other identifier: 22-00997
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 2

Brief Summary

This is a single-site, phase 2, sham-controlled random-order cross-over pilot trial of PLIFUS targeting the right GPi in individuals with schizophrenia. Twelve individuals with schizophrenia who report continuous hallucinations or delusions of mild or greater severity will receive one session of PLIFUS and one session of sham PLIFUS in random order, one week apart. If no effect of PLIFUS is detected on measures of functional connectivity or psychotic symptoms in the first four completers, the trial will be changed to 3 sessions of PLIFUS or sham administered over 5 days.

Conditions

Schizophrenia; Schizophrenia Schizoaffective

Outcome Measures

Primary Outcomes (1)

• Change in Globus Pallidus Interna (GPi) Functional Connectivity During PLIFUS Intervention Visit

  Change in GPi functional connectivity measured via functional MRI (fMRI) captured pre-sonication and 10 minutes post-sonication during the PLIFUS intervention visit.

  Immediately pre-sonication and 10 minutes post-sonication at Intervention Visit 1 (Day 0) and Intervention Visit 2 (Day 7)

Secondary Outcomes (2)

• Change in Auditory Hallucinations Rating Scale (AHRS) Score From Baseline

  Baseline, Final Study Visit (Day 14-16)

• Change in Delusions Experience Sampling Assessment (DESA) Score From Baseline

  Baseline, Final Study Visit (Day 14-16)

Study Arms (2)

Pulsed Low-Intensity Focused Ultrasound (PLIFUS), then Sham

EXPERIMENTAL

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.

Device: PLIFUS; Device: Sham PLIFUS; Device: MRI

Sham, then Pulsed Low-Intensity Focused Ultrasound (PLIFUS)

EXPERIMENTAL

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.

Device: PLIFUS; Device: Sham PLIFUS; Device: MRI

Interventions

PLIFUS DEVICE

The Sonicator-1000 system will non-invasively deliver ultrasound sonications transcranially that selectively target specific areas of the brain using a neuronavigation system and the participant's MRI brain scan. The sonication parameters follow FDA and Electrotechnical Technical Commission regulation standards for diagnostic and therapeutic ultrasound.

Also known as: Sonicator-1000

Pulsed Low-Intensity Focused Ultrasound (PLIFUS), then Sham; Sham, then Pulsed Low-Intensity Focused Ultrasound (PLIFUS)

Sham PLIFUS DEVICE

Sham PLIFUS treatment delivers noise and patient experience that is identical to PLIFUS with Sonicator-1000 system.

Pulsed Low-Intensity Focused Ultrasound (PLIFUS), then Sham; Sham, then Pulsed Low-Intensity Focused Ultrasound (PLIFUS)

MRI DEVICE

A total of 5 MRIs will be performed using a Siemens 3T Prisma; one prior to the intervention visit, and one preceding and one immediately after each of the two sonication/sham visits.

Also known as: Siemens 3T Prisma

Pulsed Low-Intensity Focused Ultrasound (PLIFUS), then Sham; Sham, then Pulsed Low-Intensity Focused Ultrasound (PLIFUS)

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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).
• If taking antipsychotic medication, the dose must be unchanged for at least 4 weeks prior to randomization. If not taking antipsychotic medication, must be intending not to start medication until after completion of the study (approximately 2 weeks)-this decision must be judged to be appropriate by the research psychiatrist and by the participant's clinician.
• If assigned female at birth and of childbearing potential, patients must
• have a negative urine pregnancy test (all participants assigned female at birth regardless of childbearing potential will be required to submit a pregnancy test), AND;
• not be nursing or planning a pregnancy for the duration of the study through 30 days after the last sonication visit, AND;
• be abstinent or willing to use a reliable method of birth control from the Screening Visit and continue with the same method until termination from the study.

You may not qualify if:

• Current substance abuse / dependence for substances other than nicotine and THC, (i.e. alcohol, amphetamines, barbiturates, etc.)
• A positive urine toxicology screen (excluding THC, tricyclic antidepressants, or benzodiazepines (if prescribed).
• Moderate or severe cannabis use disorder.
• Diagnosis of major mood disorder or other Axis I disorder other than schizophrenia, schizoaffective disorder or schizophreniform disorder.
• Current or recent suicidal ideation-- suicidal ideation with intent or plan (indicated by affirmative answers to items 4 or 5 of the Suicidal Ideation section of the baseline C-SSRS) in the 6 months prior to screening or subjects who represent a significant risk of suicide in the opinion of the investigator or a history of suicide attempt.
• 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.
• 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.
• Contraindication to MRI: Metal implants, pacemaker, or other metal in the body or piercings that cannot be removed, or claustrophobia. Individuals with tattoos will be excluded from imaging if tattoos cover more than 5% of the body surface, if a tattoo is greater than 20 cm, or if a tattoo is located on the face, neck or genitals. Individuals with a contraindication to MRI may participate in the trial but will be excluded from the elective MRI component.
• A history or brain surgery .
• History of syncopal episode within the past 6 months.
• A cardiac pacemaker or intra-cardiac lines.
• An implanted neurostimulator.
• Implanted medication infusion device.
• Implanted metal devices or large ferromagnetic fragments in the head or upper body (excluding dental wire), or jewelry/piercing that cannot be removed.

Sponsors & Collaborators

• NYU Langone Health: lead
• The New York Community Trust: collaborator
• Doris Duke Charitable Foundation: collaborator

Study Sites (2)

NYU Langone Brooklyn

Brooklyn, New York, 11220, United States

Location

NYU Langone Health

New York, New York, 10016, United States

Location

MeSH Terms

Conditions

Schizophrenia; Psychotic Disorders

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Results Point of Contact

• Title: Wei Qi
• Organization: NYU Langone Health

wei.qi@nyulangone.org

212-961-4492

Study Officials

• Donald Goff, MD

  NYU Langone Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 21, 2022
• First Posted: December 8, 2022
• Study Start: April 6, 2023
• Primary Completion: March 25, 2024
• Study Completion: April 1, 2024
• Last Updated: May 30, 2025
• Results First Posted: May 30, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research.
• Access Criteria: The investigator who proposed to use the data will be granted access upon reasonable request. Requests should be directed to donald.goff@nyulangone.org. To gain access, data requestors will need to sign a data access agreement.

Locations

US (2)