Longitudinal PET Imaging of Antipsychotic Binding to the Dopamine-3 Receptor in Schizophrenia

NCT07715253 | Not Yet Recruiting Phase 1 FDA Drug

• 2 other identifiers: NYSPI2026-311R01MH139651-01A1
• Study Type: interventional
• Target: 100
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a clinical trial in which 40 participants with schizophrenia will be randomized to 15 days of treatment with cariprazine (CAR) or brexpiprazole (BREX) in a single-blind manner. \[11C\]PHNO PET scans will be obtained before treatment and after 1 day and 15 days of treatment to examine the effects of antipsychotic medications on the dopamine-3 receptor (D3R). The overall objectives of the current study are to: 1) measure the acute binding of CAR/BREX to the D3R; 2) measure D3R availability for evidence of upregulation following subchronic administration of CAR/BREX in the same set of patients; 3) examine relationships between subchronic binding of CAR/BREX to, and upregulation of, the D3R vs. D2R and changes in positive symptoms, negative symptoms, and cognitive deficits. Relationships between subchronic binding of CAR/BREX and EPS will be explored.

Conditions

Schizoaffective Disorder; Schizophreniform Disorder; Schizophrenia

Keywords

schizophrenia

Outcome Measures

Primary Outcomes (2)

• Acute D2 and D3 Receptor Occupancy

  Delta BPND in poscommissural putamen and midbrain

  Day 1

• Upregulation of D3 receptor following subchronic administration of antipsychotics

  The availability of D3Rs following two weeks of antipsychotic treatment will be measured.

  Day 15

Secondary Outcomes (3)

• Positive and Negative Syndrome Scale (PANSS) Total Positive Symptoms

  15 days

• Positive and Negative Syndrome Scale (PANSS) Total Negative Symptoms

  15 days

• MATRICS Cognitive Deficits (Composite Score)

  15 days

Other Outcomes (3)

• Abnormal Involuntary Movement Scale (AIMS) Score

  15 days

• Simpson-Angus Scale (SAS) Score

  15 days

• Barnes Akathisia Rating Scale (BARS) Score

  15 days

Study Arms (8)

Cariprazine 1mg

EXPERIMENTAL

Cariprazine 1mg daily for 15 days

Drug: Cariprazine; Drug: [11C] PHNO

Cariprazine 2mg

EXPERIMENTAL

Cariprazine 2mg daily for 15 days

Drug: Cariprazine; Drug: [11C] PHNO

Cariprazine 3mg

EXPERIMENTAL

Cariprazine 3mg daily for 15 days

Drug: Cariprazine; Drug: [11C] PHNO

Cariprazine 4mg

EXPERIMENTAL

Cariprazine 4mg daily for 15 days

Drug: Cariprazine; Drug: [11C] PHNO

Brexpiprazole 1mg

EXPERIMENTAL

Brexpiprazole 1mg daily for 15 days

Drug: Brexpiprazole; Drug: [11C] PHNO

Brexpiprazole 2mg

EXPERIMENTAL

Brexpiprazole 2mg daily for 15 days

Drug: Brexpiprazole; Drug: [11C] PHNO

Brexpiprazole 3mg

EXPERIMENTAL

Brexpiprazole 3mg daily for 15 days

Drug: Brexpiprazole; Drug: [11C] PHNO

Brexpiprazole 4mg

EXPERIMENTAL

Brexpiprazole 4mg daily for 15 days

Drug: Brexpiprazole; Drug: [11C] PHNO

Interventions

Cariprazine DRUG

Cariprazine is an antipsychotic medication

Cariprazine 1mg; Cariprazine 2mg; Cariprazine 3mg; Cariprazine 4mg

[11C] PHNO DRUG

This is the radiotracer that will be used to examine antipsychotic binding to D2 and D3 receptors in this study. It is experimental and used for imaging purposes.

Brexpiprazole 1mg; Brexpiprazole 2mg; Brexpiprazole 3mg; Brexpiprazole 4mg; Cariprazine 1mg; Cariprazine 2mg; Cariprazine 3mg; Cariprazine 4mg

Brexpiprazole DRUG

Brexpiprazole is an antipsychotic medication

Brexpiprazole 1mg; Brexpiprazole 2mg; Brexpiprazole 3mg; Brexpiprazole 4mg

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Individuals, any gender or sex, aged 18 to 55, inclusive at screen
• Capable of understanding the study procedures and able to provide informed consent
• Diagnosed with schizophrenia, schizoaffective, or schizophreniform disorder
• Negative urine toxicology
• Antipsychotic free (by choice and for reasons unrelated to the study), and for at least 3 weeks (4 for aripiprazole or LAIs) at the time of the baseline PET scan, inclusive of any antipsychotic-free time prior to consent. \[Any patient who requires inpatient hospitalization or acute medication treatment for clinical stabilization during the medication free period will not be included in this study; any participant who in the clinical judgment of the PIs or any involved clinician is not stable or appropriate for a medication free period will not be included.\]
• PANSS total score \> 80 and \< 120 (inclusive)

You may not qualify if:

• Diagnosis of substance use disorder within the previous month
• A history of poor or inadequate response or hypersensitivity to CAR or BREX for any reason
• EKG abnormality that is clinically significant including a QTc interval \> 450 msec for men and \> 470 msec for women,
• Pregnant or breast-feeding women. Women of child-bearing potential must have a negative serum β-hCG pregnancy test at Visit 1, must have been using an acceptable method of contraception for 30 days before the study (i.e., before the first PET or MRI scan, whichever comes first), and must agree to do so for the whole study and 30 days after (unless post-menopausal or surgically sterile)
• Any clinically significant or unstable medical/neurological illness, condition, or disorder that is anticipated to potentially compromise participant safety on study medication
• Any material in the body that is a contraindication for MRI procedures or participated in prior nuclear medicine procedures in the past year that exceed FDA-defined limits when combined with radiation dosimetry from PET scanning in this protocol to avoid exceeding annual dosimetry limits (metal screener repeated before MRI scan). Individuals exposed to radiation in the workplace in the previous year will be excluded.
• Acute risk for suicide (i.e., score of 4-5 within the previous month or 6 within the previous 3 months on the CSSRS) or violence/homicide (e.g., homicidal ideation), or history of severe violent behavior or behavioral dyscontrol while antipsychotic-free
• A history of treatment resistance to antipsychotics or who have a duration of illness of greater than 20 years
• Claustrophobia
• Use of nicotine products within the previous month (prior to first PET scan)

Sponsors & Collaborators

• New York State Psychiatric Institute: lead
• National Institute of Mental Health (NIMH): collaborator
• Columbia University: collaborator
• Stony Brook Medicine: collaborator

MeSH Terms

Conditions

Psychotic Disorders; Schizophrenia

Interventions

brexpiprazole; cariprazine; naxagolide

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Central Study Contacts

Ragy Girgis, MD

CONTACT

646-774-5553; ragy.girgis@nyspi.columbia.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Non clinical personnel and PET data analysts
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Clinical Psychiatry

Study Record Dates

• First Submitted: July 11, 2026
• First Posted: July 20, 2026
• Study Start (Estimated): December 1, 2026
• Primary Completion (Estimated): August 30, 2030
• Study Completion (Estimated): November 30, 2030
• Last Updated: July 20, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share
• Time Frame: Data will be shared after the study has been completed, as per NIH guidelines.