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Theta Burst Stimulation in Young Adults With Depression

Primary Purpose

Depression

Status

Completed

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

Intermittent Theta Burst Stimulation

Continuous Theta Burst Stimulation

Sham Theta Burst Stimulation

About this trial

This is an interventional basic science trial for Depression

Eligibility Criteria

18 Years - 25 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

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

Sites / Locations

The University of Pittsburgh, Department of Psychiatry

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Arm Label

Intermittent, Continuous, Sham Order

Intermittent, Sham, Continuous Order

Continuous, Intermittent, Sham Order

Continuous, Sham, Intermittent Order

Sham, Intermittent, Continuous Order

Sham, Continuous, Intermittent Order

Arm Description

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.

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.

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

fMRI-assessed brain function in the dorsomedial prefrontal cortex

Change in functional magnetic resonance imaging (fMRI)-assessed blood oxygen-level-dependent (BOLD) response to monetary reward in the dorsomedial prefrontal cortex (dmPFC), the site to which TBS will be administered. Change will be computed as the difference before/after each TBS session, for a total of 3 sessions.

Secondary Outcome Measures

fMRI-assessed dmPFC-VS functional connectivity

Change in fMRI-assessed functional connectivity in response to monetary reward between the dmPFC and the ventral striatum. Change will be computed as the difference before/after each TBS session, for a total of 3 sessions.

Hedonic capacity

Change in self-reported hedonic capacity measured with the Snaith Hamilton Pleasure Scale (14 item measure, with each item rated 1-4 and higher scores indicating greater experience of pleasure; yielding a total score between 14 and 56). Change will be computed as the difference before/after each TBS session, for a total of 3 sessions.

Full Information

NCT ID

NCT03737032

First Posted

October 29, 2018

Last Updated

August 3, 2022

Sponsor

Erika Forbes

Collaborators

National Institute of Mental Health (NIMH)

1. Study Identification

Unique Protocol Identification Number

NCT03737032

Brief Title

Theta Burst Stimulation in Young Adults With Depression

Official Title

Theta Burst Stimulation in Young Adults With Depression

Study Type

Interventional

2. Study Status

Record Verification Date

August 2022

Overall Recruitment Status

Completed

Study Start Date

January 31, 2020 (Actual)

Primary Completion Date

July 31, 2022 (Actual)

Study Completion Date

July 31, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Erika Forbes

Collaborators

National Institute of Mental Health (NIMH)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Yes

Product Manufactured in and Exported from the U.S.

Yes

5. Study Description

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).

Detailed Description

Each participant will undergo 3 sessions of TMS, one each of continuous and intermittent TBS--with the goal of decreasing or increasing dmPFC responding, respectively--and one of sham TBS. Session order will be counterbalanced, with a double-blind approach to condition. Brain function, behavior, and mood will be assessed before and after each TBS session. Broadly, the investigators predict that inhibitory TBS to the dmPFC will enhance neural, behavioral, and subjective aspects of reward function by reducing dmPFC function and dmPFC connectivity with the ventral striatum (VS).

6. Conditions and Keywords

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

Depression

7. Study Design

Primary Purpose

Basic Science

Study Phase

Not Applicable

Interventional Study Model

Crossover Assignment

Model Description

All participants will receive intermittent Theta Burst Stimulation (TBS), continuous TBS, and sham TBS mimicking stimulation, in randomized, double-blind order across three sessions.

Masking

ParticipantOutcomes Assessor

Masking Description

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.

Allocation

Randomized

Enrollment

29 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Intermittent, Continuous, Sham Order

Arm Type

Experimental

Arm Description

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.

Arm Title

Intermittent, Sham, Continuous Order

Arm Type

Experimental

Arm Description

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.

Arm Title

Continuous, Intermittent, Sham Order

Arm Type

Experimental

Arm Description

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.

Arm Title

Continuous, Sham, Intermittent Order

Arm Type

Experimental

Arm Description

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.

Arm Title

Sham, Intermittent, Continuous Order

Arm Type

Experimental

Arm Description

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.

Arm Title

Sham, Continuous, Intermittent Order

Arm Type

Experimental

Arm Description

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.

Intervention Type

Device

Intervention Name(s)

Intermittent Theta Burst Stimulation

Intervention Description

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.

Intervention Type

Device

Intervention Name(s)

Continuous Theta Burst Stimulation

Intervention Description

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.

Intervention Type

Device

Intervention Name(s)

Sham Theta Burst Stimulation

Intervention Description

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.

Primary Outcome Measure Information:

Title

fMRI-assessed brain function in the dorsomedial prefrontal cortex

Description

Time Frame

before and after TBS is administered (1 hour)

Secondary Outcome Measure Information:

Title

fMRI-assessed dmPFC-VS functional connectivity

Description

Time Frame

before and after TBS is administered (1 hour)

Title

Hedonic capacity

Description

Time Frame

before and after TBS is administered (1 hour)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

25 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Erika E Forbes, Ph.D.

Organizational Affiliation

The University of Pittsburgh

Official's Role

Principal Investigator

Facility Information:

Facility Name

The University of Pittsburgh, Department of Psychiatry

City

Pittsburgh

State/Province

Pennsylvania

ZIP/Postal Code

15213

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

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

IPD Sharing 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.

IPD Sharing 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.

Citations:

PubMed Identifier

16262994

Citation

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.

Results Reference

background

PubMed Identifier

16945915

Citation

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.

Results Reference

background

PubMed Identifier

22975030

Citation

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.

Results Reference

background

PubMed Identifier

27918562

Citation

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. Erratum In: Nat Med. 2017 Feb 7;23 (2):264.

Results Reference

background

PubMed Identifier

26327307

Citation

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.

Results Reference

background

PubMed Identifier

21167765

Citation

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.

Results Reference

background

PubMed Identifier

26722001

Citation

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.

Results Reference

background

PubMed Identifier

22117893

Citation

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.

Results Reference

background

PubMed Identifier

19047324

Citation

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.

Results Reference

background

PubMed Identifier

25267639

Citation

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.

Results Reference

background

PubMed Identifier

19070834

Citation

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.

Results Reference

background

PubMed Identifier

19812543

Citation

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.

Results Reference

background

PubMed Identifier

25770818

Citation

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.

Results Reference

background

PubMed Identifier

15664172

Citation

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.

Results Reference

background

PubMed Identifier

28089653

Citation

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.

Results Reference

background

PubMed Identifier

19833552

Citation

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.

Results Reference

background

PubMed Identifier

25797650

Citation

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.

Results Reference

background

PubMed Identifier

7551619

Citation

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.

Results Reference

background

PubMed Identifier

19672310

Citation

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.

Results Reference

background

PubMed Identifier

3397865

Citation

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.

Results Reference

background

PubMed Identifier

23856280

Citation

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.

Results Reference

background

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Theta Burst Stimulation in Young Adults With Depression

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