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

60 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a special headset that combines real and virtual elements to help doctors place a magnetic coil on the head more accurately during TMS treatment for depression. The goal is to see if this method improves treatment outcomes compared to traditional methods. Transcranial magnetic stimulation (TMS) is a relatively new technique used to treat depression by delivering magnetic radiation to the head using a hand-held coil.

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 data supports the effectiveness of the treatment Mixed reality neuronavigation, Transcranial Magnetic Simulation for depression?

Research shows that transcranial magnetic stimulation (TMS) is effective in treating major depression, especially when the stimulation is accurately targeted using neuronavigation systems. Studies indicate that daily TMS sessions over several weeks can significantly improve depression symptoms, and using precise targeting methods can enhance these effects. ^{1 2 3 4 5}

Is transcranial magnetic stimulation (TMS) safe for humans?

Transcranial magnetic stimulation (TMS) is generally considered safe for humans, with studies showing it is well-tolerated in treating major depressive disorder. Safety has been evaluated even in patients with implanted devices, and systematic reviews support its safety profile. ^{1 3 6 7 8}

How does the treatment 'TMS Targeting Methods for Depression' differ from other treatments for depression?

This treatment is unique because it uses mixed reality neuronavigation to precisely target specific brain areas with transcranial magnetic stimulation (TMS), improving accuracy and effectiveness compared to standard methods that often have errors in coil placement. ^{1 9 10 11 12}

Research Team

Jennifer A McNab, PhD

Principal Investigator

Stanford University

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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) 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]

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) 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 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]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

Assessment of standard coil positioning in transcranial magnetic stimulation in depression. [2011]

2. United States pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation of the prefrontal cortex in depression. [2022]

3. Poland pubmed.ncbi.nlm.nih.gov

The use of MR‑less MNI based neuronavigation for 10 Hz rTMS depression therapy: electrophysiological and clinical implications. [2019]

4. France pubmed.ncbi.nlm.nih.gov

Navigated transcranial magnetic stimulation. [2016]

5. United States 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. [2022]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Safety of transcranial magnetic stimulation in unipolar depression: A systematic review and meta-analysis of randomized-controlled trials. [2022]

7. England pubmed.ncbi.nlm.nih.gov

The safety of transcranial magnetic stimulation with deep brain stimulation instruments. [2010]

8. United States pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation in the treatment of major depressive disorder: a comprehensive summary of safety experience from acute exposure, extended exposure, and during reintroduction treatment. [2019]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Single-Subject TMS Pulse Visualization on MRI-Based Brain Model: A precise method for mapping TMS pulses on cortical surface. [2023]

10. Germany pubmed.ncbi.nlm.nih.gov

[A 3D FEM model for calculation of electromagnetic fields in transmagnetic stimulation]. [2019]

11. United States pubmed.ncbi.nlm.nih.gov

SlicerTMS: Interactive Real-time Visualization of Transcranial Magnetic Stimulation using Augmented Reality and Deep Learning. [2023]

12. England pubmed.ncbi.nlm.nih.gov

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