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E-field Guided iTBS for Treatment Resistant Depression

Primary Purpose

Major Depressive Disorder

Status
Recruiting
Phase
Not Applicable
Locations
Canada
Study Type
Interventional
Intervention
iTBS
Sponsored by
Centre for Addiction and Mental Health
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Major Depressive Disorder focused on measuring brain stimulation, rTMS

Eligibility Criteria

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

Inclusion Criteria:

  1. are outpatients;
  2. are voluntary and competent to consent to treatment;
  3. have a Diagnostic and Statistical Manual for Mental Disorders, 5th edition major depressive episode based on the Mini International Neuropsychiatric Interview (MINI)
  4. are 18yo to 65yo;
  5. have a score of ≥18 on the Hamilton Rating Scale for Depression (HRSD-17) item at screening
  6. have not had a clinical response to an adequate dose of an antidepressant based on an Antidepressant Treatment History Form (ATHF) score of ≥ 3 in the current episode or have been unable to tolerate at least 2 separate trials of antidepressants of inadequate dose and duration (ATHF 1 or 2);
  7. are agreeable to keeping their current medication constant during the study
  8. are able to adhere to the study and treatment schedules
  9. meet TMS and MRI safety criteria

Exclusion Criteria:

  1. have a concomitant unstable medical illness
  2. are pregnant or intend to become pregnant during the study
  3. have a current MINI diagnosis of bipolar disorder, psychotic disorder, obsessive compulsive disorder, concurrent substance use disorder (aside from nicotine) or post-traumatic stress disorder (current or within the last year)
  4. have failed a course of electroconvulsive therapy within the current depressive episode due to the lower likelihood of response to rTMS;
  5. have any significant neurological disorder (e.g., space occupying brain lesion, history of stroke, cerebral aneurysm, seizure disorder, Parkinson's disease, Huntington's chorea, multiple sclerosis) or confirmed diagnosis of dementia or cognitive impairment
  6. present with a medical condition, medication, or laboratory abnormality that could cause a major depressive episode in the opinion of the investigator
  7. have an intracranial implant or any other metal object that cannot be safely removed, precluding safety of TMS or MRI exposure within or near the head, excluding the mouth
  8. require benzodiazepine equivalent to lorazepam 2 mg/day or higher or any anticonvulsant due to the potential of these medications to limit the efficacy of rTMS [45]
  9. have inadequate English fluency to complete clinical assessments.
  10. are participating in a new course psychotherapy initiated within the last 3 months or finishing prior to the end of scheduled treatments;
  11. have a non-correctable clinically significant sensory impairment (i.e., cannot hear well enough to cooperate with interview).

Sites / Locations

  • Poul Hansen Family Centre for Depression, Toronto Western HospitalRecruiting
  • Centre for Addiction and Mental HealthRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Treatment Course A: E-field Modeling

Treatment Course B: Beam F3

Arm Description

Your Magnetic Resonance Image (MRI) results and rTMS calibration information (motor threshold) will be used to create a brain model and identify the targeted location, iTBS coil position and intensity for your iTBS rTMS treatment. You will undergo iTBS rTMS treatment in this study for 6 weeks. There will be 5 iTBS treatment sessions per week, lasting approximately 3 minutes each, once daily for 5 days in a row (always Monday to Friday). Each day after treatment, you will also complete a brief set of questionnaires to track your symptoms, which will take 15 minutes. After every 5 treatments, you will complete an extra interview that will take an additional 30 minutes. There will also be two follow-up visits at 1 and 4 weeks after the end of treatment, each lasting approximately 1 hour. During these follow-up visits, you will be asked to complete a brief set of questionnaires and interviews to monitor your symptoms.

The targeted iTBS rTMS treatment location and intensity will be determined via standard parameters, specifically anatomical landmarks and your rTMS calibration information (motor threshold). You will undergo iTBS rTMS treatment in this study for 6 weeks. There will be 5 iTBS treatment sessions per week, lasting approximately 3 minutes each, once daily for 5 days in a row (always Monday to Friday). Each day after treatment, you will also complete a brief set of questionnaires to track your symptoms, which will take 15 minutes. After every 5 treatments, you will complete an extra interview that will take an additional 30 minutes. There will also be two follow-up visits at 1 and 4 weeks after the end of treatment, each lasting approximately 1 hour. During these follow-up visits, you will be asked to complete a brief set of questionnaires and interviews to monitor your symptoms.

Outcomes

Primary Outcome Measures

Markers of cortical excitation
TMS-EEG markers of increased cortical excitation (GMFA-AUC)
Depression scores
Hamilton depression rating scale (HDRS-17) scores

Secondary Outcome Measures

Peripheral biomarkers
Circulating volumes of gamma-aminobutyric acid (GABA), brain-derived neurotrophic factor (BDNF) and N-methyl-D-aspartate (NMDA) proteins

Full Information

First Posted
June 8, 2022
Last Updated
September 25, 2023
Sponsor
Centre for Addiction and Mental Health
Collaborators
University Health Network, Toronto
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1. Study Identification

Unique Protocol Identification Number
NCT05583747
Brief Title
E-field Guided iTBS for Treatment Resistant Depression
Official Title
Electrical Field Modeling to Engage Neurophysiological Targets of Intermittent Theta Burst Stimulation in Treatment Resistant Depression (E-Fields iTBS)
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 24, 2022 (Actual)
Primary Completion Date
March 31, 2027 (Anticipated)
Study Completion Date
July 31, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Centre for Addiction and Mental Health
Collaborators
University Health Network, Toronto

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this study is to establish how personalization of repetitive transcranial magnetic stimulation (rTMS) can change markers of brain activity and improve treatment response. To do this, all participants will receive the same active form of treatments, but some of the participants in this study will receive intermittent theta burst stimulation (iTBS) rTMS treatment with standard forms of targeting and intensity, and others will receive iTBS rTMS treatment using personalized magnetic resonance imaging (MRI) and electric field (E-field) modeling measures.
Detailed Description
The purpose of this study is to establish how personalization of rTMS can change markers of brain activity and improve treatment response in major depressive disorder (MDD). All participants will receive up to 30 iTBS treatments to the left dorsolateral prefrontal cortex (DLPFC), delivered daily, 5 days per week, for 6 weeks. Participants will be randomized to either a standard treatment arm, in which the iTBS targeting will be via the Beam F3 method to identify the left DLPFC location, and intensity will be determined as 120% of the resting motor threshold, or a personalized arm, in which the left DLPFC will be identified via functional magnetic resonance imaging (fMRI), the optimal coil position and stimulus intensity will be derived through E-Field modeling pipelines.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Major Depressive Disorder
Keywords
brain stimulation, rTMS

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderOutcomes Assessor
Allocation
Randomized
Enrollment
110 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treatment Course A: E-field Modeling
Arm Type
Experimental
Arm Description
Your Magnetic Resonance Image (MRI) results and rTMS calibration information (motor threshold) will be used to create a brain model and identify the targeted location, iTBS coil position and intensity for your iTBS rTMS treatment. You will undergo iTBS rTMS treatment in this study for 6 weeks. There will be 5 iTBS treatment sessions per week, lasting approximately 3 minutes each, once daily for 5 days in a row (always Monday to Friday). Each day after treatment, you will also complete a brief set of questionnaires to track your symptoms, which will take 15 minutes. After every 5 treatments, you will complete an extra interview that will take an additional 30 minutes. There will also be two follow-up visits at 1 and 4 weeks after the end of treatment, each lasting approximately 1 hour. During these follow-up visits, you will be asked to complete a brief set of questionnaires and interviews to monitor your symptoms.
Arm Title
Treatment Course B: Beam F3
Arm Type
Active Comparator
Arm Description
The targeted iTBS rTMS treatment location and intensity will be determined via standard parameters, specifically anatomical landmarks and your rTMS calibration information (motor threshold). You will undergo iTBS rTMS treatment in this study for 6 weeks. There will be 5 iTBS treatment sessions per week, lasting approximately 3 minutes each, once daily for 5 days in a row (always Monday to Friday). Each day after treatment, you will also complete a brief set of questionnaires to track your symptoms, which will take 15 minutes. After every 5 treatments, you will complete an extra interview that will take an additional 30 minutes. There will also be two follow-up visits at 1 and 4 weeks after the end of treatment, each lasting approximately 1 hour. During these follow-up visits, you will be asked to complete a brief set of questionnaires and interviews to monitor your symptoms.
Intervention Type
Device
Intervention Name(s)
iTBS
Intervention Description
rTMS involves direct stimulation of cortical neurons using externally applied, powerful, focused magnetic field pulses. iTBS is a briefer form of patterned rTMS that has been shown to be effective against MDD, despite a stimulation period of 1-3 min rather than 30-40 min.
Primary Outcome Measure Information:
Title
Markers of cortical excitation
Description
TMS-EEG markers of increased cortical excitation (GMFA-AUC)
Time Frame
change from pre-intervention to post-intervention (average of 6 weeks)
Title
Depression scores
Description
Hamilton depression rating scale (HDRS-17) scores
Time Frame
changes from baseline to Week 4 follow-up
Secondary Outcome Measure Information:
Title
Peripheral biomarkers
Description
Circulating volumes of gamma-aminobutyric acid (GABA), brain-derived neurotrophic factor (BDNF) and N-methyl-D-aspartate (NMDA) proteins
Time Frame
change from Pre- and post-intervention (average of 6 weeks)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: are outpatients; are voluntary and competent to consent to treatment; have a Diagnostic and Statistical Manual for Mental Disorders, 5th edition major depressive episode based on the Mini International Neuropsychiatric Interview (MINI) are 18yo to 65yo; have a score of ≥18 on the Hamilton Rating Scale for Depression (HRSD-17) item at screening have not had a clinical response to an adequate dose of an antidepressant based on an Antidepressant Treatment History Form (ATHF) score of ≥ 3 in the current episode or have been unable to tolerate at least 2 separate trials of antidepressants of inadequate dose and duration (ATHF 1 or 2); are agreeable to keeping their current medication constant during the study are able to adhere to the study and treatment schedules meet TMS and MRI safety criteria Exclusion Criteria: have a concomitant unstable medical illness are pregnant or intend to become pregnant during the study have a current MINI diagnosis of bipolar disorder, psychotic disorder, obsessive compulsive disorder, concurrent substance use disorder (aside from nicotine) or post-traumatic stress disorder (current or within the last year) have failed a course of electroconvulsive therapy within the current depressive episode due to the lower likelihood of response to rTMS; have any significant neurological disorder (e.g., space occupying brain lesion, history of stroke, cerebral aneurysm, seizure disorder, Parkinson's disease, Huntington's chorea, multiple sclerosis) or confirmed diagnosis of dementia or cognitive impairment present with a medical condition, medication, or laboratory abnormality that could cause a major depressive episode in the opinion of the investigator have an intracranial implant or any other metal object that cannot be safely removed, precluding safety of TMS or MRI exposure within or near the head, excluding the mouth require benzodiazepine equivalent to lorazepam 2 mg/day or higher or any anticonvulsant due to the potential of these medications to limit the efficacy of rTMS [45] have inadequate English fluency to complete clinical assessments. are participating in a new course psychotherapy initiated within the last 3 months or finishing prior to the end of scheduled treatments; have a non-correctable clinically significant sensory impairment (i.e., cannot hear well enough to cooperate with interview).
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Daphne Voineskos, MD
Phone
416-535-8501
Ext
30176
Email
daphne.voineskos@camh.ca
Facility Information:
Facility Name
Poul Hansen Family Centre for Depression, Toronto Western Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5T 2S8
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Eileen Lam
Email
eileen.lam@uhn.ca
First Name & Middle Initial & Last Name & Degree
Daphne Voineskos, MD, Phd, FRCPC
Facility Name
Centre for Addiction and Mental Health
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M6J 1H4
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Daphne Voineskos, MD, PhD, FRCPC
Phone
416-535-8501
Ext
30176
Email
daphne.voineskos@camh.ca
First Name & Middle Initial & Last Name & Degree
Daphne Voineskos, MDP, PhD, FRCPC

12. IPD Sharing Statement

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E-field Guided iTBS for Treatment Resistant Depression

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