Imaging Synapses With [11C] UCB-J in the Human Brain

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to utilize the radioactive positron emission tomography (PET) tracer [11C]UCB-J to test the neural synaptic pruning hypothesis of schizophrenia. This imaging method allows for the quantification of synaptic density in the living human brain and has the unprecedented ability to directly examine the synaptic pathology underlying neuropsychiatric disease. The neural synaptic pruning hypothesis posits that a key pathogenic process of schizophrenia is the over-exuberant elimination of neural synapses during development. The confirmation of reduced synaptic density in schizophrenia as evidenced by [11C]UCB-J has the potential to lead to a number of ground-breaking clinical innovations, such as laboratory-based diagnostics and prognostics, and novel, disease-modifying treatments.

Official Title
-----------------
Imaging Synapses With [11C] UCB-J in the Human Brain

Conditions
-----------------
Schizophrenia

Intervention / Treatment
-----------------
* Drug: [11C]UCB-J radiotracer
* Device: PET-MR


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 18 - 65 years in age For SZ participants: On a stable medication regimen for at least two weeks prior to testing A clinical diagnosis of schizophrenia, schizophreniform, or schizoaffective disorder Able to complete a PET-MR scan without the use of sedation Exclusion Criteria: Active substance use within three months of testing IQ < 70 Major medical neurological illness or significant head trauma Pregnancy or breastfeeding Contraindication to MR scanning, including magnetic-resonance incompatible metal or hardware including pacemakers, cochlear implants, and bullets near a critical organ Weight > 350 lbs or a large body habitus that MR scanner cannot accommodate History of or current claustrophobia Inability to comply with basic study requirements such as following directions and punctuality For HC participants: Presence of a first degree relative with a psychotic disorder Lifetime diagnosis of major psychiatric illness For SZ participants: Unstable psychiatric symptoms at the time of testing, e.g. acute suicidality, prominent psychosis, or behavioral dyscontrol

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Healthy Control (HC) Participants<br>Participants will undergo positron emission tomography-magnetic resonance (PET-MR) imaging using the [11C]UCB-J radiotracer | Drug: [11C]UCB-J radiotracer<br>* I.V. bolus administration of up to 15 mCi (equivalent to 0.3 rems) in the antecubital vein<br>Device: PET-MR<br>* Positron emission tomography and magnetic resonance imaging, with a scan duration of up to 120 minutes<br>|
| Experimental: Schizophrenia (SZ) Participants<br>Participants will undergo positron emission tomography-magnetic resonance (PET-MR) imaging using the [11C]UCB-J radiotracer | Drug: [11C]UCB-J radiotracer<br>* I.V. bolus administration of up to 15 mCi (equivalent to 0.3 rems) in the antecubital vein<br>Device: PET-MR<br>* Positron emission tomography and magnetic resonance imaging, with a scan duration of up to 120 minutes<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cross-sectional differences in synaptic density between HC and SZ participants | Synaptic density will be quantified with the regional binding potential (BP_ND), a measure of [11C]UCB-J binding. BP_ND will be derived by using the simplified reference tissue model 2 (Wu & Carson, 2002) and the centrum semiovale as the reference region. This method has been recently utilized by other investigators in neuropsychiatric samples (Chen et al., 2018). Both exploratory voxel-wise BP_ND and region of interest (ROI) BP_ND will be compared across groups. ROIs include the striatum, dorsolateral prefrontal cortex, hippocampus, and superior temporal cortex. | 120 minutes (scan duration) |