Left vs. Right Non-Inferiority Trial

Depression Clinical Trial

— LeRNIT  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04999553
• Other study ID #: H18-00583
• Status: Recruiting
• Phase: N/A
• Start date: November 8, 2021
• Est. completion date: February 1, 2026

Study information

• Verified date: November 2021
• Source: University of British Columbia
• Contact: Afifa Humaira, BSc
• Phone: 604-827-1361
• Email: afifa.humaira[@]ubc.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical 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).

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 420
• Est. completion date: February 1, 2026
• Est. primary completion date: February 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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);

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Major Depressive Disorder
• Major Depressive Episode

Intervention

Device:
• Repetitive Transcranial Magnetic Stimulation
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)
Intermittent Theta Burst Stimulation (iTBS)
• Low Frequency Right (LFR)
Low Frequency Right (LFR)

Locations

Country	Name	City	State
Canada	Centre for Addiction and Mental Health	Toronto	Ontario
Canada	Non-Invasive Neurostimulation Therapies Centre, University of British Columbia	Vancouver	British Columbia

Sponsors (2)

Lead Sponsor	Collaborator
University of British Columbia	Centre for Addiction and Mental Health

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Depression severity	17 item Hamilton Depression Rating Scale (HDRS-17) Change	30 days
Secondary	Suicidal ideation	Columbia Suicide Severity Rating Scale Screen Version (C-SSRS) Change	30 days
Secondary	Anxiety severity	Hamilton Anxiety Rating Scale (HAM-A) Change	30 days
Secondary	Depression severity	Self-rated 16-item Quick Inventory of Depressive Symptoms (QIDS-16) Change	30 days