Left vs. Right Non-Inferiority Trial (LeRNIT)

November 8, 2021 updated by: Fidel Vila-Rodriguez, University of British Columbia

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).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

420

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Canada
    • British Columbia
      • Vancouver, British Columbia, Canada, V6T 2A1
        • Recruiting
        • Non-Invasive Neurostimulation Therapies Centre, University of British Columbia
        • Principal Investigator:
          • Fidel Vila-Rodriguez, MD, PhD
        • Contact:
    • Ontario
      • Toronto, Ontario, Canada, M6J 1H4
        • Recruiting
        • Centre for Addiction and Mental Health
        • Contact:
        • Principal Investigator:
          • Daniel Blumberger, MD, MSc

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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);

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Intermittent Theta Burst Stimulation (iTBS)
iTBS to the L-DLPFC
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.
Device: Intermittent Theta Burst Stimulation (iTBS)
Intermittent Theta Burst Stimulation (iTBS)
Active Comparator: Low Frequency Right (LFR)
1Hz stimulation to the R-DLPFC
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.
Device: Low Frequency Right (LFR)
Low Frequency Right (LFR)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Depression severity
Time Frame: 30 days
17 item Hamilton Depression Rating Scale (HDRS-17) Change
30 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Suicidal ideation
Time Frame: 30 days
Columbia Suicide Severity Rating Scale Screen Version (C-SSRS) Change
30 days
Anxiety severity
Time Frame: 30 days
Hamilton Anxiety Rating Scale (HAM-A) Change
30 days
Depression severity
Time Frame: 30 days
Self-rated 16-item Quick Inventory of Depressive Symptoms (QIDS-16) Change
30 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of British Columbia

Collaborators

Centre for Addiction and Mental Health

Investigators

  • Principal Investigator: Fidel Vila-Rodriguez, MD, PhD, University of British Columbia

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 8, 2021

Primary Completion (Anticipated)

February 1, 2026

Study Completion (Anticipated)

February 1, 2026

Study Registration Dates

First Submitted

August 2, 2021

First Submitted That Met QC Criteria

August 7, 2021

First Posted (Actual)

August 11, 2021

Study Record Updates

Last Update Posted (Actual)

November 10, 2021

Last Update Submitted That Met QC Criteria

November 8, 2021

Last Verified

November 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • H18-00583

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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