Comparing Uni- and Bi-lateral TBS in Major Depression

NCT04142996 | Recruiting

• 1 other identifier: 2019017
• Study Type: interventional
• Target: 256
• Locations: 1 country
• Sites: 1

Brief Summary

Repetitive transcranial magnetic stimulation (rTMS) is a Health Canada approved treatment for major depression. Theta burst stimulation (TBS) is a very promising new treatment for major depression that allows a 15-fold reduction in duration of daily sessions. However, no large scale naturalistic study has assessed the superiority of bilateral TBS in comparison with unilateral left TBS. In fact, no TBS study thus far has included both unipolar and bipolar depression, or other psychiatric comorbidities such as anxiety. Maintenance has yet to be studied with TBS, along with an effective maintenance protocol to prevent relapse. Our study aims to explore and address these gaps.

Conditions

Major Depressive Episode

Outcome Measures

Primary Outcomes (4)

• Response - Treatment Phase (Hamilton Rating Scale for Depression-17 score)

  Response to treatment will be defined as a \> 50% reduction in pre-treatment symptoms severity as measured by the mean Hamilton Rating Scale for Depression-17 score. The minimum value is 0 and the maximum value is 53. A higher score indicates a negative outcome.

  Week 6

• Remission - Treatment Phase (Hamilton Rating Scale for Depression-17 Score)

  Remission will be defined as a Hamilton Rating Scale for Depression-17 score ≤ 8 The minimum value is 0 and the maximum value is 53. A higher score indicates a negative outcome.

  End of treatment phase (week 4 or 6)

• Response - Maintenance Phase (Hamilton Rating Scale for Depression-17 score)

  Response to treatment will be defined as a \> 50% reduction in pre-treatment symptoms severity as measured by the mean Hamilton Rating Scale for Depression-17 score. The minimum value is 0 and the maximum value is 53. A higher score indicates a negative outcome

  6 months

• Remission - Maintenance Phase (Hamilton Rating Scale for Depression-17 Score)

  Remission will be defined as a Hamilton Rating Scale for Depression-17 score ≤ 8 The minimum value is 0 and the maximum value is 53. A higher score indicates a negative outcome.

  6 months

Secondary Outcomes (4)

• Response - Treatment Phase (Quick Inventory of Depression Symptomology-Self Report)

  Week 6

• Remission - Treatment Phase (Quick Inventory of Depression Symptomology-Self Report)

  End of treatment phase (week 4 or 6)

• Response - Maintenance Phase (Quick Inventory of Depression Symptomology-Self Report)

  6 months

• Remission - Maintenance Phase Quick Inventory of Depression Symptomology-Self Report)

  6 months

Other Outcomes (5)

• Cortical Activity - Treatment Phase

  Week 6

• Cortical Activity - Maintenance Phase

  6 months

• Resting State Connectivity

  6 months

Study Arms (3)

Unilateral TBS

ACTIVE COMPARATOR

Intermittent Theta Burst Stimulation (iTBS) will be applied to the left DLPFC. Realistic sham continuous TBS (cTBS-sham) will be applied to the right DLPFC. Participants will receive daily sessions (Mon-Fri) for 4 to 6 weeks (stop at 4 weeks if remission is achieved).

Device: Theta burst stimulation

Bilateral TBS

ACTIVE COMPARATOR

Intermittent Theta Burst Stimulation (iTBS) will be applied to the left DLPFC and continuous TBS (cTBS) will be applied to the right DLPFC. Participants will receive daily sessions (Mon-Fri) for 4 to 6 weeks (stop at 4 weeks if remission is achieved).

Device: Theta burst stimulation

Maintenance Phase: Flexible

ACTIVE COMPARATOR

The flexible maintenance protocol will be based on symptom emergence. Participants will receive a fixed TBS (2x/week) schedule for the first month. For the following months (2-6), they will come in for an assessment (HRSD-17) to determine how many TBS sessions (0, 1, or 2) they receive on a flexible basis.

Device: Theta burst stimulation

Interventions

Theta burst stimulation DEVICE

Cool B70 coil (left DLPFC) and Cool B65 active/placebo coil (right DLPFC), with X100 MagPro rTMS Device (Magventure A/S, Farum, Denmark)

Bilateral TBS; Maintenance Phase: Flexible; Unilateral TBS

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• voluntary and competent to consent to study,
• female or male aged 18 years old or older,
• can speak and read English and/or French
• primary and/or predominant diagnosis of major depressive episode without psychotic features in the current depressive episode (confirmed by a Mini-International Neuropsychiatric Interview),
• depressive symptoms have not improved after ≥ 1 adequate dose of antidepressant trial in the current depressive episode,
• moderate symptoms in the current depressive episode as indexed by a score of at least 15 at the 17-item Hamilton Rating Scale for Depression (HRSD-17),
• have been referred to rTMS treatment by their treating physician, and took a free and informed decision to follow this treatment,
• are able to adhere to treatment schedule,
• have received a stable psychiatric medication (including prescribed cannabis) or psychotherapy regimen for at least four weeks prior to entering the trial,
• have an education-adjusted score of ≥ 24 at the Mini-Mental State Evaluation (MMSE) if are aged ≥ 65.

You may not qualify if:

• current use of illegal substances or recreational cannabis
• have a concomitant major unstable medical or neurologic illness (e.g. uncontrolled diabetes or renal dysfunction),
• organic cause to the depressive symptoms (e.g. thyroid dysfunctions), determined by the referring physician
• acute suicidality or threat to life from self-neglect,
• are pregnant or breastfeeding, or thinking of becoming pregnant during course of treatment,
• have a specific contraindication for TMS (e.g., personal history of epilepsy or seizure, metallic head implant, pacemaker),
• unwilling to maintain current antidepressant regimen,
• are taking more than 1 mg of lorazepam or equivalent,
• any other condition that, in the opinion of the investigators, would adversely affect the participant's ability to complete the study,
• have failed a course of electroconvulsive therapy (ECT) within the current depressive episode due to the lower likelihood of response to rTMS.If they have had failed ECT in the past, this does not exclude them

Sponsors & Collaborators

• The Royal Ottawa Mental Health Centre: lead

Study Sites (1)

The Royal Ottawa Mental Health Centre

Ottawa, Ontario, K1Z 7K4, Canada

RECRUITING

Related Publications (1)

• Watson M, Chaves AR, Gebara A, Desforges M, Broomfield A, Landry N, Lemoyne A, Shim S, Drodge J, Cuda J, Kiaee N, Nasr Y, Carleton C, Daskalakis ZJ, Taylor R, Tuominen L, Brender R, Antochi R, McMurray L, Tremblay S. A naturalistic study comparing the efficacy of unilateral and bilateral sequential theta burst stimulation in treating major depression - the U-B-D study protocol. BMC Psychiatry. 2023 Oct 10;23(1):739. doi: 10.1186/s12888-023-05243-4.

  PMID: 37817124 DERIVED

Study Officials

• Sara Tremblay, PhD

  The Royal Ottawa Mental Health Centre

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Stacey Shim, MSc

CONTACT

613-722-6521; stacey.shim@theroyal.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Both participants and research team members conducting the interviews and the TBS treatment will be blinded to the TBS treatment condition. In the unilateral arm, the right-sided stimulation will be applied with the placebo side of the coil. In the bilateral arm, the right-sided stimulation will be applied with the active side of the coil. As such, all participants will receive a total of 4 minutes of daily TBS. The master randomization list was created by a scientist of the research centre that is not involved in the research project. The patient's study identification (ID) code is entered into the device and a software-controlled switch then automatically selects the active or the sham coil for stimulation. The electronic positioning sensor built in the coil for monitoring the coil orientation checks against the entered patient's study ID and will enable the device and start the treatment procedure only if the coil orientation is matching the patient's study ID value.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 15, 2019
• First Posted: October 29, 2019
• Study Start: December 12, 2019
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: December 4, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will share
• Time Frame: De-identified data may become available (upon request) when the study is completed and published (anticipated time frame: the year of 2026)
• Access Criteria: De-identified data will be accessible only through the permission of the lead research scientist. All requests must be made and accepted by her.

Locations

CA (1)