NCT03737032

Brief Summary

For the proposed 2-year study, the investigators will conduct a within-subject, counterbalanced investigation using functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) to examine the acute effects of theta-burst stimulation (TBS) on function in dorsomedial prefrontal cortex (dmPFC) in 35 young adults with depression (18-25 years, 50% female).

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
29

participants targeted

Target at below P25 for not_applicable depression

Timeline
Completed

Started Jan 2020

Typical duration for not_applicable depression

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 29, 2018

Completed
11 days until next milestone

First Posted

Study publicly available on registry

November 9, 2018

Completed
1.2 years until next milestone

Study Start

First participant enrolled

January 31, 2020

Completed
2.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 31, 2022

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 31, 2022

Completed
1.6 years until next milestone

Results Posted

Study results publicly available

March 19, 2024

Completed
Last Updated

March 19, 2024

Status Verified

February 1, 2024

Enrollment Period

2.5 years

First QC Date

October 29, 2018

Results QC Date

July 27, 2023

Last Update Submit

February 23, 2024

Conditions

Depression

Outcome Measures

Primary Outcomes (1)

  • Dorsomedial Prefrontal Cortex Activation

    This measure captures brain function in the dorsomedial prefrontal cortex (dmPFC) based on blood oxygen level dependent (BOLD) response measured using functional magnetic resonance imaging (fMRI) during a reward task. Data are analyzed using Statistical Parametric Mapping. Magnitude of dmPFC response is in arbitrary units, with higher values reflecting higher activation. Theoretical minimum and maximum scores do not exist. Study hypotheses predict that dmPFC will decrease (based on statistical significance) with continuous TBS.

    Task fMRI is conducted after each of 3 TBS sessions (intermittent, continuous, sham; in randomized, counterbalanced order) at approx 3, 5, and 7 weeks after study entry.

Secondary Outcomes (2)

  • Positive Affect

    pre and post each of 3 TBS administrations, with TBS lasting up to 190 seconds. cTBS, iTBS, and sham TBS each occurred in a single day.

  • VS-dmPFC Functional Connectivity

    Task fMRI is conducted after each of 3 TBS sessions (intermittent, continuous, sham; in randomized, counterbalanced order). Sessions occur at approx 3, 5, and 7 weeks after study entry.

Study Arms (6)

Intermittent, Continuous, Sham Order

EXPERIMENTAL

3 sessions of theta burst stimulation administered in the following order: 1) Intermittent theta burst stimulation, 2) Continuous theta burst stimulation, 3) Sham theta burst stimulation.

Device: Intermittent Theta Burst StimulationDevice: Continuous Theta Burst StimulationDevice: Sham Theta Burst Stimulation

Intermittent, Sham, Continuous Order

EXPERIMENTAL

3 sessions of theta burst stimulation administered in the following order: 1) Intermittent theta burst stimulation, 2) Sham theta burst stimulation, 3) Continuous theta burst stimulation.

Device: Intermittent Theta Burst StimulationDevice: Continuous Theta Burst StimulationDevice: Sham Theta Burst Stimulation

Continuous, Intermittent, Sham Order

EXPERIMENTAL

3 sessions of theta burst stimulation administered in the following order: 1) Continuous theta burst stimulation, 2) Intermittent theta burst stimulation, 3) Sham theta burst stimulation.

Device: Intermittent Theta Burst StimulationDevice: Continuous Theta Burst StimulationDevice: Sham Theta Burst Stimulation

Continuous, Sham, Intermittent Order

EXPERIMENTAL

3 sessions of theta burst stimulation administered in the following order: 1) Continuous theta burst stimulation, 2) Sham theta burst stimulation, 3) Intermittent theta burst stimulation.

Device: Intermittent Theta Burst StimulationDevice: Continuous Theta Burst StimulationDevice: Sham Theta Burst Stimulation

Sham, Intermittent, Continuous Order

EXPERIMENTAL

3 sessions of theta burst stimulation administered in the following order: 1) Sham theta burst stimulation, 2) Intermittent theta burst stimulation, 3) Continuous theta burst stimulation.

Device: Intermittent Theta Burst StimulationDevice: Continuous Theta Burst StimulationDevice: Sham Theta Burst Stimulation

Sham, Continuous, Intermittent Order

EXPERIMENTAL

3 sessions of theta burst stimulation administered in the following order: 1) Sham theta burst stimulation, 2) Continuous theta burst stimulation, 3) Intermittent theta burst stimulation.

Device: Intermittent Theta Burst StimulationDevice: Continuous Theta Burst StimulationDevice: Sham Theta Burst Stimulation

Interventions

Intermittent Theta Burst StimulationDEVICE

Theta Burst Stimulation, a form of Transcranial Magnetic Stimulation, will be applied to the dorsomedial prefrontal cortex. will include 600 pulses delivered in brief bursts of three pulses with a frequency of 50 Hz, at an intensity of 110% of resting motor threshold, and administered every 200 ms (5 Hz). Bursts will be delivered without interruption for a total duration of 40 seconds.

Continuous, Intermittent, Sham OrderContinuous, Sham, Intermittent OrderIntermittent, Continuous, Sham OrderIntermittent, Sham, Continuous OrderSham, Continuous, Intermittent OrderSham, Intermittent, Continuous Order
Continuous Theta Burst StimulationDEVICE

Theta Burst Stimulation, a form of Transcranial Magnetic Stimulation, will be applied to the dorsomedial prefrontal cortex. will include 600 pulses delivered in brief bursts of three pulses with a frequency of 50 Hz, at an intensity of 110% of resting motor threshold, and administered every 200 ms (5 Hz). Bursts will be delivered during 2 second periods (10 bursts/period) interleaved with 8-second stimulation-free intervals, for a total duration of 190 seconds.

Continuous, Intermittent, Sham OrderContinuous, Sham, Intermittent OrderIntermittent, Continuous, Sham OrderIntermittent, Sham, Continuous OrderSham, Continuous, Intermittent OrderSham, Intermittent, Continuous Order
Sham Theta Burst StimulationDEVICE

For the sham of theta burst stimulation, the device providing Theta Burst Stimulation can be placed in the same position and turned on, creating a similar experience for the participant, without providing any neural stimulation. Sham TBS will be delivered with a Cool-B65 Active/Placebo Coil, which includes a sham setting, and MagLink research software.

Continuous, Intermittent, Sham OrderContinuous, Sham, Intermittent OrderIntermittent, Continuous, Sham OrderIntermittent, Sham, Continuous OrderSham, Continuous, Intermittent OrderSham, Intermittent, Continuous Order

Eligibility Criteria

Age18 Years - 25 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • DSM-5 Diagnosis of Major Depressive Disorder, Persistent Depressive Disorder (Dysthymia), Other Specified Depressive Disorder, or Other Unspecified Depressive Disorder

You may not qualify if:

  • Bipolar disorder, substance dependence, or lifetime history of psychosis
  • Neurological disorder (e.g., seizure disorder)
  • Pregnant
  • MRI contradictions: claustrophobia, permanent orthodontic devices, metal implants or other forms of metal in the body that cannot be removed

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

The University of Pittsburgh, Department of Psychiatry

Pittsburgh, Pennsylvania, 15213, United States

Location

Related Publications (22)

  • Forbes EE, Dahl RE. Neural systems of positive affect: relevance to understanding child and adolescent depression? Dev Psychopathol. 2005 Summer;17(3):827-50. doi: 10.1017/S095457940505039X.

    PMID: 16262994BACKGROUND

  • Damoiseaux JS, Rombouts SA, Barkhof F, Scheltens P, Stam CJ, Smith SM, Beckmann CF. Consistent resting-state networks across healthy subjects. Proc Natl Acad Sci U S A. 2006 Sep 12;103(37):13848-53. doi: 10.1073/pnas.0601417103. Epub 2006 Aug 31.

    PMID: 16945915BACKGROUND

  • Downar J, Daskalakis ZJ. New targets for rTMS in depression: a review of convergent evidence. Brain Stimul. 2013 May;6(3):231-40. doi: 10.1016/j.brs.2012.08.006. Epub 2012 Sep 7.

    PMID: 22975030BACKGROUND

  • Drysdale AT, Grosenick L, Downar J, Dunlop K, Mansouri F, Meng Y, Fetcho RN, Zebley B, Oathes DJ, Etkin A, Schatzberg AF, Sudheimer K, Keller J, Mayberg HS, Gunning FM, Alexopoulos GS, Fox MD, Pascual-Leone A, Voss HU, Casey BJ, Dubin MJ, Liston C. Resting-state connectivity biomarkers define neurophysiological subtypes of depression. Nat Med. 2017 Jan;23(1):28-38. doi: 10.1038/nm.4246. Epub 2016 Dec 5.

    PMID: 27918562BACKGROUND

  • Dunlop K, Gaprielian P, Blumberger D, Daskalakis ZJ, Kennedy SH, Giacobbe P, Downar J. MRI-guided dmPFC-rTMS as a Treatment for Treatment-resistant Major Depressive Disorder. J Vis Exp. 2015 Aug 11;(102):e53129. doi: 10.3791/53129.

    PMID: 26327307BACKGROUND

  • Etkin A, Egner T, Kalisch R. Emotional processing in anterior cingulate and medial prefrontal cortex. Trends Cogn Sci. 2011 Feb;15(2):85-93. doi: 10.1016/j.tics.2010.11.004. Epub 2010 Dec 16.

    PMID: 21167765BACKGROUND

  • Ferenczi EA, Zalocusky KA, Liston C, Grosenick L, Warden MR, Amatya D, Katovich K, Mehta H, Patenaude B, Ramakrishnan C, Kalanithi P, Etkin A, Knutson B, Glover GH, Deisseroth K. Prefrontal cortical regulation of brainwide circuit dynamics and reward-related behavior. Science. 2016 Jan 1;351(6268):aac9698. doi: 10.1126/science.aac9698.

    PMID: 26722001BACKGROUND

  • Forbes EE, Dahl RE. Research Review: altered reward function in adolescent depression: what, when and how? J Child Psychol Psychiatry. 2012 Jan;53(1):3-15. doi: 10.1111/j.1469-7610.2011.02477.x. Epub 2011 Nov 28.

    PMID: 22117893BACKGROUND

  • Forbes EE, Hariri AR, Martin SL, Silk JS, Moyles DL, Fisher PM, Brown SM, Ryan ND, Birmaher B, Axelson DA, Dahl RE. Altered striatal activation predicting real-world positive affect in adolescent major depressive disorder. Am J Psychiatry. 2009 Jan;166(1):64-73. doi: 10.1176/appi.ajp.2008.07081336. Epub 2008 Dec 1.

    PMID: 19047324BACKGROUND

  • Fox MD, Buckner RL, Liu H, Chakravarty MM, Lozano AM, Pascual-Leone A. Resting-state networks link invasive and noninvasive brain stimulation across diverse psychiatric and neurological diseases. Proc Natl Acad Sci U S A. 2014 Oct 14;111(41):E4367-75. doi: 10.1073/pnas.1405003111. Epub 2014 Sep 29.

    PMID: 25267639BACKGROUND

  • Grossheinrich N, Rau A, Pogarell O, Hennig-Fast K, Reinl M, Karch S, Dieler A, Leicht G, Mulert C, Sterr A, Padberg F. Theta burst stimulation of the prefrontal cortex: safety and impact on cognition, mood, and resting electroencephalogram. Biol Psychiatry. 2009 May 1;65(9):778-84. doi: 10.1016/j.biopsych.2008.10.029. Epub 2008 Dec 13.

    PMID: 19070834BACKGROUND

  • Haber SN, Knutson B. The reward circuit: linking primate anatomy and human imaging. Neuropsychopharmacology. 2010 Jan;35(1):4-26. doi: 10.1038/npp.2009.129.

    PMID: 19812543BACKGROUND

  • Hanlon CA, Dowdle LT, Austelle CW, DeVries W, Mithoefer O, Badran BW, George MS. What goes up, can come down: Novel brain stimulation paradigms may attenuate craving and craving-related neural circuitry in substance dependent individuals. Brain Res. 2015 Dec 2;1628(Pt A):199-209. doi: 10.1016/j.brainres.2015.02.053. Epub 2015 Mar 11.

    PMID: 25770818BACKGROUND

  • Huang YZ, Edwards MJ, Rounis E, Bhatia KP, Rothwell JC. Theta burst stimulation of the human motor cortex. Neuron. 2005 Jan 20;45(2):201-6. doi: 10.1016/j.neuron.2004.12.033.

    PMID: 15664172BACKGROUND

  • Opie GM, Vosnakis E, Ridding MC, Ziemann U, Semmler JG. Priming theta burst stimulation enhances motor cortex plasticity in young but not old adults. Brain Stimul. 2017 Mar-Apr;10(2):298-304. doi: 10.1016/j.brs.2017.01.003. Epub 2017 Jan 4.

    PMID: 28089653BACKGROUND

  • Rossi S, Hallett M, Rossini PM, Pascual-Leone A; Safety of TMS Consensus Group. Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research. Clin Neurophysiol. 2009 Dec;120(12):2008-2039. doi: 10.1016/j.clinph.2009.08.016. Epub 2009 Oct 14.

    PMID: 19833552BACKGROUND

  • Rossini PM, Burke D, Chen R, Cohen LG, Daskalakis Z, Di Iorio R, Di Lazzaro V, Ferreri F, Fitzgerald PB, George MS, Hallett M, Lefaucheur JP, Langguth B, Matsumoto H, Miniussi C, Nitsche MA, Pascual-Leone A, Paulus W, Rossi S, Rothwell JC, Siebner HR, Ugawa Y, Walsh V, Ziemann U. Non-invasive electrical and magnetic stimulation of the brain, spinal cord, roots and peripheral nerves: Basic principles and procedures for routine clinical and research application. An updated report from an I.F.C.N. Committee. Clin Neurophysiol. 2015 Jun;126(6):1071-1107. doi: 10.1016/j.clinph.2015.02.001. Epub 2015 Feb 10.

    PMID: 25797650BACKGROUND

  • Snaith RP, Hamilton M, Morley S, Humayan A, Hargreaves D, Trigwell P. A scale for the assessment of hedonic tone the Snaith-Hamilton Pleasure Scale. Br J Psychiatry. 1995 Jul;167(1):99-103. doi: 10.1192/bjp.167.1.99.

    PMID: 7551619BACKGROUND

  • Treadway MT, Buckholtz JW, Schwartzman AN, Lambert WE, Zald DH. Worth the 'EEfRT'? The effort expenditure for rewards task as an objective measure of motivation and anhedonia. PLoS One. 2009 Aug 12;4(8):e6598. doi: 10.1371/journal.pone.0006598.

    PMID: 19672310BACKGROUND

  • Watson D, Clark LA, Tellegen A. Development and validation of brief measures of positive and negative affect: the PANAS scales. J Pers Soc Psychol. 1988 Jun;54(6):1063-70. doi: 10.1037//0022-3514.54.6.1063.

    PMID: 3397865BACKGROUND

  • Zhang WN, Chang SH, Guo LY, Zhang KL, Wang J. The neural correlates of reward-related processing in major depressive disorder: a meta-analysis of functional magnetic resonance imaging studies. J Affect Disord. 2013 Nov;151(2):531-539. doi: 10.1016/j.jad.2013.06.039. Epub 2013 Jul 12.

    PMID: 23856280BACKGROUND

  • Gupta T, Karim HT, Jones NP, Ferrarelli F, Nance M, Taylor SF, Rogers D, Pogue AM, Seah THS, Phillips ML, Ryan ND, Forbes EE. Continuous theta burst stimulation to dorsomedial prefrontal cortex in young adults with depression: Changes in resting frontostriatal functional connectivity relevant to positive mood. Behav Res Ther. 2024 Mar;174:104493. doi: 10.1016/j.brat.2024.104493. Epub 2024 Feb 7.

    PMID: 38350221DERIVED

MeSH Terms

Conditions

Depression

Condition Hierarchy (Ancestors)

Behavioral SymptomsBehavior

Results Point of Contact

Title
Dr. Erika Forbes
Organization
University of Pittsburgh Medical Center, Department of Psychiatry
forbese@upmc.edu
412-383-5438

Study Officials

  • Erika E Forbes, Ph.D.

    The University of Pittsburgh

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
Yes
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, OUTCOMES ASSESSOR
Masking Details
The content of each TBS condition will be unknown to participants and to the research staff member conducting assessment of change neural, behavioral, and subjective response with TBS.
Purpose
BASIC SCIENCE
Intervention Model
CROSSOVER
Model Details: All participants will receive intermittent Theta Burst Stimulation (TBS), continuous TBS, and sham TBS mimicking stimulation, in randomized, double-blind order across three sessions.
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Professor of Psychiatry, Psychology, Pediatrics, & Clinical and Translational Science

Study Record Dates

First Submitted

October 29, 2018

First Posted

November 9, 2018

Study Start

January 31, 2020

Primary Completion

July 31, 2022

Study Completion

July 31, 2022

Last Updated

March 19, 2024

Results First Posted

March 19, 2024

Record last verified: 2024-02

Data Sharing

IPD Sharing
Will share

We will share all individual participant data (IPD) that underlie results in publications that report findings related to tests of our major hypotheses.

Shared Documents
STUDY PROTOCOL, SAP
Time Frame
Data will become available after results of planned tests are published or 5 years after completion of data collection, whichever occurs first. Data will remain available for 5 years.
Access Criteria
We will create procedures for other researchers to request data and will maintain quality assurance of data requests and data sharing. Researchers who share data will be affiliated and in good standing with academic institutions, will have current certification of training in responsible conduct of research, and will complete data requests describing the purpose of the project, the data requested, and the data analysis plan. Requests will be reviewed by the Principal Investigator and, if needed, other members of the research team. Criteria for sharing data will include characteristics described above, as well as scientific merit of the proposed use of data.

Locations

US(1)