Accelerated iTBS for Depression and Suicidality

Major Depressive Disorder Clinical Trial

— RAPID  

Official title:

Radical aiTBS Protocol for Intractable Depression

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04441008
• Other study ID #: 202002608
• Status: Not yet recruiting
• Phase: N/A
• Start date: December 2025
• Est. completion date: July 2029

Study information

• Verified date: March 2024
• Source: University of Iowa
• Contact: Benjamin Pace, MS
• Phone: (319) 384-9302
• Email: benjamin-pace[@]uiowa.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 50
• Est. completion date: July 2029
• Est. primary completion date: December 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Major Depressive Disorder
• Suicide

Intervention

Device:
• 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.
• Electroconvulsive therapy (ECT)
ECT as per standard clinical care and management.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
University of Iowa

References & Publications (14)

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. — View 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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View 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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. Erratum In: J Affect Disord. 2020 Sep 1;274:1220. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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