One-Day cTBS Over the Precuneus (OcTOPUS)
One-Day cTBS Over the Precuneus (OcTOPUS)
The goal of this clinical trial is to learn whether two forms of one-day accelerated transcranial magnetic stimulation (TMS) can reduce depressive symptoms in adults with treatment-resistant depression. Treatment-resistant depression is depression that has not improved enough after at least two adequate antidepressant medication treatments. TMS is a non-invasive treatment that uses magnetic pulses to stimulate specific areas of the brain.
The main questions this study aims to answer are:
- Does continuous theta-burst stimulation (cTBS) targeting the precuneus reduce depressive symptoms 4 weeks after treatment compared with sham stimulation?
- Does intermittent theta-burst stimulation (iTBS) targeting the left dorsolateral prefrontal cortex reduce depressive symptoms 4 weeks after treatment compared with sham stimulation?
Researchers will compare precuneus cTBS, left dorsolateral prefrontal cortex iTBS, and sham stimulation to determine whether either active treatment reduces depressive symptoms more than sham stimulation. Participants will be randomly assigned to one of the three groups and will not be told which treatment they initially receive.
Participants will:
- Complete screening procedures and baseline assessments of depression, rumination, and cognitive function
- Receive 20 sessions of active or sham TMS during one in-person study day
- Complete follow-up assessments 1, 2, 3, and 4 weeks after the intervention
- Report any side effects or medical problems experienced during the study
Participants initially assigned to sham stimulation may choose to receive active TMS after completing the 4-week follow-up period. Those who choose this option will receive either precuneus cTBS or left dorsolateral prefrontal cortex iTBS and will complete additional follow-up assessments.
Visão geral do estudo
Status
Condições
Descrição detalhada
Treatment-resistant depression may involve dysfunction across distributed brain networks rather than a disturbance confined to a single brain region. The precuneus is a posterior hub of the default mode network and is involved in internally directed and self-referential processing. Altered interactions among the default mode, affective, and cognitive control networks have been implicated in depressive symptoms and rumination. In this study, precuneus continuous theta-burst stimulation (cTBS) is conceptualized as a hypothesis-driven network intervention that may modulate precuneus-centered network interactions implicated in depression.
A double-cone coil will be used to increase electric-field penetration toward the medial posteromedial cortex beneath the Pz scalp location of the international 10-20 electroencephalography system. Intermittent theta-burst stimulation (iTBS) of the left dorsolateral prefrontal cortex is included as an additional active treatment arm because this region is an established stimulation target for depression treatment. The three-arm design allows the novel precuneus target and the established left dorsolateral prefrontal cortex target to be evaluated within the same accelerated treatment framework and compared with sham stimulation.
Participants will be assigned to the three initial study groups using the minimal sufficient balance (MSB) randomization method, with sex and baseline depression severity, as measured by the Montgomery-Åsberg Depression Rating Scale, used as balancing factors. The target allocation ratio for the randomized, sham-controlled phase will be 1:1:1. Group allocation will be concealed from participants. Each active or sham intervention will consist of 20 stimulation sessions administered during a single day, with session onsets separated by approximately 30 minutes.
The primary efficacy analyses will use a longitudinal mixed-model framework to estimate treatment effects and evaluate the two prespecified active-versus-sham comparisons. The familywise type I error rate will be controlled across these two comparisons. The direct comparison between precuneus cTBS and left dorsolateral prefrontal cortex iTBS will be considered exploratory.
After completing the 4-week follow-up period, participants initially assigned to sham stimulation may elect to enter an open-label active TMS extension. Extension participants will be assigned to precuneus cTBS or left dorsolateral prefrontal cortex iTBS using the MSB method, with a target allocation ratio of 1:1. Sex and depression severity at the end of the sham-controlled phase, as measured by the Week 4 Montgomery-Åsberg Depression Rating Scale score, will be used as balancing factors. Because only a subset of participants assigned to sham stimulation is expected to enter the extension, extension analyses will be considered exploratory and hypothesis-generating.
Tipo de estudo
Inscrição (Estimado)
Estágio
- Não aplicável
Contactos e Locais
Contato de estudo
- Nome: Hakjoo Kim Kim, Ph.D.
- Número de telefone: 979-777-0679
- E-mail: khj213@gmail.com
Locais de estudo
-
-
Massachusetts
-
Belmont, Massachusetts, Estados Unidos, 02478
- Recrutamento
- Mclean Hospital
-
Contato:
- Hakjoo Kim, PhD
- Número de telefone: 617-855-4203
- E-mail: hkim128@mclean.harvard.edu
-
Investigador principal:
- Hakjoo Kim, PhD
-
-
Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
- Adulto
- Adulto mais velho
Aceita Voluntários Saudáveis
Descrição
Inclusion Criteria:
- Age 18 years or older.
- Able to speak, read, and understand English sufficiently to complete the study assessments and provide informed consent independently.
- Diagnosis of major depressive disorder according to DSM-5-TR criteria, confirmed by a qualified physician.
- Treatment-resistant depression, defined as an inadequate response to at least two adequate trials of antidepressant pharmacotherapy.
- Patient Health Questionnaire-9 (PHQ-9) total score of 10 or higher.
Exclusion Criteria:
- Any condition identified through TMS safety screening that, in the judgment of a study physician, presents an unacceptable safety risk for TMS. Such conditions may include:
- A history of a serious adverse reaction during TMS treatment.
- A history of seizure.
- A history of stroke.
- A history of serious head injury or neurosurgery.
- Metal in the head outside the mouth, such as shrapnel, surgical clips, or metal fragments.
- An implanted device, such as a cardiac pacemaker, cochlear implant, medical pump, or intracardiac line.
- Frequent or severe headaches.
- Another brain-related condition or an illness that caused brain injury.
- A family history of epilepsy.
- Permanent tattoos on the head or neck.
- Current recreational drug use.
- Current pregnancy or possible pregnancy.
- Use of a medication or combination of medications, a recent medication change, or medication withdrawal that, in the judgment of a study physician, presents an unacceptable safety risk, including a clinically significant increase in seizure risk.
- Current or lifetime diagnosis of bipolar I disorder, bipolar II disorder, a schizophrenia spectrum disorder, or another primary psychotic disorder.
- Active suicidal ideation with intent or plan requiring immediate clinical intervention, or another acute safety concern that cannot be safely managed within the study.
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Solteiro
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
|
Experimental: Precuneus cTBS
Participants receive 20 sessions of active continuous theta-burst stimulation (cTBS) targeting the Pz location of the international 10-20 EEG system during a single day.
Stimulation is delivered using a double-cone coil at 80% of the participant's resting motor threshold.
Each session consists of 600 pulses delivered over approximately 40 seconds, for a total of 12,000 pulses.
Session onsets are separated by approximately 30 minutes.
If stimulation at 80% of resting motor threshold is not tolerated, the intensity may be reduced to the highest tolerable level.
|
Active continuous theta-burst stimulation is delivered to the Pz location of the international 10-20 EEG system to target the precuneus.
Stimulation is administered with a double-cone coil at 80% of the participant's resting motor threshold.
Each session consists of 600 pulses delivered over approximately 40 seconds.
Participants receive 20 sessions during a single day, for a total of 12,000 pulses, with session onsets separated by approximately 30 minutes.
If 80% of resting motor threshold is not tolerated, the intensity may be reduced to the highest tolerable level.
Outros nomes:
|
|
Experimental: Left dlPFC iTBS
Participants receive 20 sessions of active intermittent theta-burst stimulation (iTBS) targeting the left dorsolateral prefrontal cortex during a single day.
The target is identified using the Beam F3 method, and stimulation is delivered using a figure-of-eight coil at 80% of the participant's resting motor threshold.
Each session consists of 600 pulses delivered over approximately 3 minutes, for a total of 12,000 pulses.
Session onsets are separated by approximately 30 minutes.
If stimulation at 80% of resting motor threshold is not tolerated, the intensity may be reduced to the highest tolerable level.
|
Active intermittent theta-burst stimulation is delivered to the left dorsolateral prefrontal cortex.
The stimulation target is identified using the Beam F3 method.
Stimulation is administered with a figure-of-eight coil at 80% of the participant's resting motor threshold.
Each session consists of 600 pulses delivered over approximately 3 minutes.
Participants receive 20 sessions during a single day, for a total of 12,000 pulses, with session onsets separated by approximately 30 minutes.
If 80% of resting motor threshold is not tolerated, the intensity may be reduced to the highest tolerable level.
Outros nomes:
|
|
Comparador Falso: Sham TMS
Participants receive 20 sessions of sham TMS at the left dorsolateral prefrontal cortex location identified using the Beam F3 method during a single day.
A figure-of-eight coil is inverted so that the active surface faces away from the scalp.
The device is operated at 80% of the participant's resting motor threshold, and sham stimulation follows the same stimulation pattern and approximate 3-minute duration as active iTBS.
Session onsets are separated by approximately 30 minutes.
After completing the Week 4 assessment, participants may enter an optional open-label extension and are randomized to receive active precuneus cTBS or left dlPFC iTBS.
|
Sham transcranial magnetic stimulation is administered at the left dorsolateral prefrontal cortex location identified using the Beam F3 method.
A figure-of-eight coil is inverted so that the active surface faces away from the scalp.
The stimulator is operated at 80% of the participant's resting motor threshold using the same intermittent theta-burst timing and approximate session duration as the active left dorsolateral prefrontal cortex intervention.
Participants receive 20 sham sessions during a single day, with session onsets separated by approximately 30 minutes.
Outros nomes:
|
O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score at Week 4
Prazo: Baseline and 1, 2, 3, and 4 weeks after the intervention
|
The MADRS is a clinician-administered 10-item scale used to assess the severity of depressive symptoms.
Each item is scored from 0 to 6, yielding a total score ranging from 0 to 60. Higher scores indicate greater depressive symptom severity.
MADRS total scores will be assessed at baseline and at Weeks 1, 2, 3, and 4 after the intervention.
Post-intervention scores will be compared between treatment groups with adjustment for baseline MADRS total score.
The primary treatment comparison will be conducted at Week 4.
|
Baseline and 1, 2, 3, and 4 weeks after the intervention
|
Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
17-Item Hamilton Depression Rating Scale (HAM-D-17) Total Score Through Week 4
Prazo: Baseline and 1, 2, 3, and 4 weeks after the intervention
|
The HAM-D-17 is a clinician-administered 17-item scale used to assess the severity of depressive symptoms.
The total score ranges from 0 to 52, with higher scores indicating greater depressive symptom severity.
HAM-D-17 total scores will be assessed at baseline and at Weeks 1, 2, 3, and 4 after the intervention.
Post-intervention scores will be compared between treatment groups with adjustment for baseline HAM-D-17 total score.
|
Baseline and 1, 2, 3, and 4 weeks after the intervention
|
|
Patient Health Questionnaire-9 (PHQ-9) Total Score Through Week 4
Prazo: Baseline and 1, 2, 3, and 4 weeks after the intervention
|
The PHQ-9 is a 9-item self-report measure used to assess depressive symptom severity.
Each item is scored from 0 to 3, yielding a total score ranging from 0 to 27.
Higher scores indicate greater depressive symptom severity.
PHQ-9 total scores will be assessed at baseline and at Weeks 1, 2, 3, and 4 after the intervention.
Post-intervention scores will be compared between treatment groups with adjustment for baseline PHQ-9 total score.
|
Baseline and 1, 2, 3, and 4 weeks after the intervention
|
|
Ruminative Responses Scale (RRS) Total Score Through Week 4
Prazo: Baseline and 1, 2, 3, and 4 weeks after the intervention
|
The RRS is a 22-item self-report measure used to assess the tendency to engage in ruminative responses.
Each item is scored from 1 to 4, yielding a total score ranging from 22 to 88.
Higher scores indicate greater levels of rumination.
RRS total scores will be assessed at baseline and at Weeks 1, 2, 3, and 4 after the intervention.
Post-intervention scores will be compared between treatment groups with adjustment for baseline RRS total score.
|
Baseline and 1, 2, 3, and 4 weeks after the intervention
|
|
Montreal Cognitive Assessment (MoCA) Total Score at Week 4
Prazo: Baseline and 4 weeks after the intervention
|
The MoCA is a clinician-administered cognitive screening measure that assesses multiple cognitive domains.
The total score ranges from 0 to 30, with higher scores indicating better cognitive performance.
MoCA total scores will be assessed at baseline and at Week 4 after the intervention.
The Week 4 score will be compared between treatment groups with adjustment for baseline MoCA total score.
|
Baseline and 4 weeks after the intervention
|
|
MGH/McLean Objective Neurocognitive Assessment (MONA) Total Score at Week 4
Prazo: Baseline and 4 weeks after the intervention
|
The MONA is an objective neurocognitive assessment that evaluates multiple cognitive domains.
The total score ranges from 0 to 30, with higher scores indicating better cognitive performance.
MONA total scores will be assessed at baseline and at Week 4 after the intervention.
The Week 4 score will be compared between treatment groups with adjustment for baseline MONA total score.
|
Baseline and 4 weeks after the intervention
|
Colaboradores e Investigadores
Patrocinador
Publicações e links úteis
Publicações Gerais
- 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.
- Sendi M, Halko M, Traynor J, Brown J, Copersino M, Nickerson L, Harnett N, van Rooij S, Pizzagalli D, House S, Beaudoin F, An X, Neylan T, Clifford G, Jovanovic T, Linnstaedt S, Germine L, Bollen K, Rauch S, Haran J, Storrow A, Lewandowski C, Musey P Jr, Hendry P, Sheikh S, Jones C, Punches B, Swor R, Gentile N, Hudak L, Pascual J, Seamon M, Harris E, Pearson C, Peak D, Domeier R, Rathlev N, O'Neil B, Sergot P, Sanchez L, Bruce S, Sheridan J, Harte S, Kessler R, Koenen K, Phelps E, Salat D, Mayberg H, McLean S, Stevens J, Calhoun V, Ressler K, Dillon D. Comprehensive mapping of cognitive and emotion networks in stress, anxiety, and depression implicates the precuneus as a critical hub. Res Sq [Preprint]. 2025 Aug 26:rs.3.rs-7200801. doi: 10.21203/rs.3.rs-7200801/v1.
- Kim H, Halko M, Copersino ML, Traynor J, Dillon D, Sendi M, Razafsha M, Uflacker A, Bharathan AV, Coyle M, Ganesh P, Nolan J, Parlikar RU, Pettibone T, Gunadeva N, Hur KH, Downar J, McGirr A, Ressler K, Brown J. 6 - Depression and Anxiety Symptom Change Following One-Day Ultra-Accelerated TMS Targeting dlPFC or Network-Guided Precuneus: Preliminary Findings. Transcranial Magnetic Stimulation. 2026;7(Suppl 1):100228. doi:10.1016/j.transm.2026.100228
- Vaughn DA, Marino B, Engelbertson A, Dojnov A, Johnson L, Stine M, Vila-Rodriguez F, Weiss N, Nanos G, Downar J. Real-world effectiveness of a single-day regimen for transcranial magnetic stimulation using Optimized, Neuroplasticity-Enhanced techniques in Depression (ONE-D): An open-label case series. Transcranial Magnetic Stimulation. 2025;5:100200. doi:10.1016/j.transm.2025.100200
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Real)
Conclusão Primária (Estimado)
Conclusão do estudo (Estimado)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Real)
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
Outros números de identificação do estudo
- 2026P001989
Plano para dados de participantes individuais (IPD)
Planeja compartilhar dados de participantes individuais (IPD)?
Descrição do plano IPD
Informações sobre medicamentos e dispositivos, documentos de estudo
Estuda um medicamento regulamentado pela FDA dos EUA
Estuda um produto de dispositivo regulamentado pela FDA dos EUA
produto fabricado e exportado dos EUA
Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .