Focused Ultrasound Modulation of the Globus Pallidus Interna in Schizophrenia

NCT ID: NCT05643196

Last Updated: 2025-05-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-04-06
• Study Completion Date: 2024-04-01

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.

Detailed Description

The primary objectives of this study are to examine the tolerability of pulsed low-intensity focused ultrasound (PLIFUS) and its effects on brain function measured via fMRI functional connectivity and symptom response in individuals with schizophrenia. A neuronavigated single-element piezoelectric device will be utilized to noninvasively deliver transcranial PLIFUS sonication to the right globus pallidus interna, a brain region implicated in schizophrenia. The goal of this pilot study is to establish feasibility and tolerability and to determine whether the sonication procedure produces effects on the imaging biomarker and on symptoms prior to proceeding to therapeutic trials using repeated administration.

Conditions

Schizophrenia; Schizophrenia Schizoaffective

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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

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.

Group Type: EXPERIMENTAL

PLIFUS

Intervention Type: 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.

Sham PLIFUS

Intervention Type: DEVICE

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

MRI

Intervention Type: 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.

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

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 Type: EXPERIMENTAL

PLIFUS

Intervention Type: 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.

Sham PLIFUS

Intervention Type: DEVICE

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

MRI

Intervention Type: 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.

Interventions

PLIFUS

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.

Intervention Type: DEVICE

Sham PLIFUS

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

Intervention Type: DEVICE

MRI

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.

Intervention Type: DEVICE

Other Intervention Names

Sonicator-1000; Siemens 3T Prisma

Eligibility Criteria

Inclusion Criteria

1. 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.

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

3. 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.

4. 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.

Exclusion Criteria

1. 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.

2. Diagnosis of major mood disorder or other Axis I disorder other than schizophrenia, schizoaffective disorder or schizophreniform disorder.

3. 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.

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

5. Pregnant or nursing or positive urine pregnancy test.

6. 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.

7. 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.

8. A history or brain surgery .

9. History of syncopal episode within the past 6 months.

10. A cardiac pacemaker or intra-cardiac lines.

11. An implanted neurostimulator.

12. Implanted medication infusion device.

13. Implanted metal devices or large ferromagnetic fragments in the head or upper body (excluding dental wire), or jewelry/piercing that cannot be removed.

14. Cochlear implants.

15. Skin disease at intended stimulation sites

16. The consumption of more than four alcoholic units within 24 hours before participation or any recreational drugs within 48 hours before participation.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The New York Community Trust

OTHER

Sponsor Role: collaborator

Doris Duke Charitable Foundation

OTHER

Sponsor Role: collaborator

NYU Langone Health

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Donald Goff, MD

Role: PRINCIPAL_INVESTIGATOR

NYU Langone Health

Locations

NYU Langone Brooklyn

Brooklyn, New York, United States

NYU Langone Health

New York, New York, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

22-00997

Identifier Type: -

Identifier Source: org_study_id