Does rTMS Induce Synaptic Plasticity?

NCT ID: NCT04311619

Last Updated: 2024-12-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Clinical Phase

PHASE1

Study Classification

INTERVENTIONAL

Study Start Date

2019-12-01

Study Completion Date

2025-02-01

Brief Summary

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The purpose of this study is to utilize the radioactive positron emission tomography (PET) tracer \[11C\]UCB-J to investigate the effect of repetitive transcranial magnetic stimulation (rTMS) on synaptic plasticity. UCB-J has been validated as a marker for synaptic density. We will use this tracer to examine if rTMS leads to changes in synaptic plasticity, specifically changes in synaptic density, in individuals receiving rTMS for MDD. If rTMS is proven effective for increasing synaptic plasticity, there is a significant potential of a new applicable treatment for a variety of diseases that affect brain physiology.

Detailed Description

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The objective of this project is to discover the neural mechanisms by which Major Depressive Disorder (MDD) is treated, so that we may gain insights into its pathophysiology, as well as to develop new biomarkers. We will utilize the PET tracer \[11C\]UCB-J, the first in human tracer of neural synapses, to test the hypothesis that the successful treatment of MDD with repetitive Transcranial Magnetic Stimulation (rTMS) is associated with increased synaptic density. We will use this tracer to measure synaptic density before and after rTMS treatment and compare change in synaptic density between subjects who respond to the rTMS treatment and those who do not respond to treatment.

The finding of a marked increase in synaptic density in participants who respond to rTMS treatment would point to the possibility of developing new treatments with the potential to modify disease through mitigating, preventing or remediating synaptic loss.

Conditions

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Major Depressive Disorder

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

OTHER

Blinding Strategy

NONE

Study Groups

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Major Depression Disorder Participants

Participants will undergo positron emission tomography-magnetic resonance (PET-MR) imaging using the \[11C\]UCB-J radiotracer before and after Repetitive Transcranial Magnetic Stimulation (rTMS) treatment

Group Type EXPERIMENTAL

[11C]UCB-J radiotracer

Intervention Type DRUG

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

PET-MR

Intervention Type DEVICE

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

Interventions

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[11C]UCB-J radiotracer

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

Intervention Type DRUG

PET-MR

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

Intervention Type DEVICE

Other Intervention Names

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C11-UCB-J

Eligibility Criteria

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Inclusion Criteria

* 18-70 years in age
* U.S. Veteran
* Diagnosis of MDD
* On a stable medication regimen for at least two weeks prior to testing
* Stable social environment and housing to enable regular attendance at clinic visits
* Ability to undergo cognitive testing, clinical assessments, and PET/MR scans
* Stable medical health
* Will undergo rTMS treatment for MDD at the VA Palo Alto
* 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
* Acute or unstable chronic medical illness that would affect participation or compliance with study procedures, e.g. unstable angina
* Unstable psychiatric symptoms that precludes consistent participation in the study, e.g. active current suicidal intent or plan, severe psychosis
* Inability to undergo PET/MR scan, e.g. claustrophobia, presence of ferromagnetic objects in subject's body
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Stanford University

OTHER

Sponsor Role collaborator

Davidzon, Guido, M.D.

OTHER

Sponsor Role lead

Responsible Party

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Jong Yoon

Associate Professor of Psychiatry and Behavioral Sciences

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Jong H Yoon, MD

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Locations

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VA Palo Alto Health Care System

Palo Alto, California, United States

Site Status

Stanford University

Stanford, California, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 28792356 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30014145 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12468889 (View on PubMed)

Chervyakov AV, Chernyavsky AY, Sinitsyn DO, Piradov MA. Possible Mechanisms Underlying the Therapeutic Effects of Transcranial Magnetic Stimulation. Front Hum Neurosci. 2015 Jun 16;9:303. doi: 10.3389/fnhum.2015.00303. eCollection 2015.

Reference Type BACKGROUND
PMID: 26136672 (View on PubMed)

Holmes SE, Scheinost D, Finnema SJ, Naganawa M, Davis MT, DellaGioia N, Nabulsi N, Matuskey D, Angarita GA, Pietrzak RH, Duman RS, Sanacora G, Krystal JH, Carson RE, Esterlis I. Lower synaptic density is associated with depression severity and network alterations. Nat Commun. 2019 Apr 4;10(1):1529. doi: 10.1038/s41467-019-09562-7.

Reference Type BACKGROUND
PMID: 30948709 (View on PubMed)

Other Identifiers

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54574

Identifier Type: -

Identifier Source: org_study_id