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

Primary Purpose

Schizophrenia

Status

Unknown status

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

[11C]UCB-J radiotracer

PET-MR

About this trial

This is an interventional other trial for Schizophrenia

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

VA Palo Alto Health Care System
Stanford University

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Healthy Control (HC) Participants

Schizophrenia (SZ) Participants

Arm Description

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Full Information

NCT ID

NCT04038840

First Posted

July 29, 2019

Last Updated

November 4, 2020

Sponsor

Davidzon, Guido, M.D.

Collaborators

Weston Havens Foundation

1. Study Identification

Unique Protocol Identification Number

NCT04038840

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

November 2020

Overall Recruitment Status

Unknown status

Study Start Date

August 1, 2019 (Actual)

Primary Completion Date

September 2022 (Anticipated)

Study Completion Date

September 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Davidzon, Guido, M.D.

Collaborators

Weston Havens Foundation

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Schizophrenia

7. Study Design

Primary Purpose

Other

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Healthy Control (HC) Participants

Arm Type

Experimental

Arm Description

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

Arm Title

Schizophrenia (SZ) Participants

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

[11C]UCB-J radiotracer

Intervention Description

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

Intervention Type

Device

Intervention Name(s)

PET-MR

Intervention Description

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

Primary Outcome Measure Information:

Title

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

Description

Time Frame

120 minutes (scan duration)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jong H Yoon, MD

Organizational Affiliation

Stanford University

Official's Role

Principal Investigator

Facility Information:

Facility Name

VA Palo Alto Health Care System

City

Palo Alto

State/Province

California

ZIP/Postal Code

94304

Country

United States

Facility Name

Stanford University

City

Stanford

State/Province

California

ZIP/Postal Code

94305

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

IPD Sharing Plan Description

No current plan to share data

Citations:

PubMed Identifier

26937191

Citation

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.

Results Reference

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PubMed Identifier

27440727

Citation

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.

Results Reference

background

PubMed Identifier

26814963

Citation

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. Erratum In: Nature. 2022 Jan;601(7892):E4-E5.

Results Reference

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PubMed Identifier

26848175

Citation

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.

Results Reference

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PubMed Identifier

7187776

Citation

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.

Results Reference

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PubMed Identifier

28792356

Citation

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.

Results Reference

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PubMed Identifier

30014145

Citation

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.

Results Reference

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PubMed Identifier

12468889

Citation

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.

Results Reference

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

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