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

NCT05811104 | Unknown

• 1 other identifier: 10021798
• Study Type: interventional
• Target: 40
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Treatment Resistant Depression

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline to week 4 post treatment

Secondary Outcomes (6)

• Hamilton Depression Rating Scale-17(HDRS-17)

  Baseline to week 4 post treatment

• Quick Inventory of Depressive Symptomatology- Self Report (QIDS-SR)

  Baseline to week 4 post treatment

• Columbia scale of suicidal behavior (CSS)

  Baseline to week 4 post treatment

• World Health Organization Quality of Life ( WHOQOL) BREF

  Baseline to week 4 post treatment

• Clinical Global Impression Scale (CGI)

  Baseline to week 4 post treatment

Study Arms (2)

Active stimulation

EXPERIMENTAL

Bilateral real TBS

Device: Sequential bilateral theta burst stimulation

Sham stimulation

SHAM COMPARATOR

Bilateral Sham stimulation

Device: Sequential bilateral theta burst stimulation

Interventions

Sequential bilateral theta burst stimulation DEVICE

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

Active stimulation; Sham stimulation

Eligibility Criteria

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

You may qualify if:

• 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)

You may not qualify if:

• 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,

Sponsors & Collaborators

• University of Calgary: lead

Related Publications (6)

• 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.

  PMID: 18704101 BACKGROUND

• 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.

  PMID: 24351501 RESULT

• 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.

  PMID: 25655160 RESULT

• 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.

  PMID: 29726344 RESULT

• 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.

  PMID: 34711062 RESULT

• 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.

  PMID: 34050123 RESULT

MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Study Officials

• Rajamannar Ramasubbu, MD

  University of Calgary

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rajamannar Ramasubbu, MD

CONTACT

403-471-4794; rramasub@ucalgary.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participants, clinical assessors and treatment providers will be blinded to treatment assignments.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor (Clinical)

Model Details: 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

Study Record Dates

• First Submitted: January 5, 2023
• First Posted: April 13, 2023
• Study Start: May 20, 2023
• Primary Completion: May 20, 2025
• Study Completion: June 30, 2025
• Last Updated: April 13, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share