Does rTMS Induce Synaptic Plasticity?

NCT04311619 | Withdrawn Phase 1 FDA Drug FDA Device

• 1 other identifier: 54574
• Study Type: interventional
• Target: N/A
• 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 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.

Conditions

Major Depressive Disorder

Outcome Measures

Primary Outcomes (1)

• Change in Synaptic Density Quantified by Regional Binding Potential (BP_ND)

  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)

Study Arms (1)

Major Depression Disorder Participants

EXPERIMENTAL

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

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 per injection

Also known as: C11-UCB-J

Major Depression Disorder Participants

PET-MR DEVICE

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

Major Depression Disorder Participants

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

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
• 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

Sponsors & Collaborators

• Davidzon, Guido, M.D.: lead
• Stanford University: collaborator

Study Sites (2)

VA Palo Alto Health Care System

Palo Alto, California, 94304, United States

Location

Stanford University

Stanford, California, 94305, United States

Location

Related Publications (5)

• 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

• 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.

  PMID: 26136672 BACKGROUND

• 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.

  PMID: 30948709 BACKGROUND

MeSH Terms

Conditions

Depressive Disorder, Major

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Study Officials

• Jong H Yoon, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: March 13, 2020
• First Posted: March 17, 2020
• Study Start: December 1, 2019
• Primary Completion: February 1, 2025
• Study Completion: February 1, 2025
• Last Updated: December 2, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)