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Focused Ultrasound Modulation of the Globus Pallidus Interna in Schizophrenia

Primary Purpose

Schizophrenia, Schizophrenia Schizoaffective

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
PLIFUS
Sham PLIFUS
MRI
Sponsored by
NYU Langone Health
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Schizophrenia

Eligibility Criteria

18 Years - 50 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: 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. Exclusion Criteria: 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. Cochlear implants. Skin disease at intended stimulation sites The consumption of more than four alcoholic units within 24 hours before participation or any recreational drugs within 48 hours before participation.

Sites / Locations

  • NYU Langone BrooklynRecruiting
  • NYU Langone HealthRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

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

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

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.
Change in Globus Pallidus interna (GPi) Functional Connectivity during Sham Intervention Visit
Change in GPi functional connectivity measured via functional MRI (fMRI) captured pre-sonication and 10 minutes post-sonication during the Sham intervention visit.

Secondary Outcome Measures

Change in Psychosis Severity Rating Scale (PSRS) Score from Baseline: Auditory Hallucinations Subscale
1-item assessment of auditory hallucinations. Patient ranks severity of hallucinations on Likert scale from 0-100.
Change in Psychosis Severity Rating Scale (PSRS) Score from Baseline: Delusions Subscale
1-item assessment of delusions. Patient ranks severity of delusions on Likert scale from 0-100.
Change in Brief Psychiatric Rating Scale (BPRS) from Baseline
24-item clinician rating of psychiatric symptoms. Items are ranked on a scale from 0-7. The total score is the sum of responses and ranges from 24 to 216; higher scores indicate worse outcomes.

Full Information

First Posted
November 21, 2022
Last Updated
May 1, 2023
Sponsor
NYU Langone Health
Collaborators
The New York Community Trust, Doris Duke Charitable Foundation
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1. Study Identification

Unique Protocol Identification Number
NCT05643196
Brief Title
Focused Ultrasound Modulation of the Globus Pallidus Interna in Schizophrenia
Official Title
A Sham-Controlled Pilot Trial of Focused Ultrasound Modulation of the Globus Pallidus Interna in Schizophrenia
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 6, 2023 (Actual)
Primary Completion Date
September 30, 2024 (Anticipated)
Study Completion Date
September 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
NYU Langone Health
Collaborators
The New York Community Trust, Doris Duke Charitable Foundation

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Device Product Not Approved or Cleared by U.S. FDA
Yes
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Schizophrenia, Schizophrenia Schizoaffective

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
12 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Pulsed Low-Intensity Focused Ultrasound (PLIFUS), then Sham
Arm Type
Experimental
Arm Description
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.
Arm Title
Sham, then Pulsed Low-Intensity Focused Ultrasound (PLIFUS)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Device
Intervention Name(s)
PLIFUS
Other Intervention Name(s)
Sonicator-1000
Intervention Description
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
Intervention Name(s)
Sham PLIFUS
Intervention Description
Sham PLIFUS treatment delivers noise and patient experience that is identical to PLIFUS with Sonicator-1000 system.
Intervention Type
Device
Intervention Name(s)
MRI
Other Intervention Name(s)
Siemens 3T Prisma
Intervention Description
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.
Primary Outcome Measure Information:
Title
Change in Globus Pallidus interna (GPi) Functional Connectivity during PLIFUS Intervention Visit
Description
Change in GPi functional connectivity measured via functional MRI (fMRI) captured pre-sonication and 10 minutes post-sonication during the PLIFUS intervention visit.
Time Frame
Immediately Pre-Sonication at PLIFUS Intervention Visit, 10-minutes Post-Sonication at PLIFUS Intervention Visit (Up to Day 8)
Title
Change in Globus Pallidus interna (GPi) Functional Connectivity during Sham Intervention Visit
Description
Change in GPi functional connectivity measured via functional MRI (fMRI) captured pre-sonication and 10 minutes post-sonication during the Sham intervention visit.
Time Frame
Immediately Pre-Sonication at Sham Intervention Visit, 10-minutes Post-Sonication at Sham Intervention Visit (Up to Day 8)
Secondary Outcome Measure Information:
Title
Change in Psychosis Severity Rating Scale (PSRS) Score from Baseline: Auditory Hallucinations Subscale
Description
1-item assessment of auditory hallucinations. Patient ranks severity of hallucinations on Likert scale from 0-100.
Time Frame
Baseline, Day 14
Title
Change in Psychosis Severity Rating Scale (PSRS) Score from Baseline: Delusions Subscale
Description
1-item assessment of delusions. Patient ranks severity of delusions on Likert scale from 0-100.
Time Frame
Baseline, Day 14
Title
Change in Brief Psychiatric Rating Scale (BPRS) from Baseline
Description
24-item clinician rating of psychiatric symptoms. Items are ranked on a scale from 0-7. The total score is the sum of responses and ranges from 24 to 216; higher scores indicate worse outcomes.
Time Frame
Baseline, Day 14

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: 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. Cochlear implants. Skin disease at intended stimulation sites The consumption of more than four alcoholic units within 24 hours before participation or any recreational drugs within 48 hours before participation.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Donald Goff
Phone
646-754-4843
Email
donald.goff@nyulangone.org
First Name & Middle Initial & Last Name or Official Title & Degree
Wei Qi
Phone
212-961-4492
Email
wei.qi@nyulangone.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Donald Goff, MD
Organizational Affiliation
NYU Langone Health
Official's Role
Principal Investigator
Facility Information:
Facility Name
NYU Langone Brooklyn
City
Brooklyn
State/Province
New York
ZIP/Postal Code
11220
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Donald Goff, MD
Facility Name
NYU Langone Health
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Donald Goff, MD

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
The de-identified participant data from the final research dataset used in the published manuscript will be shared upon reasonable request beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research provided the investigator who proposes to use the data executes a data use agreement with NYU Langone Health. Requests may be directed to: [donald.goff@nyulangone.org]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
IPD Sharing 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.
IPD Sharing 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.

Learn more about this trial

Focused Ultrasound Modulation of the Globus Pallidus Interna in Schizophrenia

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