Does rTMS Induce Synaptic Plasticity?

November 27, 2024 updated by: Jong Yoon, Davidzon, Guido, M.D.

Does Repetitive Transcranial Magnetic Stimulation (rTMS) Induce Synaptic Plasticity?

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.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Palo Alto, California, United States, 94304
        • VA Palo Alto Health Care System
      • Stanford, California, United States, 94305
        • Stanford University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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
Device: PET-MR
Positron emission tomography and magnetic resonance imaging, with a scan duration of up to 120 minutes
Drug: [11C]UCB-J radiotracer
I.V. bolus administration of up to 15 mCi (equivalent to 0.3 rems) in the antecubital vein per injection
Other Names:
  • C11-UCB-J

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Synaptic Density Quantified by Regional Binding Potential (BP_ND)
Time Frame: Assessed during PET scans before and after rTMS therapy (90 minutes per scan)
Synaptic density change (Baseline minus Post Treatment) will be quantified between treatment responsive patients and treatment unresponsive patients 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 and the centrum semiovale as the reference region. This method has been recently utilized by other investigators in neuropsychiatric samples. 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.
Assessed during PET scans before and after rTMS therapy (90 minutes per scan)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Davidzon, Guido, M.D.

Collaborators

Stanford University

Investigators

  • Principal Investigator: Jong H Yoon, MD, Stanford University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 1, 2019

Primary Completion (Estimated)

February 1, 2025

Study Completion (Estimated)

February 1, 2025

Study Registration Dates

First Submitted

March 13, 2020

First Submitted That Met QC Criteria

March 13, 2020

First Posted (Actual)

March 17, 2020

Study Record Updates

Last Update Posted (Estimated)

December 2, 2024

Last Update Submitted That Met QC Criteria

November 27, 2024

Last Verified

November 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 54574

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

No current plan to share data

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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