Left vs. Right Non-Inferiority Trial

NCT ID: NCT04999553

Last Updated: 2021-11-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

420 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-11-08

Study Completion Date

2026-02-01

Brief Summary

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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

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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).

Conditions

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Depression Major Depressive Disorder Major Depressive Episode

Keywords

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rTMS TMS Transcranial Magnetic Stimulation iTBS Depression Major Depressive Disorder

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

This is a two-arm multicenter parallel, clinician-blinded randomized non-inferiority trial
Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Investigators Outcome Assessors
Study doctors and raters obtaining outcome measures will be blind to treatment assignment.

Study Groups

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Intermittent Theta Burst Stimulation (iTBS)

iTBS to the L-DLPFC

Group Type ACTIVE_COMPARATOR

Repetitive Transcranial Magnetic Stimulation

Intervention Type DEVICE

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)

Intervention Type DEVICE

Intermittent Theta Burst Stimulation (iTBS)

Low Frequency Right (LFR)

1Hz stimulation to the R-DLPFC

Group Type ACTIVE_COMPARATOR

Repetitive Transcranial Magnetic Stimulation

Intervention Type DEVICE

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.

Low Frequency Right (LFR)

Intervention Type DEVICE

Low Frequency Right (LFR)

Interventions

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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.

Intervention Type DEVICE

Intermittent Theta Burst Stimulation (iTBS)

Intermittent Theta Burst Stimulation (iTBS)

Intervention Type DEVICE

Low Frequency Right (LFR)

Low Frequency Right (LFR)

Intervention Type DEVICE

Eligibility Criteria

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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);
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Centre for Addiction and Mental Health

OTHER

Sponsor Role collaborator

University of British Columbia

OTHER

Sponsor Role lead

Responsible Party

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Fidel Vila-Rodriguez

Principle Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Fidel Vila-Rodriguez, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of British Columbia

Locations

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Non-Invasive Neurostimulation Therapies Centre, University of British Columbia

Vancouver, British Columbia, Canada

Site Status RECRUITING

Centre for Addiction and Mental Health

Toronto, Ontario, Canada

Site Status RECRUITING

Countries

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Canada

Central Contacts

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Afifa Humaira, BSc

Role: CONTACT

Phone: 604-827-1361

Email: [email protected]

Michelle Avina, BSc

Role: CONTACT

Phone: 604-827-1361

Email: [email protected]

Facility Contacts

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Afifa Humaira, BSc

Role: primary

Stacey Shim, MSc

Role: primary

Other Identifiers

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H18-00583

Identifier Type: -

Identifier Source: org_study_id