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

ConditionsSchizoaffective Disorder Schizophreniform Disorder Schizophrenia

Trial statusNot yet recruiting

Trial phasePhase 1

Trial typeInterventional

Biological sexAll

Age18-55

SponsorNew York State Psychiatric Institute

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

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)

Trial design

Design model

Parallel

Treatments tested in this trial

Brexpiprazole
Drug
Brexpiprazole is an antipsychotic medication
Cariprazine
Drug
Cariprazine is an antipsychotic medication
[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.

Treatment groups

100 Participants

are divided into 8 treatment groups

Treatment groups

See each treatment group below.

Group A: Cariprazine 1mgExperimental treatment 2 interventions

Group B: Cariprazine 2mgExperimental treatment 2 interventions

Group C: Cariprazine 3mgExperimental treatment 2 interventions

Group D: Cariprazine 4mgExperimental treatment 2 interventions

Group E: Brexpiprazole 1mgExperimental treatment 2 interventions

Group F: Brexpiprazole 2mgExperimental treatment 2 interventions

Group G: Brexpiprazole 3mgExperimental treatment 2 interventions

Group H: Brexpiprazole 4mgExperimental treatment 2 interventions

Trial outcomes

Primary outcomes

Acute D2 and D3 Receptor Occupancy

Delta BPND in poscommissural putamen and midbrain

Time frame

Day 1

Upregulation of D3 receptor following subchronic administration of antipsychotics

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

Time frame

Day 15

Secondary outcomes

Positive and Negative Syndrome Scale (PANSS) Total Positive Symptoms

Correlations between changes in PANSS total positive symptoms and receptor binding will be examined.

Time frame

15 days

Positive and Negative Syndrome Scale (PANSS) Total Negative Symptoms

Correlations between changes in PANSS total negative symptom scores and receptor binding will be examined.

Time frame

15 days

MATRICS Cognitive Deficits (Composite Score)

Correlations between changes in cognitive deficits (MATRICS composite score) and receptor binding will be examined.

Time frame

15 days

Other outcomes

Abnormal Involuntary Movement Scale (AIMS) Score

Correlations between changes in extrapyramidal side effect scores (AIMS) and receptor binding will be examined.

Time frame

15 days

Simpson-Angus Scale (SAS) Score

Correlations between changes in extrapyramidal side effect scores (SAS) and receptor binding will be examined.

Time frame

15 days

Barnes Akathisia Rating Scale (BARS) Score

Correlations between changes in extrapyramidal side effect scores (BARS) and receptor binding will be examined.

Time frame

15 days

Locations

This trial has no locations.

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

New York State Psychiatric Institute

Lead sponsor

National Institute of Mental Health (NIMH)

Collaborator

Columbia University

Collaborator

Stony Brook Medicine

Collaborator

Source ClinicalTrials.gov

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