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

NCT04038840 | Recruiting Phase 1 FDA Drug FDA Device

• 1 other identifier: 46106
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 2

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.

Conditions

Schizophrenia

Outcome Measures

Primary Outcomes (1)

• 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)

Study Arms (2)

Healthy Control (HC) Participants

EXPERIMENTAL

Participants will undergo positron emission tomography-magnetic resonance (PET-MR) imaging using the \[11C\]UCB-J radiotracer

Drug: [11C]UCB-J radiotracer; Device: PET-MR

Schizophrenia (SZ) Participants

EXPERIMENTAL

Participants will undergo positron emission tomography-magnetic resonance (PET-MR) imaging using the \[11C\]UCB-J radiotracer

Drug: [11C]UCB-J radiotracer; Device: PET-MR

Interventions

[11C]UCB-J radiotracer DRUG

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

Healthy Control (HC) Participants; Schizophrenia (SZ) Participants

PET-MR DEVICE

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

Healthy Control (HC) Participants; Schizophrenia (SZ) Participants

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Davidzon, Guido, M.D.: lead
• Weston Havens Foundation: collaborator

Study Sites (2)

VA Palo Alto Health Care System

Palo Alto, California, 94304, United States

RECRUITING

Stanford University

Stanford, California, 94305, United States

RECRUITING

Related Publications (8)

• Chong HY, Teoh SL, Wu DB, Kotirum S, Chiou CF, Chaiyakunapruk N. Global economic burden of schizophrenia: a systematic review. Neuropsychiatr Dis Treat. 2016 Feb 16;12:357-73. doi: 10.2147/NDT.S96649. eCollection 2016.

  PMID: 26937191 BACKGROUND

• Finnema SJ, Nabulsi NB, Eid T, Detyniecki K, Lin SF, Chen MK, Dhaher R, Matuskey D, Baum E, Holden D, Spencer DD, Mercier J, Hannestad J, Huang Y, Carson RE. Imaging synaptic density in the living human brain. Sci Transl Med. 2016 Jul 20;8(348):348ra96. doi: 10.1126/scitranslmed.aaf6667.

  PMID: 27440727 BACKGROUND

• Sekar A, Bialas AR, de Rivera H, Davis A, Hammond TR, Kamitaki N, Tooley K, Presumey J, Baum M, Van Doren V, Genovese G, Rose SA, Handsaker RE; Schizophrenia Working Group of the Psychiatric Genomics Consortium; Daly MJ, Carroll MC, Stevens B, McCarroll SA. Schizophrenia risk from complex variation of complement component 4. Nature. 2016 Feb 11;530(7589):177-83. doi: 10.1038/nature16549. Epub 2016 Jan 27.

  PMID: 26814963 BACKGROUND

• Nabulsi NB, Mercier J, Holden D, Carre S, Najafzadeh S, Vandergeten MC, Lin SF, Deo A, Price N, Wood M, Lara-Jaime T, Montel F, Laruelle M, Carson RE, Hannestad J, Huang Y. Synthesis and Preclinical Evaluation of 11C-UCB-J as a PET Tracer for Imaging the Synaptic Vesicle Glycoprotein 2A in the Brain. J Nucl Med. 2016 May;57(5):777-84. doi: 10.2967/jnumed.115.168179. Epub 2016 Feb 4.

  PMID: 26848175 BACKGROUND

• Feinberg I. Schizophrenia: caused by a fault in programmed synaptic elimination during adolescence? J Psychiatr Res. 1982-1983;17(4):319-34. doi: 10.1016/0022-3956(82)90038-3.

  PMID: 7187776 BACKGROUND

• Finnema SJ, Nabulsi NB, Mercier J, Lin SF, Chen MK, Matuskey D, Gallezot JD, Henry S, Hannestad J, Huang Y, Carson RE. Kinetic evaluation and test-retest reproducibility of [11C]UCB-J, a novel radioligand for positron emission tomography imaging of synaptic vesicle glycoprotein 2A in humans. J Cereb Blood Flow Metab. 2018 Nov;38(11):2041-2052. doi: 10.1177/0271678X17724947. Epub 2017 Aug 9.

  PMID: 28792356 BACKGROUND

• Chen MK, Mecca AP, Naganawa M, Finnema SJ, Toyonaga T, Lin SF, Najafzadeh S, Ropchan J, Lu Y, McDonald JW, Michalak HR, Nabulsi NB, Arnsten AFT, Huang Y, Carson RE, van Dyck CH. Assessing Synaptic Density in Alzheimer Disease With Synaptic Vesicle Glycoprotein 2A Positron Emission Tomographic Imaging. JAMA Neurol. 2018 Oct 1;75(10):1215-1224. doi: 10.1001/jamaneurol.2018.1836.

  PMID: 30014145 BACKGROUND

• Wu Y, Carson RE. Noise reduction in the simplified reference tissue model for neuroreceptor functional imaging. J Cereb Blood Flow Metab. 2002 Dec;22(12):1440-52. doi: 10.1097/01.WCB.0000033967.83623.34.

  PMID: 12468889 BACKGROUND

MeSH Terms

Conditions

Schizophrenia

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Study Officials

• Jong H Yoon, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Study Coordinator

CONTACT

650-849-0552; brain-research@stanford.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Psychiatry and Behavioral Sciences

Study Record Dates

• First Submitted: July 29, 2019
• First Posted: July 31, 2019
• Study Start: August 1, 2019
• Primary Completion: December 1, 2025
• Study Completion: December 1, 2025
• Last Updated: December 16, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)