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

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.

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Key information

Conditions

Schizophrenia Mental Disorders Schizophrenia Spectrum and Other Psychotic Disorders

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

VA Palo Alto Health Care System, Palo Alto, California, United States

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

[11C]UCB-J radiotracer

Drug

I.V. bolus administration of up to 15 mCi (equivalent to 0.3 rems) in the antecubital vein

PET-MR

Device

Positron emission tomography and magnetic resonance imaging, with a scan duration of up to 120 minutes

Primary outcomes

Cross-sectional differences in synaptic density between HC and SZ participants

Time frame: 120 minutes (scan duration)

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.

Study contacts

Contact information is provided by the study sponsor or research team.

Study Coordinator

CONTACT

[email protected]

650-849-0552

Sponsors and collaborators

Lead sponsor

Davidzon, Guido, M.D.

Other

Collaborators

Weston Havens Foundation

Registry information

Important dates

Study start: 2019
Primary completion: 2025
Study completion: 2025
First posted: Jul 31, 2019
Registry last updated: Dec 16, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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