rTMS for Neurological Symptoms

(SET Trial)

Overseen By Neha Goyal

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Neuronetics

Disqualifiers: Head trauma, Neurologic disease, Drug abuse, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called repetitive Transcranial Magnetic Stimulation (rTMS) to assess its effects on neurological symptoms. The goal is to evaluate how rTMS might assist with certain brain-related conditions. Suitable candidates for this trial include adults who have trouble sleeping and are on stable medication for psychiatric or sleep-related issues. Participants should not have a history of head trauma or any metal implants near the head. As an unphased trial, this study provides a unique opportunity to contribute to groundbreaking research and potentially benefit from an innovative treatment approach.

Will I have to stop taking my current medications?

The trial requires that if you are on psychiatric or sleep medications, your dose must be stable for two weeks before joining and stay the same during the trial. For other medications, like hormonal therapy, your dose should also be stable. So, you won't have to stop taking them, but you can't change the dose.

What prior data suggests that this technique is safe for neurological symptoms?

A previous study found repetitive transcranial magnetic stimulation (rTMS) to be generally safe and well-tolerated for treating various conditions. Research shows that rTMS did not cause new symptoms and was easy for participants to handle. However, systolic blood pressure (the top number in a blood pressure reading) temporarily increased right after treatment.

Expert guidelines confirm that rTMS is usually safe for both healthy individuals and those with certain health conditions. Since the FDA has approved rTMS for treating major depression, evidence strongly supports its safety for use in humans. Overall, the treatment has a good safety record with few reported side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Repetitive Transcranial Magnetic Stimulation (rTMS) is unique because it uses magnetic fields to non-invasively stimulate nerve cells in the brain. Unlike traditional treatments for neurological symptoms, which often involve medication or more invasive procedures, rTMS offers a non-drug approach with fewer side effects. Researchers are excited about rTMS because it targets specific brain areas directly, potentially leading to quicker and more targeted symptom relief. This method opens up new possibilities for treating neurological conditions by harnessing the brain's own ability to change and adapt.

What evidence suggests that repetitive transcranial magnetic stimulation is effective for neurological symptoms?

Research has shown that repetitive transcranial magnetic stimulation (rTMS) can help treat various mental and brain-related conditions. Studies have found that rTMS uses magnetic fields to activate nerve cells in the brain, improving symptoms of major depression. For individuals whose depression hasn't improved with other treatments, rTMS has proven as effective as traditional options like lithium in preventing relapse. Additionally, combined results from multiple studies suggest that rTMS can reduce depression and anxiety symptoms in people with neurological disorders. Overall, rTMS is considered a safe and non-invasive treatment option. ^{1 6 7 8 9}

Who Is on the Research Team?

Steve Erickson

Principal Investigator

Neuronetics

Are You a Good Fit for This Trial?

This trial is for adults aged 22-70 with sleep issues, scoring >=8 on the ISI scale. Participants must be on a stable medication dose if they're taking psychiatric or sleep meds and use birth control if applicable. Excluded are those with TMS/MRI complications, certain mental health scores, hearing problems, implanted devices near the head, recent drug/device trials participation, metallic implants in the head, substance abuse issues, significant loss of consciousness history or diagnosed neurological diseases.

Inclusion Criteria

Voluntarily provides written informed consent and agree to comply with study procedures, including attending all study visits and completing all study assessments.

I am on a stable dose of medication for conditions like menopause.

Score > or = 8 on ISI scale

Exclusion Criteria

Subjects with any prior TMS or MRI complications, or any other issues/circumstance which, in the opinion of the investigator, might interfere with safety, study participation, or which might confound data interpretation.

PHQ-9 total score > or = 10 or QIDS total score > or = 11.

I have a history of fainting, hearing issues, or tinnitus.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive rTMS treatment and are assessed for changes in symptoms

4 weeks

Follow-up

Participants are monitored for durability of symptom changes and safety outcomes

16 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Repetitive Transcranial Magnetic Stimulation

Trial Overview The study is testing repetitive transcranial magnetic stimulation (rTMS) to see how it affects neurological symptoms. It's a forward-looking study where participants will undergo rTMS sessions and have their symptoms evaluated afterward to assess effectiveness and safety.

How Is the Trial Designed?

Group I: Open Label Experimental Treatment 1 Intervention

Single Group

Repetitive Transcranial Magnetic Stimulation 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

Approved in European Union as rTMS for:

• Major depressive disorder
• Obsessive-compulsive disorder
• Anxiety disorders

Approved in Canada as rTMS for:

• Major depressive disorder
• Obsessive-compulsive disorder

Who Is Running the Clinical Trial?

Neuronetics

Lead Sponsor

Trials

25

Recruited

15,300+

Published Research Related to This Trial

Repetitive transcranial magnetic stimulation (rTMS) has shown the ability to modify cortical activity, suggesting potential therapeutic benefits for various neurological conditions.

However, the rationale for using rTMS in many of these conditions remains unclear, indicating a need for further research to understand its effects and the underlying pathological processes involved.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is there a future for therapeutic use of transcranial magnetic stimulation? Ridding, MC., Rothwell, JC.[2022]

Low intensity repetitive magnetic stimulation (LI-rMS) can have different effects on neuron survival and morphology depending on the stimulation frequency, with simple pulse trains (10 Hz and 100 Hz) impairing cell survival, while more complex patterns do not.

LI-rMS increases intracellular calcium levels by releasing it from neuronal stores rather than from outside the cell, leading to changes in gene expression related to cell survival and neurite outgrowth, which helps explain the therapeutic effects observed in rTMS treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cellular and molecular changes to cortical neurons following low intensity repetitive magnetic stimulation at different frequencies. Grehl, S., Viola, HM., Fuller-Carter, PI., et al.[2018]

Repetitive transcranial magnetic stimulation (rTMS) is emerging as a safe and tolerable treatment option for various pediatric neurological disorders, showing therapeutic benefits in conditions like adolescent depression and hemiparesis from pediatric stroke.

While rTMS has shown promise in some areas, such as autism and tics/Tourette syndrome, more high-quality studies are needed, especially for conditions like migraine in children, where evidence is still lacking.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial Magnetic Stimulation for the Treatment of Pediatric Neurological Disorders. Malone, LA., Sun, LR.[2020]

Repetitive transcranial magnetic stimulation (rTMS) is an effective method for modulating brain activity and has been applied in treating a variety of neurological and psychiatric disorders, including stroke, Parkinson's disease, depression, and anxiety.

The review provides a comprehensive overview of rTMS protocols and offers evidence-based recommendations for their clinical use, highlighting its potential as a versatile treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Repetitive transcranial magnetic stimulation in neurology and psychiatry]. Chervyakov, AV., Poydasheva, AG., Korzhova, JE., et al.[2018]

In a study involving Sprague-Dawley rats, 15 days of low-frequency rTMS (0.5 Hz) significantly altered structural synaptic plasticity, indicating its potential therapeutic effects on neurological conditions.

The treatment increased the expression of key synaptic protein markers, such as synaptophysin and CaMKII, suggesting that rTMS may enhance synaptic function through these molecular changes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation (rTMS) modulates hippocampal structural synaptic plasticity in rats. Li, Y., Li, L., Pan, W.[2019]

Repetitive transcranial magnetic stimulation (rTMS) is a powerful tool that can effectively treat clinical depression and potentially other brain disorders, but it carries risks, including the potential to induce seizures, as evidenced by 7 known cases by 1996.

A workshop established safety guidelines for rTMS, emphasizing the importance of monitoring, ethical considerations, and the expertise required for its administration to minimize risks and enhance therapeutic outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk and safety of repetitive transcranial magnetic stimulation: report and suggested guidelines from the International Workshop on the Safety of Repetitive Transcranial Magnetic Stimulation, June 5-7, 1996. Wassermann, EM.[2022]

Repetitive transcranial magnetic stimulation (rTMS) has not been thoroughly studied for side effects, with the main known risk being the acute production of seizures.

While tissue damage from rTMS is unlikely, there are concerns about potential cognitive effects and the possibility of long-term changes in brain function that have not yet been fully understood.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Side effects of repetitive transcranial magnetic stimulation. Wassermann, EM.[2005]

Repetitive transcranial magnetic stimulation (rTMS) is generally safe for older adults with late-life depression, with only 12.4% reporting any adverse events and serious adverse events occurring in just 1.5% of cases, based on a review of 11 studies involving 353 patients.

The most common adverse events were mild, such as headaches (6.9%) and discomfort at the stimulation site (2.7%), although some serious adverse events, including psychiatric hospitalization and increased suicidal ideation, were noted in case reports, highlighting the need for further research to ensure safety in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events of repetitive transcranial magnetic stimulation in older adults with depression, a systematic review of the literature. Overvliet, GM., Jansen, RAC., van Balkom, AJLM., et al.[2021]

Repetitive transcranial magnetic stimulation (rTMS) shows promising therapeutic efficacy, particularly in relieving chronic pain and aiding motor neurorehabilitation in stroke patients, based on a review of 32 randomized controlled trials.

While rTMS may also improve motor function in Parkinson's disease and reduce seizure frequency in epilepsy, the evidence is less robust and requires further long-term studies to confirm these effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation in neurology: what we have learned from randomized controlled studies. Hemond, CC., Fregni, F.[2022]

Repetitive transcranial magnetic stimulation (rTMS) is a safe and effective non-invasive treatment for depression, with a low seizure risk of less than 0.1%.

Common side effects like headache and discomfort typically decrease with continued treatment, highlighting the importance of monitoring patient safety and medication interactions during rTMS sessions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical Application and Safety of rTMS in Japan and Overseas]. Kito, S.[2015]

Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for drug-resistant depression and has potential applications in various psychiatric and neurological disorders, including OCD, schizophrenia, and Alzheimer's disease.

rTMS works by generating an electromagnetic field that penetrates the scalp to stimulate brain neurons, potentially enhancing neurotransmitter activity and promoting neuroprotective effects, while also showing brain changes similar to those from electric shock therapy without causing seizures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Evaluation of repetitive transcranial magnetic stimulation effectiveness in treatment of psychiatric and neurologic diseases]. Pastuszak, Ż., Stępień, A., Piusińska-Macoch, R., et al.[2016]

In a study involving 62 patients with treatment-resistant depression, rTMS showed a response rate of 29.4% and a remission rate of 5.9% over 6 weeks, indicating its potential effectiveness in clinical practice.

The study found that early life stress may predict a better response to rTMS therapy, although the overall remission rates were lower compared to other recent studies, suggesting the need for further research to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A naturalistic, multi-site study of repetitive transcranial magnetic stimulation therapy for depression. Taylor, SF., Bhati, MT., Dubin, MJ., et al.[2019]

Repetitive transcranial magnetic stimulation (rTMS) has gained popularity for its ability to modulate brain activity, but safety considerations are crucial, especially with the recent updates to safety guidelines published in 2021.

The guidelines emphasize the importance of screening for risks, monitoring for adverse events, and specific safety measures when using rTMS, particularly in patients with conditions like stroke and traumatic brain injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Review for Clinical Application of Repetitive Transcranial Magnetic Stimulation. Kim, WS., Paik, NJ.[2023]

Citations

1. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK568715/

Repetitive Transcranial Magnetic Stimulation - StatPearls - NCBI Repetitive transcranial magnetic stimulation (rTMS) is a safe and non-invasive treatment technique used to treat various psychiatric and neurological disorders.

2. mayoclinic.org mayoclinic.org/tests-procedures/transcranial-magnetic-stimulation/about/pac-20384625

Transcranial magnetic stimulation Transcranial magnetic stimulation (TMS) is a procedure that uses magnetic fields to stimulate nerve cells in the brain to improve symptoms of major depression.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12273377/

Efficacy of repetitive transcranial magnetic stimulation in ... Our combined results indicate that rTMS can improve depressive and anxiety symptoms in ND patients. Notably, there were no significant ...

4. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2835319

Repetitive Transcranial Magnetic Stimulation as ... This randomized clinical trial of 75 participants with TRD showed that rTMS and lithium had comparable efficacy in preventing TRD relapse.

5. sciencedirect.com sciencedirect.com/science/article/pii/S1935861X24001128

Treatment expectations and clinical outcomes following ... Positive pre-treatment expectancy boosts remission odds in Treatment-Resistant Depression (TRD) after acute rTMS.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3656498/

Safety and tolerability of repetitive transcranial magnetic ... The published data suggest rTMS for the treatment or diagnosis of pathologic positive sensory phenomena appears to be a relatively safe and well-tolerated ...

7. fda.gov fda.gov/medical-devices/guidance-documents-medical-devices-and-radiation-emitting-products/repetitive-transcranial-magnetic-stimulation-rtms-systems-class-ii-special-controls-guidance

Repetitive Transcranial Magnetic Stimulation (rTMS) Systems This guidance document was developed as a special controls guidance to support the classification of Repetitive Transcranial Magnetic Stimulation (r TMS) ...

8. 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

9. ahajournals.org ahajournals.org/doi/10.1161/strokeaha.108.522144

Safety and Behavioral Effects of High-Frequency Repetitive ... In terms of safety, rTMS was well tolerated and did not cause new symptoms; systolic blood pressure increased from pre- to immediately post-rTMS ...