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Accelerated High-dose Sequential Bilateral Theta Burst Stimulation for Treatment Resistant Depression

Primary Purpose

Treatment Resistant Depression

Status
Not yet recruiting
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Sequential bilateral theta burst stimulation
Sponsored by
University of Calgary
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Treatment Resistant Depression

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Diagnosis of MDD (DSM-V) Adults in the age range of 18 - 65 Both sex HAMD-17 score of ≥20 TRD - failure to two antidepressant trial Stage II (Thase and Rush classification) Exclusion Criteria: Post traumatic stress disorder, Obsessive compulsive disorder, Psychosis Bipolar disorder, substance abuse disorder, autistic spectrum disorder, active suicidal behavior Epilepsy Dementia, Movement disorders severe head injury Brain metallic implants, cardiac pacemakers Pregnancy . Non-response to prior rTMS, Electroconvulsive treatment, Vagal nerve or Deep brain stimulation or a history of psychosurgery. Borderline personality disorder, Schizotypal, schizoid & paranoid personality disorder Current treatment with anticonvulsants or benzodiazepines

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Sham Comparator

    Arm Label

    Active stimulation

    Sham stimulation

    Arm Description

    Bilateral real TBS

    Bilateral Sham stimulation

    Outcomes

    Primary Outcome Measures

    Montgomery Asberg Depression Rating Scale (MADRS)
    Mean change in Montgomery Asberg Depression Rating Scale (MADRS) scores (0-60) from baseline to week 4 post treatment. Higher scores mean worse outcome.

    Secondary Outcome Measures

    Hamilton Depression Rating Scale-17(HDRS-17)
    Mean change in Hamilton Depression Rating Scale-17(HDRS-17) scores (0-52) from baseline to week 4 post treatment. Higher scores mean worse outcome
    Quick Inventory of Depressive Symptomatology- Self Report (QIDS-SR)
    Mean change in Quick Inventory of Depressive Symptomatology- Self Report (QIDS-SR) scores (0-27) from baseline to week 4 post treatment. Higher scores mean worse outcome.
    Columbia scale of suicidal behavior (CSS)
    Mean change in Columbia scale of suicidal behavior (CSS) scores (2-25) from baseline to week 4 post treatment. Higher scores mean worse outcome.
    World Health Organization Quality of Life ( WHOQOL) BREF
    Mean change in Quality of Life- ( WHOQOL) BREF - scores ( 0-100) from baseline to week 4 post treatment. Higher scores mean better outcome.
    Clinical Global Impression Scale (CGI)
    Mean change from Clinical Global Impression Scale (CGI) ( 1-7) baseline to week 4 post treatment. Higher scores mean worse outcome
    Categorical outcomes
    Response (a reduction ≥ 50% in MADRS from the baseline to 4 weekend point) and remission (MADRS score ≤ 10) rates for each group

    Full Information

    First Posted
    January 5, 2023
    Last Updated
    March 30, 2023
    Sponsor
    University of Calgary
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05811104
    Brief Title
    Accelerated High-dose Sequential Bilateral Theta Burst Stimulation for Treatment Resistant Depression
    Official Title
    Accelerated High-dose Sequential Bilateral Theta Burst Stimulation for Treatment Resistant Depression: A Randomized Double-Blind Sham-controlled Pilot Study
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    March 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    May 20, 2023 (Anticipated)
    Primary Completion Date
    May 20, 2025 (Anticipated)
    Study Completion Date
    June 30, 2025 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    University of Calgary

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    Repetitive transcranial magnetic stimulation (rTMS) and Theta burst stimulation (TBS) are approved by the US. Food and Drug administration (FDA) for the treatment of refractory major depression. TBS is more efficient than rTMS as it requires shorter stimulation time.Studies suggest that the efficacy of TBS could be enhanced and expedited by accelerated protocols (more than once daily sessions) with higher doses of stimulation (>600 TBS pulses up to 3600 pulses per session) and shorter duration of treatment (4-10days). The main objective of this study is to determine the clinical efficacy and safety of accelerated high dose bilateral TBS treatment for patients with treatment resistant depression in comparison to sham stimulation using a randomized double blind clinical trial design.
    Detailed Description
    Major depressive disorder (MDD) accounts for the highest global burden of all mental health disorders, and approximately 50% of depressed patients meet criteria for treatment resistant of depression. Stimulation based therapies have recently become a promising alternative for patients with treatment resistant depression. Repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex (DLPFC) is approved by the US. Food and Drug administration (FDA) and has been recommended as a viable treatment option for major depression. Recently, a newer form of rTMS called Theta burst stimulation (TBS) is approved by FDA as it has shown comparable clinical efficacy and safety to rTMS in the treatment of depression. TBS is more efficient than rTMS as it requires shorter stimulation time of ≤ 6min compared to 20-40 min required in conventional rTMS protocol and produces equivalent antidepressant responses. Studies suggest that the efficacy of TBS could be enhanced and expedited by accelerated protocols (more than once daily sessions ranging from 2-10 sessions/day) higher doses of stimulation (>600 TBS pulses up to 3600 pulses per session) with shorter duration of treatment (4-10days). Recently, an accelerated Stanford Neuromodulation Therapy protocol (10 sessions of iTBS a day for 5 days) with high dose stimulation (90,000 pulses in total) was found to be more effective than sham for severe TRD. This protocol yielded robust results with 69.2% response rates compared to 13% in sham during the 4-week outcome period . The main goal of this project is to determine the clinical efficacy and safety of accelerated high dose bilateral TBS treatment for TRD in comparison to sham stimulation using a randomized double blind clinical trial design. The second objective is to examine the durability of antidepressant effect of this treatment protocol. Our initial open label study of accelerated high dose bilateral TBS demonstrated efficacy in a small cohort of participants with TRD. This proposed study builds on our initial findings whether the antidepressant efficacy of accelerated high dose bilateral TBS would be significantly greater than an identical schedule of sham stimulation. This pilot study will help to examine the feasibility, acceptability, and tolerability of treatment protocol, and estimate the sample size for the next pivotal trial. Hypotheses: Accounting this is a pilot study using small sample size without power size calculations, it is not designed for hypothesis testing. However, it is predicted that the accelerated bilateral TBS would be clinically effective and safe in the treatment of patients with TRD compared to sham stimulation. Additionally, it is anticipated that the antidepressant effects of this treatment may be durable.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Treatment Resistant Depression

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Not Applicable
    Interventional Study Model
    Parallel Assignment
    Model Description
    This will be a randomized, sham-controlled, double-blind single centre study using a 1:1 ratio parallel design. We aim to recruit 40 participants (active=20; sham =20) for this pilot study
    Masking
    ParticipantInvestigatorOutcomes Assessor
    Masking Description
    Participants, clinical assessors and treatment providers will be blinded to treatment assignments.
    Allocation
    Randomized
    Enrollment
    40 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Active stimulation
    Arm Type
    Experimental
    Arm Description
    Bilateral real TBS
    Arm Title
    Sham stimulation
    Arm Type
    Sham Comparator
    Arm Description
    Bilateral Sham stimulation
    Intervention Type
    Device
    Intervention Name(s)
    Sequential bilateral theta burst stimulation
    Intervention Description
    Three sessions of active or sham bilateral TBS will be delivered daily for 10 days in 2 weeks (no session on weekend) with a total of 30 sessions for each patient. Daily low intensity (90% resting motor threshold) bilateral sequential continousTBS ( cTBI) will be applied first on the right DLPFC (1800 pulses) and then intermittent TBS (iTBS)on the left DLPFC (1800 pulses) with an intersession interval of 60 minutes. We will adopt 1800 pulse per session based on the previous studies. Patients will receive a stimulation of 3600 pulses a session, 10,800 pulses a day and 108,000 pulses in total. After the study, sham group will receive active stimulation following the same protocol
    Primary Outcome Measure Information:
    Title
    Montgomery Asberg Depression Rating Scale (MADRS)
    Description
    Mean change in Montgomery Asberg Depression Rating Scale (MADRS) scores (0-60) from baseline to week 4 post treatment. Higher scores mean worse outcome.
    Time Frame
    Baseline to week 4 post treatment
    Secondary Outcome Measure Information:
    Title
    Hamilton Depression Rating Scale-17(HDRS-17)
    Description
    Mean change in Hamilton Depression Rating Scale-17(HDRS-17) scores (0-52) from baseline to week 4 post treatment. Higher scores mean worse outcome
    Time Frame
    Baseline to week 4 post treatment
    Title
    Quick Inventory of Depressive Symptomatology- Self Report (QIDS-SR)
    Description
    Mean change in Quick Inventory of Depressive Symptomatology- Self Report (QIDS-SR) scores (0-27) from baseline to week 4 post treatment. Higher scores mean worse outcome.
    Time Frame
    Baseline to week 4 post treatment
    Title
    Columbia scale of suicidal behavior (CSS)
    Description
    Mean change in Columbia scale of suicidal behavior (CSS) scores (2-25) from baseline to week 4 post treatment. Higher scores mean worse outcome.
    Time Frame
    Baseline to week 4 post treatment
    Title
    World Health Organization Quality of Life ( WHOQOL) BREF
    Description
    Mean change in Quality of Life- ( WHOQOL) BREF - scores ( 0-100) from baseline to week 4 post treatment. Higher scores mean better outcome.
    Time Frame
    Baseline to week 4 post treatment
    Title
    Clinical Global Impression Scale (CGI)
    Description
    Mean change from Clinical Global Impression Scale (CGI) ( 1-7) baseline to week 4 post treatment. Higher scores mean worse outcome
    Time Frame
    Baseline to week 4 post treatment
    Title
    Categorical outcomes
    Description
    Response (a reduction ≥ 50% in MADRS from the baseline to 4 weekend point) and remission (MADRS score ≤ 10) rates for each group
    Time Frame
    At 4 week post treatment

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    65 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Diagnosis of MDD (DSM-V) Adults in the age range of 18 - 65 Both sex HAMD-17 score of ≥20 TRD - failure to two antidepressant trial Stage II (Thase and Rush classification) Exclusion Criteria: Post traumatic stress disorder, Obsessive compulsive disorder, Psychosis Bipolar disorder, substance abuse disorder, autistic spectrum disorder, active suicidal behavior Epilepsy Dementia, Movement disorders severe head injury Brain metallic implants, cardiac pacemakers Pregnancy . Non-response to prior rTMS, Electroconvulsive treatment, Vagal nerve or Deep brain stimulation or a history of psychosurgery. Borderline personality disorder, Schizotypal, schizoid & paranoid personality disorder Current treatment with anticonvulsants or benzodiazepines
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Rajamannar Ramasubbu, MD
    Phone
    403-471-4794
    Email
    rramasub@ucalgary.ca
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Rajamannar Ramasubbu, MD
    Organizational Affiliation
    University of Calgary
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    No
    Citations:
    PubMed Identifier
    18704101
    Citation
    Lisanby SH, Husain MM, Rosenquist PB, Maixner D, Gutierrez R, Krystal A, Gilmer W, Marangell LB, Aaronson S, Daskalakis ZJ, Canterbury R, Richelson E, Sackeim HA, George MS. Daily left prefrontal repetitive transcranial magnetic stimulation in the acute treatment of major depression: clinical predictors of outcome in a multisite, randomized controlled clinical trial. Neuropsychopharmacology. 2009 Jan;34(2):522-34. doi: 10.1038/npp.2008.118. Epub 2008 Aug 13.
    Results Reference
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    PubMed Identifier
    24351501
    Citation
    Thomas L, Kessler D, Campbell J, Morrison J, Peters TJ, Williams C, Lewis G, Wiles N. Prevalence of treatment-resistant depression in primary care: cross-sectional data. Br J Gen Pract. 2013 Dec;63(617):e852-8. doi: 10.3399/bjgp13X675430.
    Results Reference
    result
    PubMed Identifier
    25655160
    Citation
    Levkovitz Y, Isserles M, Padberg F, Lisanby SH, Bystritsky A, Xia G, Tendler A, Daskalakis ZJ, Winston JL, Dannon P, Hafez HM, Reti IM, Morales OG, Schlaepfer TE, Hollander E, Berman JA, Husain MM, Sofer U, Stein A, Adler S, Deutsch L, Deutsch F, Roth Y, George MS, Zangen A. Efficacy and safety of deep transcranial magnetic stimulation for major depression: a prospective multicenter randomized controlled trial. World Psychiatry. 2015 Feb;14(1):64-73. doi: 10.1002/wps.20199.
    Results Reference
    result
    PubMed Identifier
    29726344
    Citation
    Blumberger DM, Vila-Rodriguez F, Thorpe KE, Feffer K, Noda Y, Giacobbe P, Knyahnytska Y, Kennedy SH, Lam RW, Daskalakis ZJ, Downar J. Effectiveness of theta burst versus high-frequency repetitive transcranial magnetic stimulation in patients with depression (THREE-D): a randomised non-inferiority trial. Lancet. 2018 Apr 28;391(10131):1683-1692. doi: 10.1016/S0140-6736(18)30295-2. Epub 2018 Apr 26. Erratum In: Lancet. 2018 Jun 23;391(10139):e24.
    Results Reference
    result
    PubMed Identifier
    34711062
    Citation
    Cole EJ, Phillips AL, Bentzley BS, Stimpson KH, Nejad R, Barmak F, Veerapal C, Khan N, Cherian K, Felber E, Brown R, Choi E, King S, Pankow H, Bishop JH, Azeez A, Coetzee J, Rapier R, Odenwald N, Carreon D, Hawkins J, Chang M, Keller J, Raj K, DeBattista C, Jo B, Espil FM, Schatzberg AF, Sudheimer KD, Williams NR. Stanford Neuromodulation Therapy (SNT): A Double-Blind Randomized Controlled Trial. Am J Psychiatry. 2022 Feb;179(2):132-141. doi: 10.1176/appi.ajp.2021.20101429. Epub 2021 Oct 29.
    Results Reference
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    PubMed Identifier
    34050123
    Citation
    Voigt JD, Leuchter AF, Carpenter LL. Theta burst stimulation for the acute treatment of major depressive disorder: A systematic review and meta-analysis. Transl Psychiatry. 2021 May 28;11(1):330. doi: 10.1038/s41398-021-01441-4.
    Results Reference
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    Accelerated High-dose Sequential Bilateral Theta Burst Stimulation for Treatment Resistant Depression

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