Clinical trial NCT05643196: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Schizophrenia
Schizophrenia Schizoaffective
Lead sponsor: NYU Langone Health
Sponsor class: OTHER
Collaborators: name: The New York Community Trust
name: Doris Duke Charitable Foundation
First posted: 2022-12-08
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Change in Globus Pallidus Interna (GPi) Functional Connectivity During PLIFUS Intervention Visit
timeFrame: Immediately pre-sonication and 10 minutes post-sonication at Intervention Visit 1 (Day 0) and Intervention Visit 2 (Day 7)
Secondary outcomes:
measure: Change in Auditory Hallucinations Rating Scale (AHRS) Score From Baseline
timeFrame: Baseline, Final Study Visit (Day 14-16)
measure: Change in Delusions Experience Sampling Assessment (DESA) Score From Baseline
timeFrame: Baseline, Final Study Visit (Day 14-16)
Other outcomes:
Locations:
city: Brooklyn
country: United States
facility: NYU Langone Brooklyn
state: New York
city: New York
country: United States
facility: NYU Langone Health
state: New York
Study officials:
affiliation: NYU Langone Health
name: Donald Goff, MD
role: PRINCIPAL_INVESTIGATOR
References: