TMS for Anxiety Disorders

(ConTRA Trial)

Overseen By Emma Jones

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Brigham and Women's Hospital

Must not be taking: Rapid antidepressants

Disqualifiers: Pregnancy, TMS exposure, Bipolar, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 5

Duration: 1 week

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new approach called Connectomic Targeted TMS (Transcranial Magnetic Stimulation) to help individuals with anxiety disorders, such as panic disorder or PTSD, improve their symptoms. The study compares real TMS treatments to a placebo version to determine its effectiveness. Those who have tried medication or therapy without success and experience moderate anxiety may find this trial suitable. Participants will receive up to 50 sessions over five days and may switch to real treatment if they start with the placebo. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial requires that you stay on a stable psychiatric medication regimen for 4 weeks before and throughout the treatment. So, you should not stop taking your current medications if they are part of your stable regimen.

What prior data suggests that this TMS treatment is safe for anxiety disorders?

Research has shown that Connectomic Targeted TMS, a type of brain stimulation, is generally safe. A study on individuals with major depressive disorder (MDD) and anxiety found that participants tolerated it well. The side effects resembled those of other TMS treatments. Common side effects may include mild headaches or scalp discomfort, which are usually temporary. This suggests that Connectomic Targeted TMS could be safe for those with anxiety-related disorders. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for anxiety disorders?

Researchers are excited about Connectomic Targeted Transcranial Magnetic Stimulation (TMS) for anxiety disorders because it offers a novel approach by precisely targeting the brain's anxiosomatic pathways using neuronavigation. Unlike traditional treatments such as medication or talk therapy, which can take weeks to show effects, TMS can potentially provide quicker symptom relief. Additionally, this technique minimizes systemic side effects since it is non-invasive and directly focuses on specific brain regions. The use of aiTBS (accelerated intermittent Theta Burst Stimulation) further distinguishes it by enhancing the precision and personalization of the treatment, potentially leading to more effective outcomes for patients with anxiety disorders.

What evidence suggests that Connectomic Targeted TMS might be an effective treatment for anxiety disorders?

Research has shown that Connectomic Targeted TMS (Transcranial Magnetic Stimulation) may help treat anxiety disorders. Studies have found that this method can focus on specific brain areas related to anxiety, potentially reducing symptoms. In past trials, patients with both depression and anxiety experienced a noticeable decrease in anxiety after treatment. This trial will compare two groups: one receiving real aiTBS and another receiving sham aiTBS, both using neuronavigation to target treatment. This technique uses detailed brain mapping to tailor the treatment to each person, leading to better results. Overall, these early findings suggest that Connectomic Targeted TMS could effectively manage anxiety disorders. ^{1 2 3 6 7}

Who Is on the Research Team?

Shan Siddiqi, MD

Principal Investigator

Brigham and Women's Hospital

Are You a Good Fit for This Trial?

This trial is for individuals with anxiety-related disorders, such as panic disorder, generalized anxiety disorder, social anxiety disorder, obsessive-compulsive disorder, and PTSD. Participants will receive either real or sham TMS treatments over a short period.

Inclusion Criteria

My psychiatric medication has been stable for at least 4 weeks.

I have a mental health professional overseeing my care throughout the trial.

Agreement to abstaining from becoming pregnant from screening to two weeks after treatment (the MRI visit)

Exclusion Criteria

Active pregnancy as determined by a urine pregnancy test

I have a condition like autism that affects my ability to make decisions.

History of bipolar I disorder or schizophrenia

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 50 active or sham TMS treatments over 5 days

1 week

5 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Multiple visits (in-person and virtual)

Open-label crossover extension

Participants randomized to sham who do not respond will be offered an open-label crossover extension

What Are the Treatments Tested in This Trial?

Interventions

• Connectomic Targeted TMS

Trial Overview The study tests aiTBS (a form of TMS) targeting an anxiosomatic circuit against a sham treatment to see if it can reduce symptoms in patients with various anxiety disorders. The effectiveness will be measured using the BAI scale.

How Is the Trial Designed?

Group I: Real aiTBS Active Control 1 Intervention

Participants in this group will receive aiTBS with neuronavigation to the anxiosomatic treatment target.

Group II: Sham aiTBS Placebo Group 1 Intervention

Participants in this group will receive sham aiTBS with neuronavigation to the anxiosomatic treatment target.

Who Is Running the Clinical Trial?

Brigham and Women's Hospital

Lead Sponsor

Trials

1,694

Recruited

14,790,000+

Published Research Related to This Trial

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]

Inhibitory repetitive transcranial magnetic stimulation (rTMS) targeting the intraparietal sulcus (IPS) effectively reduced physiological arousal related to fear and anxiety during shock threat conditions, as evidenced by decreased startle responses in participants.

Although active rTMS did not show a difference in subjective anxiety ratings compared to sham stimulation, the findings suggest that modulating IPS excitability could be a promising approach for developing treatments for clinical anxiety disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-frequency parietal repetitive transcranial magnetic stimulation reduces fear and anxiety. Balderston, NL., Beydler, EM., Goodwin, M., et al.[2022]

In a study with 12 participants, slow repetitive transcranial magnetic stimulation (rTMS) applied to the right dorsolateral prefrontal cortex led to a significant increase in EEG theta activity in the left hemisphere, indicating a potential mechanism of action for mood improvement.

Participants experienced a notable decrease in anxiety immediately after rTMS and at 35 and 65 minutes post-treatment, suggesting that this non-invasive intervention may effectively reduce anxiety symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of slow rTMS at the right dorsolateral prefrontal cortex on EEG asymmetry and mood. Schutter, DJ., van Honk, J., d'Alfonso, AA., et al.[2019]

In a pilot study involving three patients with Panic Disorder who had not responded to other treatments, transcranial magnetic stimulation (TMS) showed only modest and partial symptom improvement after 10 sessions, which was not clinically significant.

An alternate TMS approach using both high and low frequency stimulation was well tolerated but did not lead to additional benefits, suggesting that while TMS is safe, its efficacy in treating Panic Disorder needs further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Panic disorder and transcranial magnetic stimulation]. García-Toro, M., Salva Coll, J., Crespí Font, M., et al.[2008]

In a study involving 429 pediatric patients undergoing transcranial magnetic stimulation (TMS) for motor and language mapping, most adverse events were benign, with seizures occurring in 5.8% of sessions but not conclusively linked to TMS.

TMS was safely performed in patients with cranial metal, and useful mapping results were achieved in nearly all cases, indicating that TMS is a safe option for functional mapping in pediatric patients with epilepsy or brain tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Image-guided TMS is safe in a predominately pediatric clinical population. Braden, AA., Weatherspoon, SE., Boardman, T., et al.[2022]

Mild adverse effects (MAEs) from transcranial magnetic stimulation (TMS) occur in about 5% of sessions, with most symptoms like headache and nausea reported after the sessions, particularly during initial treatments.

The study found no significant links between participant characteristics (age and gender) or TMS parameters (frequency and intensity) and the occurrence of MAEs, suggesting that initial participant anxiety may play a role in these reports.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative incidence rates of mild adverse effects to transcranial magnetic stimulation. Maizey, L., Allen, CP., Dervinis, M., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06376877

Connectomic Targeted TMS Target for Refractory Anxiety We prospectively tested this target in a sample of participants with major depressive disorder (MDD) with comorbid anxiety symptoms and found ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10175990/

An agile, data‐driven approach for target selection in rTMS ... We provide a proof of concept for an agile target selection paradigm based on using connectomic methods that can be used to detect patient‐specific abnormal ...

3. withpower.com withpower.com/trial/phase-2-psychiatric-disorders-7-2024-a1aa1

TMS for Anxiety Disorders (ConTRA Trial) The ConTRA medical study, being run by Brigham and Women's Hospital, needs participants to evaluate whether Connectomic Targeted TMS will have tolerable ...

4. ctv.veeva.com ctv.veeva.com/study/connectomic-targeted-tms-target-for-refractory-anxiety

Connectomic Targeted TMS Target for Refractory Anxiety We will perform a randomized sham-controlled trial of aiTBS to an anxiosomatic circuit in patients with anxiety-related disorders.

5. sciencedirect.com sciencedirect.com/science/article/pii/S2213158225001433

Treatment outcome is associated with pre- ... We associated pre-treatment network measures with treatment response by combining data from four clinical trials with pre- and post-treatment ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11575723/

Personalised transcranial magnetic stimulation for treatment ... Transcranial magnetic stimulation (TMS) is a promising intervention for treatment-resistant psychiatric disorders.

7. researchgate.net researchgate.net/publication/390072977_Evaluating_the_Safety_Profile_of_Connectome-Based_Repetitive_Transcranial_Magnetic_Stimulation

(PDF) Evaluating the Safety Profile of Connectome-Based ... Results suggested that individualized, connectome-guided rTMS is safe and contain side effect profiles similar to other TMS approaches reported ...