DepressionLeRNITNCT04999553
Left vs. Right Non-Inferiority Trial
A study testing Repetitive Transcranial Magnetic Stimulation, Intermittent Theta Burst Stimulation (iTBS) and Low Frequency Right (LFR) in people with Depression and Major Depressive Disorder, run by University of British Columbia at 2 sites in Canada.
Trial summary
The aim of this study is to test the hypothesis that low-frequency rTMS (LFR) works as well as the established intermittent thetaburst rTMS (iTBS) treatment for treatment resistant depression (TRD). Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Depression, Major Depressive Disorder, Major Depressive Episode
- What is being tested?
- Repetitive Transcranial Magnetic Stimulation, Intermittent Theta Burst Stimulation (iTBS) and Low Frequency Right (LFR)
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 480 participants
- Where
- 2 sitesCanada
- Study dates
- 8 Nov 2021to 1 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 female or male;
- are outpatients;
- are voluntary and competent to consent to treatment;
- have a DSM 5 diagnosis of MDD,55 single or recurrent confirmed by Mini-International Neuropsychiatric Interview (MINI) version 7.0;
- are 18yo to 65yo;
- have failed to achieve 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 two separate trials of antidepressants at less than the minimum adequate dose and/or duration (ATHF 1 or 2);
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- have a score ≥ 18 on the Hamilton Depression Rating Scale (HDRS-17 item);
- have had no increase or initiation of any psychotropic medication in the 4 weeks prior to screening;
- are able to adhere to the treatment schedule;
- pass the TMS and MRI adult safety screening questionnaires.
Who cannot join
- have a history of substance use within the last 3 months;
- have a concomitant major unstable medical illness;
- have active suicidal intent;
- are pregnant;
- have a lifetime (MINI) diagnosis of any psychotic or bipolar disorder;
- have a MINI anxiety disorder or personality disorder assessed by a study investigator to be primary and causing greater impairment than MDD;
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- have failed a course of ECT in the current episode;
- have any significant neurological disorder, any history of seizure (except those therapeutically induced by ECT), significant head trauma with loss of consciousness for > 5 min;
- have any intracranial implant (e.g., aneurysm clips) or any other metal object within or near the head, excluding the mouth, that cannot be safely removed;
- are participating in psychotherapy, must have been in stable treatment for at least 3 months prior to study entry, with no anticipated change in the frequency of therapeutic sessions, or focus of therapeutic sessions over the duration of the study;
- have a clinically significant laboratory abnormality, in the opinion of the one of the principal investigators;
- 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
Centre for Addiction and Mental Health
Toronto, Ontario, M6J 1H4
Stacey Shim, MSc, 416-535-8501 ext. 30210, Stacey.Shim@camh.ca
Daniel Blumberger, MD, MSc
- Recruiting
Non-Invasive Neurostimulation Therapies Centre, University of British Columbia
Vancouver, British Columbia, V6T 2A1
Amanda Ding, 6048221361, ninet.lab@ubc.ca
Fidel Vila-Rodriguez, MD, PhD
About this study
Official title: Left Intermittent Theta Burst Stimulation vs. Right Low Frequency Repetitive Transcranial Magnetic Stimulation Effectiveness in Depression and Suicidal Ideation: A Randomized Non-Inferiority Trial
The aim of this study is to test the hypothesis that low-frequency rTMS (LFR) works as well as the established intermittent thetaburst rTMS (iTBS) treatment for treatment resistant depression (TRD).
Read the detailed description
In this multi-centre, triple-blinded, non-inferiority trial 420 patients with TRD will be recruited at two academic centres (UBC, CAMH). Patients will be randomised to receive either iTBS or LFR for 30 sessions. The primary outcome will be the improvement on a depression scale. Secondary outcome will be improvement of suicidal ideation. A secondary aim is to test the predictive capacity of a novel, easy to implement heart rate based biomarkers (i.e. heart rate variability).
- Being tested
- Repetitive Transcranial Magnetic Stimulation, Intermittent Theta Burst Stimulation (iTBS), Low Frequency Right (LFR)
- Keywords
- rTMS, TMS, Transcranial Magnetic Stimulation, iTBS, Depression, Major Depressive Disorder
- Medical subject headings
- Depression, Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Repetitive Transcranial Magnetic StimulationDevice
rTMS will employ the MagPro X100/R30 stimulator equipped with the cool-B70 as we used a cool-B70 in our past non-inferiority trial. The dose will be a 120% rMT in accordance to our latest trial using iTBS. The target area to stimulate will be the right dorsolateral prefrontal cortex (DLPFC) for LFR and the left DLPFC for iTBS as established in prior clinical trials. The localization of both targets will follow the well-established procedures for either R-DLPFC or L-DLPFC using a heuristic method.
Intermittent Theta Burst Stimulation (iTBS)Device
Intermittent Theta Burst Stimulation (iTBS)
Low Frequency Right (LFR)Device
Low Frequency Right (LFR)
| Study group | Role | What they receive |
|---|---|---|
| Intermittent Theta Burst Stimulation (iTBS) | Active comparator | iTBS to the L-DLPFC Receives: Device: Repetitive Transcranial Magnetic Stimulation; Device: Intermittent Theta Burst Stimulation (iTBS) |
| Low Frequency Right (LFR) | Active comparator | 1Hz stimulation to the R-DLPFC Receives: Device: Repetitive Transcranial Magnetic Stimulation; Device: Low Frequency Right (LFR) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Depression severity
17 item Hamilton Depression Rating Scale (HDRS-17) Change
Measured: 30 days
Secondary outcomes (3)
Suicidal ideation
Columbia Suicide Severity Rating Scale Screen Version (C-SSRS) Change
Measured: 30 days
Anxiety severity
Hamilton Anxiety Rating Scale (HAM-A) Change
Measured: 30 days
Depression severity
Self-rated 16-item Quick Inventory of Depressive Symptoms (QIDS-16) Change
Measured: 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Aug 2021
- Study start8 Nov 2021
- Primary completion1 Jun 2027 (estimated)
- Study completion1 Jul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for DepressionStudies of the same condition, open and under way.
- More trials run by University of British ColumbiaThe sponsor's other registered studies.
- 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
- Model description
- This is a two-arm multicenter parallel, clinician-blinded randomized non-inferiority trial
- Masking
- Double blind
- Who is masked
- Investigator, Outcomes assessor
- Enrolment
- 480 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of British Columbia
- Sponsor type
- University, hospital or other
- Collaborators
- Centre for Addiction and Mental Health
- Responsible party
- Principal investigator, Fidel Vila-Rodriguez, MD, PhD, FRCPC, DFAPA, University of British Columbia
- Investigators
- Fidel Vila-Rodriguez, MD, PhD, Principal investigator, University of British Columbia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04999553
- Sponsor's protocol ID
- H18-00583
- Acronym
- LeRNIT
- Status last verified
- Aug 2026
- First submitted
- 2 Aug 2021
- Last updated
- 25 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Left Intermittent Theta Burst Stimulation vs. Right Low Frequency Repetitive Transcranial Magnetic Stimulation Effectiveness in Depression and Suicidal Ideation: A Randomized Non-Inferiority Trial
- ClinicalTrials.gov ID
- NCT04999553
- Acronym / sponsor ID
- LeRNIT / H18-00583
- Keywords
- rTMS, TMS, Transcranial Magnetic Stimulation, iTBS, Depression, Major Depressive Disorder
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 480 participants (estimated)
- Lead sponsor
- University of British ColumbiaUniversity, hospital or other
- Collaborators
- Centre for Addiction and Mental Health
- Study start
- 8 Nov 2021 (actual)
- Primary completion
- 1 Jun 2027 (estimated)
- Study completion
- 1 Jul 2027 (estimated)
- First posted
- 11 Aug 2021 (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 aim of this study is to test the hypothesis that low-frequency rTMS (LFR) works as well as the established intermittent thetaburst rTMS (iTBS) treatment for treatment resistant depression (TRD).
Detailed description
In this multi-centre, triple-blinded, non-inferiority trial 420 patients with TRD will be recruited at two academic centres (UBC, CAMH). Patients will be randomised to receive either iTBS or LFR for 30 sessions. The primary outcome will be the improvement on a depression scale. Secondary outcome will be improvement of suicidal ideation. A secondary aim is to test the predictive capacity of a novel, easy to implement heart rate based biomarkers (i.e. heart rate variability).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- This is a two-arm multicenter parallel, clinician-blinded randomized non-inferiority trial
| Arm | Type | Receives |
|---|---|---|
| Intermittent Theta Burst Stimulation (iTBS) | Active comparator | Device: Repetitive Transcranial Magnetic Stimulation, Device: Intermittent Theta Burst Stimulation (iTBS)iTBS to the L-DLPFC |
| Low Frequency Right (LFR) | Active comparator | Device: Repetitive Transcranial Magnetic Stimulation, Device: Low Frequency Right (LFR)1Hz stimulation to the R-DLPFC |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- are female or male;
- are outpatients;
- are voluntary and competent to consent to treatment;
- have a DSM 5 diagnosis of MDD,55 single or recurrent confirmed by Mini-International Neuropsychiatric Interview (MINI) version 7.0;
- are 18yo to 65yo;
Key exclusion criteria (12 listed)
- have a history of substance use within the last 3 months;
- have a concomitant major unstable medical illness;
- have active suicidal intent;
- are pregnant;
- have a lifetime (MINI) diagnosis of any psychotic or bipolar disorder;
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 |
|---|---|---|
| Repetitive Transcranial Magnetic StimulationrTMS will employ the MagPro X100/R30 stimulator equipped with the cool-B70 as we used a cool-B70 in our past non-inferiority trial. The dose will be a 120% rMT in accordance to our latest trial using iTBS. The target area to stimulate will be the right dorsolateral prefrontal cortex (DLPFC) for LFR and the left DLPFC for iTBS as established in prior clinical trials. The localization of both targets will follow the well-established procedures for either R-DLPFC or L-DLPFC using a heuristic method. | Device | Intermittent Theta Burst Stimulation (iTBS), Low Frequency Right (LFR) |
| Intermittent Theta Burst Stimulation (iTBS)Intermittent Theta Burst Stimulation (iTBS) | Device | Intermittent Theta Burst Stimulation (iTBS) |
| Low Frequency Right (LFR)Low Frequency Right (LFR) | Device | Low Frequency Right (LFR) |
Primary outcome
Depression severity
Time frame: 30 days
17 item Hamilton Depression Rating Scale (HDRS-17) Change
3 secondary outcomes
Suicidal ideation
Time frame: 30 days
Anxiety severity
Time frame: 30 days
Depression severity
Time frame: 30 days
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 25 Aug 2026.
- Individual participant dataSharing planned: No
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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.
Fidel Vila-Rodriguez, MD, PhD principal investigator
University of British Columbia
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Repetitive Transcranial Magnetic Stimulation, Intermittent Theta Burst Stimulation (iTBS) and Low Frequency Right (LFR) in people with Depression and Major Depressive Disorder, run by University of British Columbia 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 10 inclusion and 12 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 25 Aug 2026. 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 Amanda Ding (604-827-1361, ninet.lab@ubc.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Depression severity (time frame: 30 days). 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 25 Aug 2026.