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Biomarkers of Theta Burst Stimulation in Major Depressive Disorder

Primary Purpose

Depressive Disorder, Treatment-Resistant

Status

Unknown status

Phase

Not Applicable

Locations

Canada

Study Type

Interventional

Intervention

Theta Burst Stimulation ( Transcranial Magnetic Stimulation)

About this trial

This is an interventional treatment trial for Depressive Disorder, Treatment-Resistant

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Participant must meet the DSM-5 diagnostic criteria for single-episode Major Depressive Disorder (MDD).
Participant must have failed to respond to >1 but <4 classes of oral antidepressant treatments in the current episode of depression.
Participant must have a HAMD total score of at least 18

Exclusion Criteria:

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.
Participant has received vagal nerve stimulation (VNS) or has received deep brain stimulation (DBS) in the current episode of depression.
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.
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.
Participant has severe suicidal ideation/plan/ intent.
Participant has a history of moderate or severe substance or alcohol use disorder according to DSM-5 criteria.
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.

Sites / Locations

University of CalgaryRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Active TBS-DLPFC

Arm Description

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

Outcomes

Primary Outcome Measures

Hamilton Depression Rating Scale

Clinician administered questionnaire to asses clinical improvement and classify response and remission

Secondary Outcome Measures

1. Montgomery-Åsberg Depression Rating Scale (MADRS)

A ten item clinician administered questionnaire to measure the severity of depressive symptoms on a 0 to 6 severity scale with higher scores indicating more severe depressive symptoms. Cut-off points include: 0 to 6 - symptom absent, 7 to 19 - mild depression, 30 to 34 - moderate, 35 to 60 - severe depression.

2. Hamilton Anxiety rating Scale (HAM-A)

A rating scale to measure the severity of anxiety symptoms. Each item is scored on a scale of 0 (not present) to 4 (severe), with a total score range of 0-56, where <17 indicates mild severity, 18-24 mild to moderate severity and 25-30 moderate to severe.

2. Columbia Suicide Severity Rating Scale ( CSSRS)

A suicidal rating scale devised by researchers at Columbia University. The presence of suicidal ideation score ranges from 1-5 and the intensity of the suicidal ideation ranges from 0-25 with higher scores indicating higher levels of intensity.

MGH Rumination questionnaire

Self administered 9 items scale to measure the severity of rumination. Each item is measured from 0-4 with a total score range of 0-36. Higher scores indicate more severe rumination.

Snaith-Hamilton Pleasure scale-Clinician administered (SHAP-C)

This is to evaluate the ability to enjoy/experience pleasure. Each item can score 0 or 1 with a total score possibility of 0-14. Higher scores represent higher anhedonia and 3 or over is considered abnormal.

36 item short form survey (SF-36)

This is to evaluate physical and emotional health.

Global Assessment of Functioning (GAF)

This is to evaluate psychological, social and occupational functioning

Resting state functional connectivity-Functional magnetic resonance imaging (rsfMRI)

Temporal correlation of brain signals as measured by BOLD signals

Magnetic resonance spectroscopy (MRS)

To measure glutathione and glutamate concentration in DLPFC and ACC

Electroencephalogram

To measure neuronal oscillations

Full Information

NCT ID

NCT03626181

First Posted

July 4, 2018

Last Updated

August 7, 2018

Sponsor

University of Calgary

1. Study Identification

Unique Protocol Identification Number

NCT03626181

Brief Title

Biomarkers of Theta Burst Stimulation in Major Depressive Disorder

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2018

Overall Recruitment Status

Unknown status

Study Start Date

July 6, 2018 (Actual)

Primary Completion Date

July 1, 2019 (Anticipated)

Study Completion Date

July 1, 2019 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of Calgary

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

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

Depressive Disorder, Treatment-Resistant

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Model Description

Open label study

Masking

None (Open Label)

Allocation

N/A

Enrollment

30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Active TBS-DLPFC

Arm Type

Experimental

Arm Description

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

Intervention Type

Device

Intervention Name(s)

Theta Burst Stimulation ( Transcranial Magnetic Stimulation)

Intervention 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.

Primary Outcome Measure Information:

Title

Hamilton Depression Rating Scale

Description

Clinician administered questionnaire to asses clinical improvement and classify response and remission

Time Frame

Change from baseline at 5 days of TBS treatment

Secondary Outcome Measure Information:

Title

1. Montgomery-Åsberg Depression Rating Scale (MADRS)

Description

Time Frame

Change from baseline at 5 days of TBS treatment

Title

2. Hamilton Anxiety rating Scale (HAM-A)

Description

Time Frame

Change from baseline at 5 days of TBS treatment

Title

2. Columbia Suicide Severity Rating Scale ( CSSRS)

Description

Time Frame

Change from baseline at 5 days of TBS treatment

Title

MGH Rumination questionnaire

Description

Self administered 9 items scale to measure the severity of rumination. Each item is measured from 0-4 with a total score range of 0-36. Higher scores indicate more severe rumination.

Time Frame

Change from baseline at 5 days of TBS treatment

Title

Snaith-Hamilton Pleasure scale-Clinician administered (SHAP-C)

Description

Time Frame

Change from baseline at 5 days of TBS treatment

Title

36 item short form survey (SF-36)

Description

This is to evaluate physical and emotional health.

Time Frame

Change from baseline at 5 days of TBS treatment

Title

Global Assessment of Functioning (GAF)

Description

This is to evaluate psychological, social and occupational functioning

Time Frame

Change from baseline at 5 days of TBS treatment

Title

Resting state functional connectivity-Functional magnetic resonance imaging (rsfMRI)

Description

Temporal correlation of brain signals as measured by BOLD signals

Time Frame

Pretreatment baseline

Title

Magnetic resonance spectroscopy (MRS)

Description

To measure glutathione and glutamate concentration in DLPFC and ACC

Time Frame

Pretreatment baseline

Title

Electroencephalogram

Description

To measure neuronal oscillations

Time Frame

Change from baseline at 5 days of TBS treatment

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Participant must meet the DSM-5 diagnostic criteria for single-episode Major Depressive Disorder (MDD). Participant must have failed to respond to >1 but <4 classes of oral antidepressant treatments in the current episode of depression. Participant must have a HAMD total score of at least 18 Exclusion Criteria: 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. Participant has received vagal nerve stimulation (VNS) or has received deep brain stimulation (DBS) in the current episode of depression. 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. 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. Participant has severe suicidal ideation/plan/ intent. Participant has a history of moderate or severe substance or alcohol use disorder according to DSM-5 criteria. 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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Rajamannar Ramasubbu, MD,FRCPC,MSc

Phone

403-210-6890

rramasub@ucalgary.ca

First Name & Middle Initial & Last Name or Official Title & Degree

Laina B McAusland, RN,MSc

Phone

403-210-6905

lbsorens@ucalgary.ca

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Rajamannar Ramasubbu, MD,FRCPC,MSc

Organizational Affiliation

University of Calgary, Department of Psychiatry

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Calgary

City

Calgary

State/Province

Alberta

ZIP/Postal Code

T2N 4Z6

Country

Canada

Individual Site Status

Recruiting

12. IPD Sharing Statement

Citations:

PubMed Identifier

27107779

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.

Results Reference

result

PubMed Identifier

27729854

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. doi: 10.3389/fnhum.2016.00480. eCollection 2016.

Results Reference

result

PubMed Identifier

29467437

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.

Results Reference

result

PubMed Identifier

20734360

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.

Results Reference

result

PubMed Identifier

24817188

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.

Results Reference

result

PubMed Identifier

21221011

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.

Results Reference

result

PubMed Identifier

25465290

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.

Results Reference

result

PubMed Identifier

27269205

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. doi: 10.1503/jpn.150265.

Results Reference

result

PubMed Identifier

28030740

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. Erratum In: JAMA Psychiatry. 2017 Apr 1;74(4):424.

Results Reference

result

PubMed Identifier

25450537

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.

Results Reference

result

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Biomarkers of Theta Burst Stimulation in Major Depressive Disorder

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