Using Multiple Brain-based Biomarkers to Validate and Predict Response to Theta Burst Stimulation as a New Treatment for Major Depressive Disorder

Biomarkers of Theta Burst Stimulation in Major Depressive Disorder



Sponsors

Lead Sponsor



Source

University of Calgary

Oversight Info

Has Dmc

No

Is Fda Regulated Drug

No

Is Fda Regulated Device

No

Is Us Export

No


Brief Summary

This study investigates the brain-based biomarkers of treatment response to accelerated theta
burst stimulation (aTBS) in patients with Major Depressive Disorder resistant to
pharmacological treatment(MDD) in an open label design.

Detailed Description

Theta burst stimulation (TBS) is a newer form of rTMS which requires less stimulation time
and produces longer lasting post-stimulation effects in the cerebral cortex (4). It has been
shown to be effective in inducing synaptic plasticity and has similar or better efficacy in
treating depression compared to rTMS (4).Newer accelerated TBS (aTBS) protocols that condense
stimulation sessions down to several days rather than weeks have shown similar response rates
when compared to prolonged TBS protocols, also with similar tolerability and safety. In order
to develop aTBS as an effective treatment for MDD, future research should focus on
identification of reliable predictors for better outcome to TBS. The main objectives were: 1)
To directly compare multiple different brain-based measures (neuroimaging and
electrophysiology) to identify which has the most power in accurately predicting response to
TBS compared to sham. 2) To track both short and long-term longitudinal electrophysiological
(EEG) changes related to the therapeutic effects of TBS.

Overall Status

Recruiting

Start Date

2018-07-06

Completion Date

2019-07-01

Primary Completion Date

2019-07-01

Phase

N/A

Study Type

Interventional

Primary Outcome

Measure

Time Frame

Hamilton Depression Rating Scale
Change from baseline at 5 days of TBS treatment

Secondary Outcome

Measure

Time Frame

1. Montgomery-Åsberg Depression Rating Scale (MADRS)
Change from baseline at 5 days of TBS treatment
2. Hamilton Anxiety rating Scale (HAM-A)
Change from baseline at 5 days of TBS treatment
2. Columbia Suicide Severity Rating Scale ( CSSRS)
Change from baseline at 5 days of TBS treatment
MGH Rumination questionnaire
Change from baseline at 5 days of TBS treatment
Snaith-Hamilton Pleasure scale-Clinician administered (SHAP-C)
Change from baseline at 5 days of TBS treatment
36 item short form survey (SF-36)
Change from baseline at 5 days of TBS treatment
Global Assessment of Functioning (GAF)
Change from baseline at 5 days of TBS treatment
Resting state functional connectivity-Functional magnetic resonance imaging (rsfMRI)
Pretreatment baseline
Magnetic resonance spectroscopy (MRS)
Pretreatment baseline
Electroencephalogram
Change from baseline at 5 days of TBS treatment

Enrollment

30

Condition


Intervention

Intervention Type

Device

Intervention Name


Description

Participants will receive bilateral TBS, 5 times daily (15 minutes between), over 5 consecutive days (25 sessions total). In each session they will receive intermittent TBS (iTBS) over left dorsolateral prefrontal cortex (DLPFC), followed by continuous TBS (cTBS) over right DLPFC. Stimulation sites will be targeted with the Localite neuronavigation system and Visor2 software, and according to Talairach coordinates in relation to individual MRIs. Intensity will be standardized at 120% of RMT.
The MagPro stimulator will deliver iTBS over left DLPFC with 1620 pulses in 54 triplet bursts (5Hz) with train duration of 2 seconds, and intertrain interval of 8 seconds. cTBS over right DLPFC will consist of 1620 pulses in 54 triplet bursts, train duration of 2 seconds, with no intertrain interval.

Arm Group Label

Active TBS-DLPFC


Eligibility

Criteria

Inclusion Criteria:

1. Participant must meet the DSM-5 diagnostic criteria for single-episode Major
Depressive Disorder (MDD).

2. Participant must have failed to respond to >1 but <4 classes of oral antidepressant
treatments in the current episode of depression.

3. Participant must have a HAMD total score of at least 18

Exclusion Criteria:

1. The participant's depressive symptoms have previously demonstrated nonresponse to:

- An adequate course of rTMS/TBS over DLPFC in the current major depressive
episode, defined as at least 3 weeks of treatment, 5 times weekly

- An adequate course of treatment with electroconvulsive therapy (ECT) in the
current major depressive episode, defined as at least 7 treatments with
unilateral/bilateral ECT.

2. Participant has received vagal nerve stimulation (VNS) or has received deep brain
stimulation (DBS) in the current episode of depression.

3. Participant has a current or prior DSM-5 diagnosis of Axis I comorbidities, including
psychosis, bipolar disorder, obsessive compulsive disorder, based upon clinical
assessment and confirmed by the MINI.

4. Participant has a current or prior DSM-5 diagnosis of Axis II comorbidities, including
severe borderline personality disorders, antisocial, schizotypal, schizoid personality
disorders based upon clinical assessment and confirmed by the MINI.

5. Participant has severe suicidal ideation/plan/ intent.

6. Participant has a history of moderate or severe substance or alcohol use disorder
according to DSM-5 criteria.

7. Participant has a current or past history of seizures and neurological problems, e.g.
head injury, stroke, progressive neurological disorder and complicated and unstable
medical disorders, e.g. cardiovascular-related conditions, diabetes.

Gender

All

Minimum Age

18 Years

Maximum Age

65 Years

Healthy Volunteers

No


Overall Official

Last Name

Role

Affiliation

Rajamannar Ramasubbu, MD,FRCPC,MSc
Principal Investigator
University of Calgary, Department of Psychiatry

Overall Contact

Last Name

Rajamannar Ramasubbu, MD,FRCPC,MSc

Phone

403-210-6890

Email



Location

Facility

Status

University of Calgary
Calgary Alberta T2N 4Z6 Canada
Recruiting

Location Countries

Country

Canada


Verification Date

2018-08-01

Lastchanged Date

N/A

Firstreceived Date

N/A

Responsible Party

Responsible Party Type

Principal Investigator

Investigator Affiliation

University of Calgary

Investigator Full Name

Rajamannar Ramasubbu

Investigator Title

Professor


Has Expanded Access

No

Condition Browse


Secondary Id

RT # 10016954

Number Of Arms

1

Arm Group

Arm Group Label

Active TBS-DLPFC

Arm Group Type

Experimental

Description

There is only one arm. All participants will receive Theta Burst Stimulation (transcranial magnetic stimulation) of the dorsolateral prefrontal cortex.


Results Reference

Citation

Duprat R, Desmyter S, Rudi de R, van Heeringen K, Van den Abbeele D, Tandt H, Bakic J, Pourtois G, Dedoncker J, Vervaet M, Van Autreve S, Lemmens GM, Baeken C. Accelerated intermittent theta burst stimulation treatment in medication-resistant major depression: A fast road to remission? J Affect Disord. 2016 Aug;200:6-14. doi: 10.1016/j.jad.2016.04.015. Epub 2016 Apr 19.

PMID

27107779


Citation

Desmyter S, Duprat R, Baeken C, Van Autreve S, Audenaert K, van Heeringen K. Accelerated Intermittent Theta Burst Stimulation for Suicide Risk in Therapy-Resistant Depressed Patients: A Randomized, Sham-Controlled Trial. Front Hum Neurosci. 2016 Sep 27;10:480. eCollection 2016.

PMID

27729854


Citation

Fitzgerald PB, Hoy KE, Elliot D, Susan McQueen RN, Wambeek LE, Daskalakis ZJ. Accelerated repetitive transcranial magnetic stimulation in the treatment of depression. Neuropsychopharmacology. 2018 Jun;43(7):1565-1572. doi: 10.1038/s41386-018-0009-9. Epub 2018 Feb 5.

PMID

29467437


Citation

Holtzheimer PE 3rd, McDonald WM, Mufti M, Kelley ME, Quinn S, Corso G, Epstein CM. Accelerated repetitive transcranial magnetic stimulation for treatment-resistant depression. Depress Anxiety. 2010 Oct;27(10):960-3. doi: 10.1002/da.20731.

PMID

20734360


Citation

Li CT, Chen MH, Juan CH, Huang HH, Chen LF, Hsieh JC, Tu PC, Bai YM, Tsai SJ, Lee YC, Su TP. Efficacy of prefrontal theta-burst stimulation in refractory depression: a randomized sham-controlled study. Brain. 2014 Jul;137(Pt 7):2088-98. doi: 10.1093/brain/awu109. Epub 2014 May 10.

PMID

24817188


Citation

Oberman L, Edwards D, Eldaief M, Pascual-Leone A. Safety of theta burst transcranial magnetic stimulation: a systematic review of the literature. J Clin Neurophysiol. 2011 Feb;28(1):67-74. doi: 10.1097/WNP.0b013e318205135f. Review.

PMID

21221011


Citation

Bakker N, Shahab S, Giacobbe P, Blumberger DM, Daskalakis ZJ, Kennedy SH, Downar J. rTMS of the dorsomedial prefrontal cortex for major depression: safety, tolerability, effectiveness, and outcome predictors for 10 Hz versus intermittent theta-burst stimulation. Brain Stimul. 2015 Mar-Apr;8(2):208-15. doi: 10.1016/j.brs.2014.11.002. Epub 2014 Nov 6.

PMID

25465290


Citation

Blumberger DM, Maller JJ, Thomson L, Mulsant BH, Rajji TK, Maher M, Brown PE, Downar J, Vila-Rodriguez F, Fitzgerald PB, Daskalakis ZJ. Unilateral and bilateral MRI-targeted repetitive transcranial magnetic stimulation for treatment-resistant depression: a randomized controlled study. J Psychiatry Neurosci. 2016 Jun;41(4):E58-66.

PMID

27269205


Citation

Brunoni AR, Chaimani A, Moffa AH, Razza LB, Gattaz WF, Daskalakis ZJ, Carvalho AF. Repetitive Transcranial Magnetic Stimulation for the Acute Treatment of Major Depressive Episodes: A Systematic Review With Network Meta-analysis. JAMA Psychiatry. 2017 Feb 1;74(2):143-152. doi: 10.1001/jamapsychiatry.2016.3644. Review.

PMID

28030740


Citation

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. Review.

PMID

25450537



Firstreceived Results Date

N/A

Overall Contact Backup

Last Name

Laina B McAusland, RN,MSc

Phone

403-210-6905

Email



Firstreceived Results Disposition Date

N/A

Study Design Info

Intervention Model

Single Group Assignment

Intervention Model Description

Open label study

Primary Purpose

Treatment

Masking

None (Open Label)


Study First Submitted

July 4, 2018

Study First Submitted Qc

August 7, 2018

Study First Posted

August 10, 2018

Last Update Submitted

August 7, 2018

Last Update Submitted Qc

August 7, 2018

Last Update Posted

August 10, 2018


ClinicalTrials.gov processed this data on August 27, 2018

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Interventions

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Study Phase

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In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.

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