Virtual Reality-Guided TMS for Depression

No longer recruiting at 1 trial location

Overseen By Rashel Mejia, BS

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Soterix Medical

Must not be taking: Seizure risk medications

Disqualifiers: Psychotic disorder, Pregnancy, Claustrophobia, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new methods to guide Transcranial Magnetic Stimulation (TMS), a non-invasive treatment using magnetic fields to target specific brain areas, for individuals with major depressive disorder. The researchers aim to determine if virtual reality or online navigation can better pinpoint treatment areas and improve outcomes for those who have not responded to other depression treatments. This trial suits individuals currently experiencing moderate to severe depression who have not found relief with at least two previous treatments.

As an unphased trial, it offers a unique opportunity to explore innovative treatment methods that could potentially enhance participants' quality of life.

Will I have to stop taking my current medications?

You may need to stop taking certain medications that increase the risk of seizures or have a history of ketamine or MAOI use. If you are on allowed medications like antidepressants or anticonvulsants, your dose must be stable for at least four weeks before the study and remain the same during the study.

What prior data suggests that this virtual neuro-navigation package is safe for optimizing TMS treatment?

Research has shown that Transcranial Magnetic Stimulation (TMS) is a safe treatment for major depressive disorder (MDD). The FDA has approved TMS for MDD and other conditions, indicating it has passed strict safety tests for these uses.

Studies have found that patients generally tolerate TMS well. Most experience only mild side effects, such as slight headaches or scalp discomfort, which usually resolve quickly. The procedure is non-invasive, requiring no surgery or anesthesia.

Both virtual and online neuro-navigation TMS use MRI images to aim the treatment more precisely, targeting the right areas in the brain. While specific safety data for these navigation methods are still being gathered, TMS itself has a strong safety record.

In summary, TMS is generally considered safe, with any side effects typically mild and temporary. Always consult a healthcare provider to determine if it's the right choice. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the trial exploring Virtual Reality-Guided TMS for Depression because it leverages cutting-edge technology to enhance the precision of treatment. Unlike traditional TMS, which targets the brain based on general anatomical landmarks, this approach uses neuro-navigation to pinpoint treatment areas within the brain's L-DLPFC region using MR images. This method is tested in two ways: one using advanced software for virtual navigation and the other relying on human expertise for on-line navigation. By honing in on specific areas more accurately, the trial aims to improve the effectiveness of TMS in treating depression, potentially offering faster and more robust relief for patients.

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

Studies have shown that Transcranial Magnetic Stimulation (TMS) effectively treats depression. In this trial, participants will receive either virtual neuro-navigation TMS or on-line neuro-navigation TMS. Research indicates that virtual neuro-navigation TMS, which uses MRI scans to target specific brain areas, might improve outcomes by directing magnetic stimulation to the most effective parts of the brain. Evidence suggests that on-line neuro-navigation TMS offers more precise targeting, leading to more consistent results. Overall, TMS is FDA-approved and has proven safe and effective for major depressive disorder. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for adults with major depressive disorder who haven't improved after trying at least two depression treatments and TMS using standard methods. They must have moderate to severe depression, not be claustrophobic, free from psychotic disorders or recent substance abuse, not actively suicidal, able to consent, and not pregnant or breastfeeding.

Inclusion Criteria

My depression hasn't improved after trying two or more treatments and TMS.

At least moderate depression severity, operationalized as Montgomery-Asberg Depression Rating Scale (MADRS) score ≥ 20

I have been diagnosed with major depression.

Exclusion Criteria

I take medication that doesn't allow me to have TMS treatment.

Contraindications to MRI (based on metal screening form)

My health is stable; no recent issues found in exams or tests.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive TMS treatment targeting the L-DLPFC using either virtual or on-line neuro-navigation

6 weeks

2 visits per week (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Neuro-navigated Transcranial Magnetic Stimulation (TMS)

Trial Overview The study tests a virtual neuro-navigation system designed to improve the precision of TMS treatment for depression. It's a Phase I trial focusing on how well this new technology identifies specific brain targets to enhance the effectiveness of TMS.

How Is the Trial Designed?

Group I: virtual neuro-navigation Experimental Treatment 1 Intervention

The specific area within the L-DLPFC will be identified by a software using MR images. TMS will be administered to the identified area.

Group II: on-line neuro-navigation Experimental Treatment 1 Intervention

The specific area within the L-DLPFC will be identified by a person using MR images. TMS will be administered to the identified area.

Neuro-navigated Transcranial Magnetic Stimulation (TMS) is already approved in United States, European Union for the following indications:

Approved in United States as Navigated TMS for:

• Major Depressive Disorder (MDD)
• Obsessive-Compulsive Disorder (OCD)
• Chronic Pain Syndrome

Approved in European Union as Neuro-navigated TMS for:

• Treatment-resistant depression
• Obsessive-compulsive disorder
• Posttraumatic stress disorder
• Tourette disorder
• Chronic pain syndrome

Who Is Running the Clinical Trial?

Soterix Medical

Lead Sponsor

Trials

12

Recruited

410+

Columbia University

Collaborator

Trials

1,529

Recruited

2,832,000+

Published Research Related to This Trial

Neuronavigated low-frequency rTMS significantly enhances motor-evoked potentials and improves motor behavior, such as reaction time and grip strength, compared to non-navigated rTMS in healthy subjects.

The study involved 10 participants and demonstrated that navigated rTMS leads to more pronounced effects on the contralateral hemisphere, suggesting its potential for better therapeutic outcomes in stroke recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuronavigation increases the physiologic and behavioral effects of low-frequency rTMS of primary motor cortex in healthy subjects. Bashir, S., Edwards, D., Pascual-Leone, A.[2022]

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]

Navigated transcranial magnetic stimulation (TMS) combined with MRI allows for precise mapping of brain functions by accurately correlating the position of the stimulating coil on the scalp with the underlying cortical anatomy.

This technique enhances the reliability of TMS for localizing cortical functions, making it a valuable tool for preoperative planning in patients with brain lesions near critical areas like the rolandic cortex.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Introducing navigated transcranial magnetic stimulation as a refined brain mapping methodology. Krings, T., Chiappa, KH., Foltys, H., et al.[2019]

The study found that the 'standard' procedure for positioning TMS coils inaccurately targeted the dorsolateral premotor cortex (dlPMC) and dorsolateral prefrontal cortex (dlPFC) in many patients, with errors of about 1 to 2 cm, which could affect treatment outcomes.

Using a neuronavigation system that accounts for individual brain anatomy significantly improved the accuracy of targeting these regions, suggesting that more precise coil placement could enhance the efficacy of TMS treatments for depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of "standard" and "navigated" procedures of TMS coil positioning over motor, premotor and prefrontal targets in patients with chronic pain and depression. Ahdab, R., Ayache, SS., Brugières, P., et al.[2015]

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 (nTMS) was effectively used for preoperative functional mapping in 10 patients with rolandic tumors, showing reliable results that corresponded well with direct cortical stimulation, the current gold standard.

The average safety margin between the tumor and the nearest motor response was similar for both nTMS (7.9 mm) and direct cortical stimulation (6.6 mm), indicating that nTMS can be a precise tool for surgical planning in motor cortex tumor surgeries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Navigated transcranial magnetic stimulation for preoperative functional diagnostics in brain tumor surgery. Picht, T., Mularski, S., Kuehn, B., et al.[2022]

Navigated transcranial magnetic stimulation (nTMS) can be effectively integrated into neurosurgical workflows, as demonstrated by 7 years of experience, allowing for improved mapping of brain functions and surgical planning.

The use of standard software and devices in the integration process facilitates the adoption of nTMS data in clinical settings, ensuring that patient registration, appointment planning, and documentation are streamlined within existing hospital information systems.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Implementing Functional Preoperative Mapping in the Clinical Routine of a Neurosurgical Department: Technical Note. Sollmann, N., Meyer, B., Krieg, SM.[2022]

Navigated transcranial magnetic stimulation (nTMS) is a safe and well-tolerated procedure for pre-surgical motor and language mapping in a large cohort of 733 neurosurgical patients, with no reported seizures or serious adverse events.

While some patients experienced discomfort or pain during the procedure, particularly with repetitive stimulation (23.4% discomfort and 69.5% pain), the overall safety profile suggests nTMS could be beneficial for patients with brain lesions, including those with frequent seizures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of navigated TMS for preoperative mapping in neurosurgical patients. Tarapore, PE., Picht, T., Bulubas, L., 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12111610/

Repetitive Transcranial Magnetic Stimulation targeted with ... Their results indicate that neuronavigation offers higher targeting precision, potentially leading to more consistent treatment outcomes, though ...

2. brainhealthconsultants.com brainhealthconsultants.com/neuronavigation-rtms-precise-effective/

How Neuronavigation Makes rTMS More Precise and ... In a U.S. registry of the first 403 patients treated for major depressive disorder using Nextstim's SmartFocus nTMS system, 76.2% reported a ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11913841/

A naturalistic analysis of rTMS treatment outcomes for ... A 4–7-week course of rTMS significantly reduce symptoms of self-reported depression (42.5% response) and clinician-assessed depression (40.7% response).

4. sciencedirect.com sciencedirect.com/science/article/pii/S1388245724003766

Consensus review and considerations on TMS to treat ... TMS continues to demonstrate broad evidence for safety and efficacy in treating depression. Newer forms of TMS are faster and potentially more effective.

5. brainstimjrnl.com brainstimjrnl.com/article/S1935-861X(23)01736-9/fulltext

Parcel-guided TMS: virtual and online neuronavigation Abstract. Transcranial magnetic stimulation (TMS) is an FDA-approved treatment for treatment-resistant major depression (TRD).

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9094636/

Safety and recommendations for TMS use in healthy subjects ... Safety and recommendations for TMS use in healthy subjects and patient populations, with updates on training, ethical and regulatory issues: Expert Guidelines

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6688778/

Repetitive transcranial magnetic stimulation treatment for ... This opinion review summarizes current knowledge in the field and addresses the future direction of rTMS treatment in MDD.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT05598931

Development of Neuro-Navigated Transcranial Magnetic ... Subjects will undergo a single MRI session and will then participate in an on-line neuro-navigation session in which various TMS coil positions will be recorded ...

9. clinicaltrials.gov clinicaltrials.gov/study/NCT01829165

Brain Imaging of rTMS Treatment for Depression The overarching goal of this research program is to elucidate causal and directional neural network- level abnormalities in depression, and how they are ...

10. sciencedirect.com sciencedirect.com/science/article/pii/S0165178123004328

Real world efficacy and safety of various accelerated deep ... Accelerated Deep TMS protocols are found to be safe, effective therapeutic options for MDD. They offer treatment resistant patients a treatment option with a ...