TMS Targeting Methods for Depression

(XRnav Trial)

Overseen By Christoph Leuze, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Stanford University

Must be taking: Psychotropic

Disqualifiers: Neurological disorders, Metal implants, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 9 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how different methods of targeting transcranial magnetic stimulation (TMS) can help treat depression. It compares a mixed reality device with traditional scalp measurements and commercial neuronavigation systems. The goal is to determine if the mixed reality device can make treatments faster and easier for technicians, potentially improving patient outcomes. The trial seeks participants with treatment-resistant depression who are already set to receive TMS, excluding those with metal implants or a history of severe neurological disorders. As an unphased trial, this study provides a unique opportunity to contribute to innovative research that could enhance future depression treatments.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, it mentions that clinical subjects should have a diagnosis of treatment-resistant depression and be prescribed a course of treatment with rTMS, which suggests you may need to continue your current treatment.

What prior data suggests that this mixed reality device is safe for TMS targeting?

Studies have shown that transcranial magnetic stimulation (TMS) is generally safe and well-tolerated for treating major depressive disorder. TMS uses magnets to stimulate nerve cells in the brain. Previous research tested a guiding system called neuronavigation to improve the precision of these magnets. The mixed reality device in this trial aims to make this process faster and easier.

Specific safety data on the new mixed reality approach is not yet available. However, since TMS is already used safely for depression and neuronavigation has been tested in patients, the trial treatment is expected to be safe. It is important to consult a healthcare provider to understand any potential risks or side effects before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores innovative ways to enhance the precision of transcranial magnetic stimulation (TMS) for treating depression. Unlike standard TMS, which often relies on basic scalp measurements to determine where to apply stimulation, this trial incorporates mixed reality neuronavigation. This method uses advanced technology to more accurately target the brain areas involved in depression, potentially increasing the treatment's effectiveness. By refining the delivery of TMS, researchers hope to improve outcomes for patients with depression, offering them a more tailored and potentially faster-acting option.

What evidence suggests that this trial's methods could be effective for depression?

Research shows that mixed reality devices can enhance the use of transcranial magnetic stimulation (TMS) for treating depression. In this trial, one group will receive TMS with mixed reality neuronavigation, which helps identify the precise brain areas to target, potentially increasing the treatment's effectiveness compared to the traditional scalp measurement method. A recent study found that mixed reality streamlines this process for doctors. This method has shown promise in reducing depression symptoms by enabling precise and efficient targeting of brain areas. Overall, mixed reality could make TMS treatment for depression more effective and user-friendly. ^{1 2 4 6 7}

Who Is on the Research Team?

Jennifer A McNab, PhD

Principal Investigator

Stanford University

Are You a Good Fit for This Trial?

This trial is for adults aged 18-75 with treatment-resistant depression who are prescribed transcranial magnetic stimulation (TMS) therapy. They must be MRI-compatible, meaning no metal in the body and able to complete screening at specific centers. Excluded are those with neurological disorders, pacemakers or certain implants, and a history of substance abuse.

Inclusion Criteria

I have depression that hasn't improved with standard treatments and am prescribed rTMS.

MRI scanning eligibility, including no evidence of any form of metal embedded in the body

Healthy subjects with no history of any Axis I psychiatric disorder, are taking psychotropic medication, or use illicit drugs

Exclusion Criteria

Any contraindication to being scanned in the 3.0T scanner at the Lucas Center or CNI such as having a pacemaker or implanted device that has not been cleared for scanning at 3.0 Tesla

I have no history of major neurological disorders or brain-related treatments.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 30 daily weekday repetitive TMS treatments for 6 weeks, followed by 6 additional treatments tapered over 3 weeks

9 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Mixed reality neuronavigation
• Transcranial Magnetic Simulation

Trial Overview The study tests if using mixed reality devices can improve TMS targeting for treating depression compared to traditional scalp measurements or commercial neuronavigation systems. It aims to see if this method reduces setup time and is practical in clinical settings.

How Is the Trial Designed?

Group I: No neuronavigation Active Control 1 Intervention

For this group, the stimulation location for repetitive transcranial stimulation treatment is estimated by the clinician via scalp measurements.

Group II: Mixed reality neuronavigation Active Control 2 Interventions

For this group, the stimulation location for repetitive transcranial stimulation treatment is estimated by the clinician via a mixed reality neuronavigation device.

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

Published Research Related to This Trial

Transcranial magnetic stimulation (TMS) is safe to use with implanted deep brain stimulation (DBS) devices at low to moderate intensities, as no movement or temperature increase was observed during stimulation at 0.2 Hz with 100% intensity for 1 hour.

However, caution is advised when using high-intensity TMS (over 50%) near looped DBS leads, as it can exceed the safety limit for charge density, potentially leading to electrical tissue injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety of transcranial magnetic stimulation with deep brain stimulation instruments. Shimojima, Y., Morita, H., Nishikawa, N., et al.[2010]

Transcranial magnetic stimulation (TMS) is a non-invasive brain imaging technique that can causally link specific cortical areas to physiological responses, making it more precise than other imaging methods.

Navigated TMS has shown clinical effectiveness in mapping motor areas, assessing recovery after stroke, and treating conditions like depression, but further development of targeting and dosing protocols is needed for improved accuracy and reproducibility in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Navigated transcranial magnetic stimulation. Ruohonen, J., Karhu, J.[2016]

Transcranial magnetic stimulation (TMS) is a non-invasive technique that uses magnetic fields to stimulate specific areas of the brain, revealing new insights into brain function and recovery processes, such as those following a stroke.

Over 15 years, TMS has contributed to understanding complex brain functions, including the neuronal basis of consciousness, and is particularly effective when combined with imaging techniques like magnetic resonance imaging (MRI).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Ferrier Lecture 2004 what can transcranial magnetic stimulation tell us about how the brain works? Cowey, A.[2023]

Transcranial magnetic stimulation (TMS) is shown to be safe for patients with major depressive disorder, with no significant increase in dropout rates or serious adverse events compared to sham treatment, based on a meta-analysis of 53 trials involving 3,273 participants.

While TMS may lead to some mild and transient non-serious adverse events like headaches and discomfort, these side effects are manageable, suggesting that TMS can be a viable treatment option either alone or alongside other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of transcranial magnetic stimulation in unipolar depression: A systematic review and meta-analysis of randomized-controlled trials. Wang, WL., Wang, SY., Hung, HY., et al.[2022]

Transcranial magnetic stimulation (TMS) was effective in treating treatment-resistant depression, with a response rate of 50.6% and a remission rate of 24.7% after 6 weeks of treatment in a cohort of 100 patients.

TMS was well tolerated, showing a low discontinuation rate of 3% and no serious adverse events, indicating its safety as an adjunctive treatment for patients who have not responded to other antidepressant therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of transcranial magnetic stimulation in clinical practice post-FDA approval in the United States: results observed with the first 100 consecutive cases of depression at an academic medical center. Connolly, KR., Helmer, A., Cristancho, MA., et al.[2022]

In a study of 46 patients with drug-resistant depression, using a neuronavigated MR-less rTMS system allowed for targeted stimulation of different brain regions, leading to varying clinical outcomes and physiological effects.

Group 3, which received stimulation at a specific target, showed the greatest reduction in depression symptoms (66.94% decrease in HAM-D scores), suggesting that precise targeting in rTMS can enhance treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of MR‑less MNI based neuronavigation for 10 Hz rTMS depression therapy: electrophysiological and clinical implications. Valiulis, V., Gerulskis, G., Dapšys, K., et al.[2019]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40424301/

a double-blind, multicenter randomized controlled trial This evaluator- and patient-blind, multicenter RCT assessed the superiority in terms of efficacy of 10 HF rTMS sessions of the left DLPFC targeted with MRI ...

2. withpower.com withpower.com/trial/phase-depressive-disorder-2024-d4e1a

TMS Targeting Methods for Depression (XRnav Trial) Trial Overview The study tests if using mixed reality devices can improve TMS targeting for treating depression compared to traditional scalp measurements or ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11921824/

A Pilot Trial of Stepwise Implementation of Virtual Reality ... This stepwise protocol shows promise in providing an approach to rapidly improve symptoms of dysphoria in transdiagnostic populations.

4. nature.com nature.com/articles/s41598-023-41044-1

Robotic transcranial magnetic stimulation in the treatment ... In this study, we not only developed a custom-TMS robot for better TMS coil placement but also analyzed the therapeutic effects on depression.

5. med.stanford.edu med.stanford.edu/immers/Publications/PublicationHighlights/TMS-depression.html

Mixed-Reality Guidance for Brain Stimulation Treatment of ... In this paper we present tools for the development of a mixed reality TMS neuronavigation setup that will integrate patient tracking and visualization of brain ...

6. researchgate.net researchgate.net/publication/392129771_Repetitive_Transcranial_Magnetic_Stimulation_targeted_with_MRI_based_neuro-navigation_in_major_depressive_episode_a_double-blind_multicenter_randomized_controlled_trial

a double-blind, multicenter randomized controlled trial 105 patients were randomized and 92 were evaluable with respectively 45 patients in. the neuronavigation group and 47 in the standard group.

7. neuroscience.stanford.edu neuroscience.stanford.edu/our-science/funded-projects/mixed-reality-neuronavigation-tms-treatment-depression

Mixed-reality neuronavigation for TMS treatment of depression This team is developing a cutting-edge mixed reality application to improve the targeted delivery of transcranial magnetic stimulation (TMS).