Theta Burst Stimulation in Young Adults With Depression

Depression Clinical Trial

Official title:

Theta Burst Stimulation in Young Adults With Depression

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03737032
• Other study ID #: PRO18040159
• Secondary ID: R21MH117400
• Status: Completed
• Phase: N/A
• Start date: January 31, 2020
• Est. completion date: July 31, 2022

Study information

• Verified date: February 2024
• Source: University of Pittsburgh
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 29
• Est. completion date: July 31, 2022
• Est. primary completion date: July 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 25 Years

Eligibility

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

Related Conditions & MeSH terms

• Depression
• Depressive Disorder

Intervention

Device:
• Intermittent Theta Burst Stimulation
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 Theta Burst Stimulation
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.
• Sham Theta Burst Stimulation
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.

Locations

Country	Name	City	State
United States	The University of Pittsburgh, Department of Psychiatry	Pittsburgh	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Erika Forbes	National Institute of Mental Health (NIMH)

Country where clinical trial is conducted

United States, 

References & Publications (21)

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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. — View 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. — View Citation

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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. — View 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. — View 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. — View 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. — View 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. — View Citation

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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. — View 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. — View 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. — View Citation

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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. — View 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. — View Citation

* Note: There are 21 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Positive Affect	Self-reported pleasant mood was measured with the Positive Affect (PA) scale of the Positive and Negative Affect Schedule (PANAS). This scale consists of a number of words that describe different feelings and emotions, participants are instructed to read each item and then mark to which extent they have felt like this in the past few hours. The PA scale contains 10 items, with each item rated on a 5-point scale of 1 (very slightly or not at all), 2 (a little), 3 (moderately), 4 (quite a bit), or 5 (extremely). Higher scores indicate greater PA. The total PA score is calculated by finding the sum of the 10 positive items. Scores range from 10-50. A higher score indicates higher intensity of positive affect. The PANAS PA data analyzed were from administrations pre- and post-TBS at visits #3-5 (approximately 30 minutes before and 1 hour after TBS administration).	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.
Secondary	VS-dmPFC Functional Connectivity	Outcome measure is assessed with functional magnetic resonance imaging (fMRI), in which brain function is recorded during a reward task. Functional connectivity between 2 regions of neural reward circuitry, the ventral striatum (VS) and the dorsomedial prefrontal cortex (dmPFC), is computed using general psychophysiologic interaction for this pair of regions in Statistical Parametric Mapping software. FC data are in arbitrary units, with higher values reflecting higher degree of coordination between the regions. Theoretical minimum and maximum scores do not exist. Higher scores do not represent "better" or "worse" outcomes or change in health. Based on study hypotheses, FC is predicted to decrease with continuous TBS, based on significance of statistical tests.	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.