Accelerated iTBS for Depression and Suicidality

NCT04441008 | Not Yet Recruiting FDA Device

• 1 other identifier: 202002608
• Study Type: interventional
• Target: 50
• Locations: 0 countries
• Sites: N/A

Brief Summary

The overall objective of this current study is to evaluate the feasibility, safety, and tolerability of "high dose" aiTBS in psychiatric inpatient and outpatients with treatment-refractory unipolar, non-psychotic major depressive disorder, using patients receiving ECT as an active comparator. Developing a better understanding of the feasibility and tolerability of adapting this treatment to an acutely ill patient population could lead to huge breakthroughs for clinician decision-making and for the further optimization of brain stimulation depression protocols. The results of this study can help guide future confirmatory efficacy trials of high-dose aiTBS by providing a better understanding of how feasibility, safety and tolerability compare to ECT, as well as unforeseen challenges of its use.

Conditions

Major Depressive Disorder; Suicide

Keywords

transcranial magnetic stimulation, theta burst, accelerated TMS, ECT, electroconvulsive therapy, depression, suicidality

Outcome Measures

Primary Outcomes (1)

• Retention rate at completion of aiTBS vs the ECT group

  The primary tolerability endpoint is the proportion of aiTBS or ECT patients completing the protocol to a degree thought to be satisfactory for achieving the intended antidepressant effect. Completion for aiTBS arm is defined as completion of at least 60% of the treatment protocol (30 of 50 treatments) with treatments on at least 60% of days (3 of 5 days during the week). Completion for ECT arm is defined as completion of at least 2 of 3 ECT treatments during the first week.

  5 days

Study Arms (2)

aiTBS arm

EXPERIMENTAL

aiTBS treatment as lead-in phase to ECT standard of care treatment.

Device: Accelerated Intermittent Theta Burst (aiTBS); Device: Electroconvulsive therapy (ECT)

ECT arm

ACTIVE COMPARATOR

ECT as clinically indicated.

Device: Electroconvulsive therapy (ECT)

Interventions

Accelerated Intermittent Theta Burst (aiTBS) DEVICE

High-dose intermittent theta burst administered at a treatment frequency 10x per day, with each treatment session duration 3x standard TMS (1800 pulses). Delivering 50 sessions in 5 days.

Also known as: SAINT Protocol, accelerated TMS

aiTBS arm

Electroconvulsive therapy (ECT) DEVICE

ECT as per standard clinical care and management.

ECT arm; aiTBS arm

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability to provide informed consent
• Availability for the duration of the study and willingness to comply with all study procedures
• Age 18 to 90
• Diagnosis of major depressive disorder by DSM-5 criteria
• Depressive symptoms are thought to be caused primarily by a major depressive episode and not by some other neurologic or psychiatric illness
• Failure of or intolerance to at least 2 antidepressant treatments of different therapeutic classes (can include psychotherapy trial or neurostimulation trial)
• Meets criteria for clinical eligibility for ECT treatment, including optimization of any medical conditions and completion of any medical testing or clearance as clinically indicated
• Able to consent voluntarily to treatment
• Score of at least 2 on the MADRS item 10
• Ability to sit or lie down for an extended period of time and willingness to adhere to the theta burst stimulation protocol

You may not qualify if:

• Presence of implanted ferromagnetic devices or materials, including cardiac pacemaker, cochlear implant, deep brain stimulation device, vagus nerve stimulation device, shrapnel, facial or scalp piercings that cannot be removed, or metallic face or head tattoos
• Pregnancy or lactation
• Previous bad reaction or intolerance to transcranial magnetic stimulation
• Febrile illness within 1 week
• Treatment with another investigational drug or other intervention within 30 days
• Recent substance abuse or use disorder within the past 6 months, excluding tobacco or infrequent cannabis use
• History of epilepsy or seizure disorder
• History of penetrating traumatic brain injury, multiple sclerosis, or history of brain surgery or intracranial hemorrhage
• Primary psychiatric or medical/neurologic illness other than MDD that is more likely to account for depressive symptoms, including severe personality disorder or psychotic illness
• Severe or moderate intellectual disability
• Major neurocognitive disorder
• Involuntary commitment or petition filed for involuntary ECT treatment

Sponsors & Collaborators

• University of Iowa: lead

Related Publications (14)

• Perera T, George MS, Grammer G, Janicak PG, Pascual-Leone A, Wirecki TS. The Clinical TMS Society Consensus Review and Treatment Recommendations for TMS Therapy for Major Depressive Disorder. Brain Stimul. 2016 May-Jun;9(3):336-346. doi: 10.1016/j.brs.2016.03.010. Epub 2016 Mar 16.

  PMID: 27090022 BACKGROUND

• 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 BACKGROUND

• George MS, Lisanby SH, Avery D, McDonald WM, Durkalski V, Pavlicova M, Anderson B, Nahas Z, Bulow P, Zarkowski P, Holtzheimer PE 3rd, Schwartz T, Sackeim HA. Daily left prefrontal transcranial magnetic stimulation therapy for major depressive disorder: a sham-controlled randomized trial. Arch Gen Psychiatry. 2010 May;67(5):507-16. doi: 10.1001/archgenpsychiatry.2010.46.

  PMID: 20439832 BACKGROUND

• 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 BACKGROUND

• Peng Z, Zhou C, Xue S, Bai J, Yu S, Li X, Wang H, Tan Q. Mechanism of Repetitive Transcranial Magnetic Stimulation for Depression. Shanghai Arch Psychiatry. 2018 Apr 25;30(2):84-92. doi: 10.11919/j.issn.1002-0829.217047.

  PMID: 29736128 BACKGROUND

• Williams NR, Sudheimer KD, Bentzley BS, Pannu J, Stimpson KH, Duvio D, Cherian K, Hawkins J, Scherrer KH, Vyssoki B, DeSouza D, Raj KS, Keller J, Schatzberg AF. High-dose spaced theta-burst TMS as a rapid-acting antidepressant in highly refractory depression. Brain. 2018 Mar 1;141(3):e18. doi: 10.1093/brain/awx379. No abstract available.

  PMID: 29415152 BACKGROUND

• Friedrich MJ. Depression Is the Leading Cause of Disability Around the World. JAMA. 2017 Apr 18;317(15):1517. doi: 10.1001/jama.2017.3826. No abstract available.

  PMID: 28418490 BACKGROUND

• Zhan Y, Zhang B, Zhou Y, Zheng W, Liu W, Wang C, Li H, Chen L, Yu L, Walter M, Li M, Li MD, Ning Y. A preliminary study of anti-suicidal efficacy of repeated ketamine infusions in depression with suicidal ideation. J Affect Disord. 2019 May 15;251:205-212. doi: 10.1016/j.jad.2019.03.071. Epub 2019 Mar 22.

  PMID: 30927581 BACKGROUND

• Baeken C. Accelerated rTMS: A Potential Treatment to Alleviate Refractory Depression. Front Psychol. 2018 Oct 31;9:2017. doi: 10.3389/fpsyg.2018.02017. eCollection 2018.

  PMID: 30429807 BACKGROUND

• Feffer K, Lee HH, Mansouri F, Giacobbe P, Vila-Rodriguez F, Kennedy SH, Daskalakis ZJ, Blumberger DM, Downar J. Early symptom improvement at 10 sessions as a predictor of rTMS treatment outcome in major depression. Brain Stimul. 2018 Jan-Feb;11(1):181-189. doi: 10.1016/j.brs.2017.10.010. Epub 2017 Oct 19.

  PMID: 29107623 BACKGROUND

• Hawley CJ, Gale TM, Sivakumaran T; Hertfordshire Neuroscience Research group. Defining remission by cut off score on the MADRS: selecting the optimal value. J Affect Disord. 2002 Nov;72(2):177-84. doi: 10.1016/s0165-0327(01)00451-7.

  PMID: 12200208 BACKGROUND

• Kerner N, Prudic J. Current electroconvulsive therapy practice and research in the geriatric population. Neuropsychiatry (London). 2014 Feb;4(1):33-54. doi: 10.2217/npy.14.3.

  PMID: 24778709 BACKGROUND

• Guse B, Falkai P, Wobrock T. Cognitive effects of high-frequency repetitive transcranial magnetic stimulation: a systematic review. J Neural Transm (Vienna). 2010 Jan;117(1):105-22. doi: 10.1007/s00702-009-0333-7. Epub 2009 Oct 27.

  PMID: 19859782 BACKGROUND

• George MS, Raman R, Benedek DM, Pelic CG, Grammer GG, Stokes KT, Schmidt M, Spiegel C, Dealmeida N, Beaver KL, Borckardt JJ, Sun X, Jain S, Stein MB. A two-site pilot randomized 3 day trial of high dose left prefrontal repetitive transcranial magnetic stimulation (rTMS) for suicidal inpatients. Brain Stimul. 2014 May-Jun;7(3):421-31. doi: 10.1016/j.brs.2014.03.006. Epub 2014 Mar 19.

  PMID: 24731434 BACKGROUND

MeSH Terms

Conditions

Depressive Disorder, Major; Suicide; Epilepsy, Rolandic; Depression; Suicidal Ideation

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Self-Injurious Behavior; Behavioral Symptoms; Behavior; Epilepsies, Partial; Epilepsy; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epileptic Syndromes

Study Officials

• Nicholas Trapp, MD

  University of Iowa

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Benjamin Pace, MS

CONTACT

(319) 384-9302; benjamin-pace@uiowa.edu

Nicholas Trapp, MD

CONTACT

(319) 467-8188; nicholas-trapp@uiowa.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Investigator and outcomes assessor will be blinded to patient's designation.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Psychiatry

Model Details: Single-blind with crossover of experimental (aiTBS) group into standard of care (ECT) group.

Study Record Dates

• First Submitted: June 18, 2020
• First Posted: June 22, 2020
• Study Start (Estimated): December 1, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): July 1, 2030
• Last Updated: May 20, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share