50 Participants Needed

rTMS for Depression

CK
Overseen ByCorey Keller, MD, PhD
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Approved in 3 JurisdictionsThis treatment is already approved in other countries

What You Need to Know Before You Apply

What is the purpose of this trial?

Depression is a highly prevalent condition characterized by persistent low mood, energy, and activity that can affect one's thoughts, mood, behavior, and sense of well-being. Repetitive transcranial magnetic stimulation (rTMS), a non-invasive neuromodulatory technique, is an effective treatment for depression when targeting the dorsolateral prefrontal cortex (dlPFC) of the central executive network (CEN). However, remission rates are suboptimal and individual methods to target the dlPFC are lacking. In this study, we will enroll 50 patients with major depression and in a single rTMS 'dose,' prospective, randomized, double-blind, cross-over design will assess whether rTMS targeted to an individual's central executive network (CEN) assessed by single pulse TMS can enhance network modulation. If successful, this work will lead to a clinical rTMS trial comparing this personalized targeting approach against standard rTMS.

Will I have to stop taking my current medications?

The trial requires that you do not take any 'as needed' medications within 24 hours of your study appointment and you cannot be on medications that lower the seizure threshold, like olanzapine, chlorpromazine, or lithium.

Is rTMS safe for humans?

Repetitive transcranial magnetic stimulation (rTMS) is generally considered safe for treating depression, with studies showing it is well-tolerated by most people. Common side effects are mild and may include headaches or scalp discomfort, but serious side effects are rare.12345

How is the treatment Individualized CEN-targeted rTMS different from other treatments for depression?

Individualized CEN-targeted rTMS is unique because it uses personalized brain imaging to tailor the treatment to each patient's specific brain structure and connectivity, potentially improving its effectiveness compared to standard rTMS protocols.678910

What data supports the effectiveness of the treatment Individualized CEN-targeted rTMS for depression?

Research suggests that repetitive transcranial magnetic stimulation (rTMS) can be effective for treatment-resistant depression, especially when personalized to the patient's specific brain characteristics and symptoms. Studies indicate that targeting specific brain areas and using navigation systems to guide rTMS can improve its antidepressant effects.68111213

Are You a Good Fit for This Trial?

This trial is for adults aged 18-65 with major depression, as confirmed by a clinical interview. Participants must understand English, have no seizure risk or neurological disorders, not be using certain medications or substances, and not be pregnant. They should also have a significant level of depression severity.

Inclusion Criteria

PHQ9 > 10 for disease severity
Must comprehend English well to ensure adequate comprehension of the EEG and TMS instructions, and of clinical scales
Right-handed
See 4 more

Exclusion Criteria

Active substance abuse
I am taking medication that could make it easier for me to have seizures.
I have been diagnosed with a psychotic or bipolar disorder.
See 7 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Diagnostic Session

Participants undergo a diagnostic session including a Structured Clinical Interview for DSM5 (SCID-I62) and a PHQ9 assessment

1 session

MRI Session

Participants undergo a 30-minute MRI session to record structural brain data

30 minutes

Treatment

Participants receive rTMS targeting the dlPFC using different methods including individualized CEN targeting, structural MRI, and standard scalp targeting

4 sessions, each lasting 30 minutes
4 visits (in-person)

Sham rTMS

Participants receive a sham rTMS session to control for off-target effects

1 session, lasting 30 minutes

Follow-up

Participants are monitored for changes in TMS-EEG measures and behavioral changes in attention and working memory

Up to 2 hours

What Are the Treatments Tested in This Trial?

Interventions

  • Individualized CEN-targeted rTMS
  • Neuronavigated rTMS
  • Scalp-targeted rTMS
  • Sham rTMS
Trial Overview The study tests whether personalized rTMS targeting the central executive network can better improve symptoms in those with depression compared to standard approaches. It's a randomized and double-blind experiment involving different types of rTMS including sham (placebo) treatment.
How Is the Trial Designed?
4Treatment groups
Experimental Treatment
Active Control
Placebo Group
Group I: Individualized CEN-targeted rTMSExperimental Treatment2 Interventions
Individualized CEN-targeted rTMS will combine neuronavigated rTMS and single pulse TMS-EEG to identify the region of the dlPFC making the strongest connection with the parietal node of the CEN. First, regions of the dlPFC strongly connected to the parietal CEN will be identified by applying single TMS pulses in grid-like fashion to ROIs within the dlPFC. For each anatomical dlPFC subunit probed with TMS, the TMS-EEG response will be quantified in the parietal region of the CEN. The dlPFC subunit that demonstrates the strongest TMS-EEG response in parietal cortex will be chosen for rTMS. rTMS will last approximately 30 minutes (3000 pulses total) and will be delivered at 120% of the participant's motor threshold. Participants will be monitored during the rTMS session for adverse events and/or side effects.
Group II: Neuronavigated rTMSActive Control2 Interventions
Neuronavigated rTMS will be delivered using neuro-navigation based on participants' own MRI images to target the dlPFC. rTMS will last approximately 30 minutes (3000 pulses total) and will be delivered at 120% of the participant's motor threshold. Participants will be monitored during the rTMS session for adverse events and/or side effects.
Group III: Scalp-targeted rTMSActive Control2 Interventions
Scalp-targeted rTMS will be delivered using standard BEAM F3 targeting methodology to target the dlPFC. rTMS will last approximately 30 minutes (3000 pulses total) and will be delivered at 120% of the participant's motor threshold. Participants will be monitored during the rTMS session for adverse events and/or side effects.
Group IV: Sham rTMSPlacebo Group1 Intervention
Sham rTMS will be delivered for one session to mimic active rTMS conditions. To maximize sham validity, both 1) a direction- sensor TMS coil will alert the operators to flip the coil if the wrong side is being used, and 2) low-intensity electrical stimulation to match the active rTMS frequency will be applied to scalp electrodes under the coil for sham and placed but not activated in the active arm. The rTMS coil will be positioned using neuro-navigation based on participants' own MRI images, mimicking active rTMS. Sham rTMS will last approximately 30 minutes (3000 pulses total) and will be delivered at 120% of the participant's motor threshold. Participants will be monitored during the sham rTMS session for adverse events and/or side effects.

Individualized CEN-targeted rTMS is already approved in United States, European Union, Canada for the following indications:

🇺🇸
Approved in United States as rTMS for:
  • Major Depressive Disorder
  • Obsessive-Compulsive Disorder
  • Migraines
  • Smoking Cessation
🇪🇺
Approved in European Union as rTMS for:
  • Major Depressive Disorder
  • Obsessive-Compulsive Disorder
🇨🇦
Approved in Canada as rTMS for:
  • Major Depressive Disorder
  • Obsessive-Compulsive Disorder

Find a Clinic Near You

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials
2,527
Recruited
17,430,000+

Published Research Related to This Trial

A case study of a 40-year-old woman with drug-resistant depression showed that using a navigation system to accurately target the prefrontal cortex during rTMS led to more significant antidepressant effects compared to the standard targeting method.
The standard method for locating the prefrontal cortex may misidentify the target area, as it incorrectly stimulated Broca's area instead, highlighting the importance of precise targeting in rTMS for effective treatment.
The value of navigation-guided rTMS for the treatment of depression: an illustrative case.Lefaucheur, JP., Brugières, P., Ménard-Lefaucheur, I., et al.[2007]
Repetitive transcranial magnetic stimulation (rTMS) is a promising treatment for major depressive disorder (MDD), particularly for patients who do not respond to traditional therapies, and may be tailored to individual patient characteristics.
The review emphasizes the importance of identifying and validating patient-specific factors, such as genetic and neuroimaging biomarkers, to optimize rTMS treatment and move towards a personalized medicine approach in depression care.
Identification of Clinical Features and Biomarkers that may inform a Personalized Approach to rTMS for Depression.Garnaat, SL., Fukuda, AM., Yuan, S., et al.[2021]
In a study involving 41 patients with medication-refractory depression, the effectiveness of repetitive transcranial magnetic stimulation (rTMS) was significantly predicted by stimulation sites that were more anterolateral and had negative connectivity with the subgenual cingulate.
The strongest predictor of response to active rTMS was the functional connectivity between the stimulation site and the subgenual cingulate, suggesting that targeting this connectivity could enhance treatment outcomes for depression.
Prospective Validation That Subgenual Connectivity Predicts Antidepressant Efficacy of Transcranial Magnetic Stimulation Sites.Weigand, A., Horn, A., Caballero, R., et al.[2019]

Citations

The value of navigation-guided rTMS for the treatment of depression: an illustrative case. [2007]
Identification of Clinical Features and Biomarkers that may inform a Personalized Approach to rTMS for Depression. [2021]
Prospective Validation That Subgenual Connectivity Predicts Antidepressant Efficacy of Transcranial Magnetic Stimulation Sites. [2019]
Personalizing Repetitive Transcranial Magnetic Stimulation Parameters for Depression Treatment Using Multimodal Neuroimaging. [2022]
Has repetitive transcranial magnetic stimulation (rTMS) treatment for depression improved? A systematic review and meta-analysis comparing the recent vs. the earlier rTMS studies. [2018]
Personalized, parcel-guided rTMS for the treatment of major depressive disorder: Safety and proof of concept. [2023]
Transcranial magnetic stimulation (TMS) safety: a practical guide for psychiatrists. [2019]
Double-blind controlled investigation of bilateral prefrontal transcranial magnetic stimulation for the treatment of resistant major depression. [2019]
Transcranial magnetic stimulation for depression. [2017]
UNANSWERED QUESTIONS IN THE TRANSCRANIAL MAGNETIC STIMULATION TREATMENT OF PATIENTS WITH DEPRESSION. [2019]
A randomized controlled trial with 4-month follow-up of adjunctive repetitive transcranial magnetic stimulation of the left prefrontal cortex for depression. [2022]
12.United Statespubmed.ncbi.nlm.nih.gov
Using diffusion tensor imaging to effectively target TMS to deep brain structures. [2023]
An update on the clinical use of repetitive transcranial magnetic stimulation in the treatment of depression. [2021]
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