Accelerated iTBS for Depression and Suicidality

NCT ID: NCT04441008

Last Updated: 2025-05-20

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

NOT_YET_RECRUITING

Clinical Phase

NA

Total Enrollment

50 participants

Study Classification

INTERVENTIONAL

Study Start Date

2026-12-31

Study Completion Date

2030-07-31

Brief Summary

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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.

Detailed Description

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Conditions

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Major Depressive Disorder Suicide

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Single-blind with crossover of experimental (aiTBS) group into standard of care (ECT) group.
Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Investigators Outcome Assessors
Investigator and outcomes assessor will be blinded to patient's designation.

Study Groups

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aiTBS arm

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

Group Type EXPERIMENTAL

Accelerated Intermittent Theta Burst (aiTBS)

Intervention Type 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.

Electroconvulsive therapy (ECT)

Intervention Type DEVICE

ECT as per standard clinical care and management.

ECT arm

ECT as clinically indicated.

Group Type ACTIVE_COMPARATOR

Electroconvulsive therapy (ECT)

Intervention Type DEVICE

ECT as per standard clinical care and management.

Interventions

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Accelerated Intermittent Theta Burst (aiTBS)

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.

Intervention Type DEVICE

Electroconvulsive therapy (ECT)

ECT as per standard clinical care and management.

Intervention Type DEVICE

Other Intervention Names

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SAINT Protocol, accelerated TMS

Eligibility Criteria

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Inclusion Criteria

* • 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

Exclusion Criteria

* • 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
Minimum Eligible Age

18 Years

Maximum Eligible Age

90 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Iowa

OTHER

Sponsor Role lead

Responsible Party

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Nicholas Trapp

Assistant Professor of Psychiatry

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Nicholas Trapp, MD

Role: PRINCIPAL_INVESTIGATOR

University of Iowa

Central Contacts

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Benjamin Pace, MS

Role: CONTACT

(319) 384-9302

Nicholas Trapp, MD

Role: CONTACT

(319) 467-8188

References

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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.

Reference Type BACKGROUND
PMID: 27090022 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25655160 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20439832 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29726344 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29736128 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29415152 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28418490 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30927581 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30429807 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29107623 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12200208 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24778709 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19859782 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24731434 (View on PubMed)

Other Identifiers

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202002608

Identifier Type: -

Identifier Source: org_study_id

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