Comparing two types of brain stimulation for treatment-resistant depression

Left Intermittent Theta Burst Stimulation vs. Right Low Frequency Repetitive Transcranial Magnetic Stimulation Effectiveness in Depression and Suicidal Ideation: A Randomized Non-Inferiority Trial

This study is testing if a new type of brain stimulation can help people with treatment-resistant depression just as well as a current method they already use.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 420 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: University of British Columbia (Academic / other)
• Locations: 2 sites (Vancouver, British Columbia and 1 other locations)
• Trial ID: NCT04999553 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to determine if low-frequency repetitive Transcranial Magnetic Stimulation (LFR) is as effective as the established intermittent theta burst stimulation (iTBS) for patients with treatment-resistant depression (TRD). A total of 420 patients will be recruited from two academic centers and randomly assigned to receive either treatment for 30 sessions. The primary outcome will be measured through improvements on a depression scale, while secondary outcomes will assess changes in suicidal ideation and the predictive capacity of heart rate variability as a biomarker. The study employs a multi-centre, triple-blinded, non-inferiority design to ensure robust results.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 65 with a diagnosis of major depressive disorder who have not responded to previous antidepressant treatments.

Not a fit: Patients with a recent history of substance use or those who have not adhered to treatment schedules may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide an effective alternative treatment for patients with treatment-resistant depression.

How similar studies have performed: Previous studies have shown promising results with similar approaches using rTMS for depression, indicating potential for success in this trial.

Eligibility criteria

Inclusion Criteria:

1. are female or male;
2. are outpatients;
3. are voluntary and competent to consent to treatment;
4. have a DSM 5 diagnosis of MDD,55 single or recurrent confirmed by Mini-International Neuropsychiatric Interview (MINI) version 7.0;
5. are 18yo to 65yo;
6. 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);
7. have a score ≥ 18 on the Hamilton Depression Rating Scale (HDRS-17 item);
8. have had no increase or initiation of any psychotropic medication in the 4 weeks prior to screening;
9. are able to adhere to the treatment schedule;
10. pass the TMS and MRI adult safety screening questionnaires.

Exclusion Criteria:

1. have a history of substance use within the last 3 months;
2. have a concomitant major unstable medical illness;
3. have active suicidal intent;
4. are pregnant;
5. have a lifetime (MINI) diagnosis of any psychotic or bipolar disorder;
6. have a MINI anxiety disorder or personality disorder assessed by a study investigator to be primary and causing greater impairment than MDD;
7. have failed a course of ECT in the current episode;
8. 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;
9. 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;
10. 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;
11. have a clinically significant laboratory abnormality, in the opinion of the one of the principal investigators;
12. have a non-correctable clinically significant sensory impairment (i.e., cannot hear well enough to cooperate with interview);

Where this trial is running

Vancouver, British Columbia and 1 other locations

• Non-Invasive Neurostimulation Therapies Centre, University of British Columbia — Vancouver, British Columbia, Canada (Recruiting)
• Centre for Addiction and Mental Health — Toronto, Ontario, Canada (Recruiting)

Study contacts

• Principal investigator: Fidel Vila-Rodriguez, MD, PhD — University of British Columbia
• Study coordinator: Afifa Humaira, BSc

Conditions Depression; Major Depressive Disorder; Major Depressive Episode; rTMS; TMS; Transcranial Magnetic Stimulation; iTBS