Major Depressive DisorderNCT05583747
E-field Guided iTBS for Treatment Resistant Depression
A study testing iTBS in people with Major Depressive Disorder, run by Centre for Addiction and Mental Health at 2 sites in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Major Depressive Disorder
- What is being tested?
- iTBS
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 110 participants
- Where
- 2 sitesCanada
- Study dates
- 24 Oct 2022to 31 Jul 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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);
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- 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
Who cannot join
- 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
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- 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).
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Canada2 sites, 2 recruiting
- Recruiting
Poul Hansen Family Centre for Depression, Toronto Western Hospital
Toronto, Ontario, M5T 2S8
Eileen Lam, eileen.lam@uhn.ca
Daphne Voineskos, MD, Phd, FRCPC
- Recruiting
Centre for Addiction and Mental Health
Toronto, Ontario, M6J 1H4
Daphne Voineskos, MD, PhD, FRCPC, 416-535-8501 ext. 30176, daphne.voineskos@camh.ca
Daphne Voineskos, MDP, PhD, FRCPC
About this study
Official title: Electrical Field Modeling to Engage Neurophysiological Targets of Intermittent Theta Burst Stimulation in Treatment Resistant Depression (E-Fields iTBS)
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.
Read the 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.
- Conditions
- Major Depressive Disorder
- Being tested
- iTBS
- Keywords
- brain stimulation, rTMS
- Medical subject headings
- Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
iTBSDevice
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.
| Study group | Role | What they receive |
|---|---|---|
| Treatment Course A: E-field Modeling | Experimental | 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. Receives: Device: iTBS |
| Treatment Course B: Beam F3 | Active comparator | 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. Receives: Device: iTBS |
What is being measured
The primary outcome is the main question the study is designed to answer.
Markers of cortical excitation
TMS-EEG markers of increased cortical excitation (GMFA-AUC)
Measured: change from pre-intervention to post-intervention (average of 6 weeks)
Depression scores
Hamilton depression rating scale (HDRS-17) scores
Measured: changes from baseline to Week 4 follow-up
Secondary outcomes (1)
Peripheral biomarkers
Circulating volumes of gamma-aminobutyric acid (GABA), brain-derived neurotrophic factor (BDNF) and N-methyl-D-aspartate (NMDA) proteins
Measured: change from Pre- and post-intervention (average of 6 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Oct 2022
- Study start24 Oct 2022
- Primary completion31 Mar 2027 (estimated)
- Study completion31 Jul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 110 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Centre for Addiction and Mental Health
- Sponsor type
- University, hospital or other
- Collaborators
- University Health Network, Toronto
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05583747
- Sponsor's protocol ID
- 3773
- Status last verified
- Sep 2023
- First submitted
- 8 Jun 2022
- Last updated
- 26 Sep 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Electrical Field Modeling to Engage Neurophysiological Targets of Intermittent Theta Burst Stimulation in Treatment Resistant Depression (E-Fields iTBS)
- ClinicalTrials.gov ID
- NCT05583747
- Acronym / sponsor ID
- 3773
- Conditions
- Major Depressive Disorder
- Keywords
- brain stimulation, rTMS
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 110 participants (estimated)
- Lead sponsor
- Centre for Addiction and Mental HealthUniversity, hospital or other
- Collaborators
- University Health Network, Toronto
- Study start
- 24 Oct 2022 (actual)
- Primary completion
- 31 Mar 2027 (estimated)
- Study completion
- 31 Jul 2027 (estimated)
- First posted
- 18 Oct 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment Course A: E-field Modeling | Experimental | Device: iTBSYour 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. |
| Treatment Course B: Beam F3 | Active comparator | Device: iTBSThe 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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| iTBSrTMS 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. | Device | Treatment Course A: E-field Modeling, Treatment Course B: Beam F3 |
Primary outcome
Markers of cortical excitation
Time frame: change from pre-intervention to post-intervention (average of 6 weeks)
TMS-EEG markers of increased cortical excitation (GMFA-AUC)
Depression scores
Time frame: changes from baseline to Week 4 follow-up
Hamilton depression rating scale (HDRS-17) scores
1 secondary outcome
Peripheral biomarkers
Time frame: change from Pre- and post-intervention (average of 6 weeks)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Sep 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing iTBS in people with Major Depressive Disorder, run by Centre for Addiction and Mental Health at 2 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 26 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Daphne Voineskos, MD (416-535-8501 ext. 30176, daphne.voineskos@camh.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Markers of cortical excitation (time frame: change from pre-intervention to post-intervention (average of 6 weeks)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Sep 2023.