Treatment, Emotion, and Neuromodulation of Depression (TREND) Study

NCT ID: NCT05436379

Last Updated: 2025-12-30

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

COMPLETED

Clinical Phase

NA

Total Enrollment

21 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-06-17

Study Completion Date

2025-11-30

Brief Summary

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The investigators will administer theta burst stimulation (TBS) in efforts to observe a decrease in severity of reported depression symptoms. A subset of participants will receive positive affect training during this intervention.

Detailed Description

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The study has a longitudinal design in which participants complete a baseline assessment, 20 or 30 theta burst stimulation (TBS) sessions, a post-TBS assessment, and a follow-up assessment 4 months later. Ideally, TBS sessions will be delivered two or three times a day, 5 days/week, for 2 weeks. This procedural design of a shorter treatment duration is based on findings of pattern of improvement and newly developed SAINT protocol. A subset of participants will receive training in enhancing positive affect, with 10 training sessions occurring between pairs of TBS sessions. In this study, "response" to intervention will be defined as a greater than 50% decrease in severity of depression symptoms reported by participants.

Conditions

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Depression

Keywords

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Positive Affect Theta Burst Stimulation

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

The proposed study will use theta burst stimulation (TBS) in an open-label, non-randomized open study for young adults with depression. The study will include measurement of brain function before and after TBS to investigate treatment mechanisms. A subset of participants will also complete a training to enhance positive emotions.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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TBS

In this open-label trial, all participants will undergo 2 or 3 continuous TBS (cTBS) sessions per visit over 10 days (weekdays, over 2 weeks; total = 20 or 30 TBS sessions in 10 visits). The total time of each pair of sessions (including pause between sessions) will be approximately 1 hour, with each session lasting approximately 100 seconds.

There is only 1 group and 1 arm of the study. All participants will receive the treatment.

Group Type OTHER

Theta Burst Stimulation

Intervention Type DEVICE

TBS, a next-gen form of transcranial magnetic stimulation (TMS), requires shorter duration and frequency of stimulation and provides comparable clinical efficacy to traditional repetitive TMS for depression. Thus it is an appropriate technique for use with young adults with depression. TBS can be delivered safely and effectively on an accelerated schedule with two sessions/day. Based on an earlier (ongoing) study of TBS to dorsomedial prefrontal cortex, investigators will administer TBS to dmPFC over 2 weeks in young adults with depression. Addressing the behavioral aspects of anhedonia and reward processing, a subset of participants will also receive positive affect training. Magnetic resonance imaging will guide the personalized location of TBS and will be used to examine change in frontostriatal circuitry with TBS. This study has the potential to influence development of new treatments for depression and anhedonia, with possible mechanisms in frontostriatal brain function.

Interventions

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Theta Burst Stimulation

TBS, a next-gen form of transcranial magnetic stimulation (TMS), requires shorter duration and frequency of stimulation and provides comparable clinical efficacy to traditional repetitive TMS for depression. Thus it is an appropriate technique for use with young adults with depression. TBS can be delivered safely and effectively on an accelerated schedule with two sessions/day. Based on an earlier (ongoing) study of TBS to dorsomedial prefrontal cortex, investigators will administer TBS to dmPFC over 2 weeks in young adults with depression. Addressing the behavioral aspects of anhedonia and reward processing, a subset of participants will also receive positive affect training. Magnetic resonance imaging will guide the personalized location of TBS and will be used to examine change in frontostriatal circuitry with TBS. This study has the potential to influence development of new treatments for depression and anhedonia, with possible mechanisms in frontostriatal brain function.

Intervention Type DEVICE

Eligibility Criteria

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Inclusion Criteria

* Current Diagnostic and Statistical Manual (DSM-5) Depressive Disorder

Exclusion Criteria

* Bipolar disorder (lifetime)
* Obsessive-compulsive disorder (lifetime)
* History of psychosis
* Daily use of nicotine
* Past-month use of cocaine, amphetamines, Methyl enedioxy methamphetamine (MDMA), Phencyclidine (PCP), Ketamine, or gamma-hydroxybutyrate (GHB)
* Past 6 month substance use disorder
* Binge drinking (using NIAAA criteria) within the past week, alcohol use in the past 12 hours
* Neurological disorders: Epilepsy, Parkinson's Disease, brain tumor, brain injury, stroke
* History of head trauma with a loss of consciousness (e.g., concussion)
* History of seizures
* MRI contraindications: body shape/size too large to fit in scanner, claustrophobia, and ferromagnetic metal in the body
* Pregnancy
* Current use of Clozapine, Bupropion, or prescription stimulants
* Current use of benzodiazepines or mood stabilizers
* Body shape/size too large to fit in MRI scanner
* Claustrophobia
* Metal in the head or ferromagnetic metal in the rest of the body
* Implanted medical devices
* High-risk suicidality
Minimum Eligible Age

18 Years

Maximum Eligible Age

26 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Erika Forbes

OTHER

Sponsor Role lead

Responsible Party

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Erika Forbes

Professor

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Erika E Forbes, Ph.D

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh

Locations

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The University of Pittsburgh, Department of Psychiatry

Pittsburgh, Pennsylvania, United States

Site Status

Countries

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United States

References

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Healey KL, Morgan J, Musselman SC, Olino TM, Forbes EE. Social anhedonia and medial prefrontal response to mutual liking in late adolescents. Brain Cogn. 2014 Aug;89:39-50. doi: 10.1016/j.bandc.2013.12.004. Epub 2014 Jan 10.

Reference Type BACKGROUND
PMID: 24412087 (View on PubMed)

Chung SW, Hoy KE, Fitzgerald PB. Theta-burst stimulation: a new form of TMS treatment for depression? Depress Anxiety. 2015 Mar;32(3):182-92. doi: 10.1002/da.22335. Epub 2014 Nov 28.

Reference Type BACKGROUND
PMID: 25450537 (View on PubMed)

Der-Avakian A, Markou A. The neurobiology of anhedonia and other reward-related deficits. Trends Neurosci. 2012 Jan;35(1):68-77. doi: 10.1016/j.tins.2011.11.005. Epub 2011 Dec 15.

Reference Type BACKGROUND
PMID: 22177980 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27918562 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26327307 (View on PubMed)

Forbes EE. Where's the fun in that? Broadening the focus on reward function in depression. Biol Psychiatry. 2009 Aug 1;66(3):199-200. doi: 10.1016/j.biopsych.2009.05.001. No abstract available.

Reference Type BACKGROUND
PMID: 19577042 (View on PubMed)

Kessler RC, Rose S, Koenen KC, Karam EG, Stang PE, Stein DJ, Heeringa SG, Hill ED, Liberzon I, McLaughlin KA, McLean SA, Pennell BE, Petukhova M, Rosellini AJ, Ruscio AM, Shahly V, Shalev AY, Silove D, Zaslavsky AM, Angermeyer MC, Bromet EJ, de Almeida JM, de Girolamo G, de Jonge P, Demyttenaere K, Florescu SE, Gureje O, Haro JM, Hinkov H, Kawakami N, Kovess-Masfety V, Lee S, Medina-Mora ME, Murphy SD, Navarro-Mateu F, Piazza M, Posada-Villa J, Scott K, Torres Y, Carmen Viana M. How well can post-traumatic stress disorder be predicted from pre-trauma risk factors? An exploratory study in the WHO World Mental Health Surveys. World Psychiatry. 2014 Oct;13(3):265-74. doi: 10.1002/wps.20150.

Reference Type BACKGROUND
PMID: 25273300 (View on PubMed)

Morgan JK, Shaw DS, Olino TM, Musselman SC, Kurapati NT, Forbes EE. History of Depression and Frontostriatal Connectivity During Reward Processing in Late Adolescent Boys. J Clin Child Adolesc Psychol. 2016;45(1):59-68. doi: 10.1080/15374416.2015.1030753. Epub 2015 Apr 27.

Reference Type BACKGROUND
PMID: 25915469 (View on PubMed)

Romens SE, Casement MD, McAloon R, Keenan K, Hipwell AE, Guyer AE, Forbes EE. Adolescent girls' neural response to reward mediates the relation between childhood financial disadvantage and depression. J Child Psychol Psychiatry. 2015 Nov;56(11):1177-84. doi: 10.1111/jcpp.12410. Epub 2015 Apr 5.

Reference Type BACKGROUND
PMID: 25846746 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19833552 (View on PubMed)

Rossi S, Antal A, Bestmann S, Bikson M, Brewer C, Brockmoller J, Carpenter LL, Cincotta M, Chen R, Daskalakis JD, Di Lazzaro V, Fox MD, George MS, Gilbert D, Kimiskidis VK, Koch G, Ilmoniemi RJ, Lefaucheur JP, Leocani L, Lisanby SH, Miniussi C, Padberg F, Pascual-Leone A, Paulus W, Peterchev AV, Quartarone A, Rotenberg A, Rothwell J, Rossini PM, Santarnecchi E, Shafi MM, Siebner HR, Ugawa Y, Wassermann EM, Zangen A, Ziemann U, Hallett M; basis of this article began with a Consensus Statement from the IFCN Workshop on "Present, Future of TMS: Safety, Ethical Guidelines", Siena, October 17-20, 2018, updating through April 2020. Safety and recommendations for TMS use in healthy subjects and patient populations, with updates on training, ethical and regulatory issues: Expert Guidelines. Clin Neurophysiol. 2021 Jan;132(1):269-306. doi: 10.1016/j.clinph.2020.10.003. Epub 2020 Oct 24.

Reference Type BACKGROUND
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Reference Type BACKGROUND
PMID: 25797650 (View on PubMed)

Other Identifiers

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STUDY21060041

Identifier Type: -

Identifier Source: org_study_id