Major Depressive DisorderRAPIDNCT04441008
Accelerated iTBS for Depression and Suicidality
A study testing Accelerated Intermittent Theta Burst (aiTBS) and Electroconvulsive therapy (ECT) in people with Major Depressive Disorder and Suicide, run by University of Iowa.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Major Depressive Disorder, Suicide
- What is being tested?
- Accelerated Intermittent Theta Burst (aiTBS) and Electroconvulsive therapy (ECT)
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- No sites listed yet
- Study dates
- Dec 2026to Jul 2030
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- • 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)
Show all 10Show fewer
- 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
Who cannot join
- • 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
Show all 12Show fewer
- 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
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Radical aiTBS Protocol for Intractable Depression
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
- Being tested
- Accelerated Intermittent Theta Burst (aiTBS), Electroconvulsive therapy (ECT)
- Keywords
- transcranial magnetic stimulation, theta burst, accelerated TMS, ECT, electroconvulsive therapy, depression, suicidality
- Medical subject headings
- Depressive Disorder, Major, Suicide, Epilepsy, Rolandic, Depression, Suicidal Ideation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Accelerated Intermittent Theta Burst (aiTBS)Device
Also called SAINT Protocol, accelerated TMS
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)Device
ECT as per standard clinical care and management.
| Study group | Role | What they receive |
|---|---|---|
| aiTBS arm | Experimental | aiTBS treatment as lead-in phase to ECT standard of care treatment. Receives: Device: Accelerated Intermittent Theta Burst (aiTBS); Device: Electroconvulsive therapy (ECT) |
| ECT arm | Active comparator | ECT as clinically indicated. Receives: Device: Electroconvulsive therapy (ECT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 5 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jun 2020
- Study startDec 2026 (estimated)
- Primary completionDec 2028 (estimated)
- Study completionJul 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (14)Papers the sponsor has linked to this study.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Single-blind with crossover of experimental (aiTBS) group into standard of care (ECT) group.
- Masking
- Double blind
- Who is masked
- Investigator, Outcomes assessor
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Iowa
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Nicholas Trapp, University of Iowa
- Investigators
- Nicholas Trapp, MD, Principal investigator, University of Iowa
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04441008
- Sponsor's protocol ID
- 202002608
- Acronym
- RAPID
- Status last verified
- May 2025
- First submitted
- 18 Jun 2020
- Last updated
- 20 May 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
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.
PubMed 27090022Levkovitz 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.
PubMed 25655160George 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.
PubMed 20439832Blumberger 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.
PubMed 29726344Peng 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.
PubMed 29736128Williams 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.
PubMed 29415152Friedrich 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.
PubMed 28418490Zhan 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.
PubMed 30927581Baeken 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.
PubMed 30429807Feffer 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.
PubMed 29107623Hawley 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.
PubMed 12200208Kerner 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.
PubMed 24778709Guse 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.
PubMed 19859782George 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.
PubMed 24731434
Study at a glance
From the registry record, last updated by the sponsor on 20 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Radical aiTBS Protocol for Intractable Depression
- ClinicalTrials.gov ID
- NCT04441008
- Acronym / sponsor ID
- RAPID / 202002608
- Conditions
- Major Depressive Disorder, Suicide
- Keywords
- transcranial magnetic stimulation, theta burst, accelerated TMS, ECT, electroconvulsive therapy, depression, suicidality
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- University of IowaUniversity, hospital or other
- Study start
- Dec 2026 (estimated)
- Primary completion
- Dec 2028 (estimated)
- Study completion
- Jul 2030 (estimated)
- First posted
- 22 Jun 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Single-blind with crossover of experimental (aiTBS) group into standard of care (ECT) group.
| Arm | Type | Receives |
|---|---|---|
| aiTBS arm | Experimental | Device: Accelerated Intermittent Theta Burst (aiTBS), Device: Electroconvulsive therapy (ECT)aiTBS treatment as lead-in phase to ECT standard of care treatment. |
| ECT arm | Active comparator | Device: Electroconvulsive therapy (ECT)ECT as clinically indicated. |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- • Ability to provide informed consent
Key exclusion criteria (12 listed)
- • 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Accelerated Intermittent Theta Burst (aiTBS)Also: SAINT Protocol, accelerated TMSHigh-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. | Device | aiTBS arm |
| Electroconvulsive therapy (ECT)ECT as per standard clinical care and management. | Device | ECT arm, aiTBS arm |
Primary outcome
Retention rate at completion of aiTBS vs the ECT group
Time frame: 5 days
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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 May 2025.
- Background: PubMed 27090022Perera 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.
- Background: PubMed 25655160Levkovitz 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.
- Background: PubMed 20439832George 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.
- Background: PubMed 29726344Blumberger 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.
- Background: PubMed 29736128Peng 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.
- Background: PubMed 29415152Williams 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.
- Background: PubMed 28418490Friedrich 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.
- Background: PubMed 30927581Zhan 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.
- Background: PubMed 30429807Baeken 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.
- Background: PubMed 29107623Feffer 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.
- Background: PubMed 12200208Hawley 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.
- Background: PubMed 24778709Kerner 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Nicholas Trapp, MD principal investigator
University of Iowa
Questions about this trial
What is this clinical trial studying?
A study testing Accelerated Intermittent Theta Burst (aiTBS) and Electroconvulsive therapy (ECT) in people with Major Depressive Disorder and Suicide, run by University of Iowa.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 20 May 2025. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Benjamin Pace, MS ((319) 384-9302, benjamin-pace@uiowa.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Retention rate at completion of aiTBS vs the ECT group (time frame: 5 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04441008, which also lists 14 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 May 2025.