Brain Stimulation for PTSD

Overseen By Lily A Brown, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: University of Pennsylvania

Disqualifiers: Pregnancy, Seizure disorder, Claustrophobia, others

Compensation: Varies

Number of Visits: 4

Duration: 5 weeks

120 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment using brain stimulation to help people with PTSD, specifically targeting arousal symptoms like being easily startled. It compares the effects of a real brain stimulation technique, called continuous theta burst stimulation (cTBS), with a placebo version to assess its effectiveness. Participants must have PTSD and no metal implants. As an unphased trial, this study provides a unique opportunity to contribute to innovative research in PTSD treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it excludes those who have had recent medication changes in the past 8 weeks. This might mean you need to be stable on your current medications for at least 8 weeks before joining.

What prior data suggests that continuous theta burst stimulation is safe for PTSD patients?

Research has shown that continuous theta burst stimulation (cTBS) is generally well-tolerated by people with PTSD. In one study, a similar treatment called iTBS proved as effective as traditional high-frequency stimulation in reducing PTSD symptoms in military veterans. Most symptom improvements occurred early, offering promise for quick relief.

Another study found that a patient with both PTSD and depression experienced significant symptom improvement after receiving continuous TBS to a specific brain area. The study reported no major side effects, suggesting that the treatment is safe for many people.

Overall, research suggests that cTBS is safe and may help reduce PTSD symptoms. However, individual reactions can vary, so consulting healthcare professionals is important to determine its suitability. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about continuous theta burst stimulation (cTBS) for PTSD because it offers a novel approach by using non-invasive brain stimulation to target specific brain regions, like the intraparietal sulcus. Unlike traditional treatments such as psychotherapy and medications like SSRIs, which can take weeks to show effectiveness, cTBS has the potential to provide quicker relief. Moreover, this technique is distinct because it modulates brain activity directly, offering a different mechanism of action compared to the usual chemical-based therapies. This could lead to new therapeutic pathways for individuals with PTSD who do not respond well to current treatments.

What evidence suggests that continuous theta burst stimulation is effective for PTSD?

Research has shown that theta burst stimulation (TBS) can reduce PTSD symptoms. Studies have found that TBS is as effective as traditional high-frequency stimulation in alleviating PTSD symptoms and depression. TBS has particularly helped patients improve their social and work life. This brain stimulation also shows promise in treating depression, which often accompanies PTSD. In this trial, participants will receive either continuous theta burst stimulation (cTBS) or a sham version to assess its specific effects on PTSD arousal symptoms. Evidence from similar treatments supports the potential benefits of cTBS. ^{1 2 3 4 6}

Who Is on the Research Team?

Lily A Brown, PhD

Principal Investigator

University of Pennsylvania

Are You a Good Fit for This Trial?

This trial is for right-handed adults aged 18-60 with PTSD, as diagnosed by the DSM-5 criteria. Participants must not have any metal implants in their body.

Inclusion Criteria

No metal implants

Right-handed

I have been diagnosed with PTSD by a professional.

Exclusion Criteria

Any medical condition that increases risk for fMRI or cTBS

Claustrophobia

Non-English speaking

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive continuous theta burst stimulation (cTBS) to the intraparietal sulcus (IPS) and undergo extinction training to reduce arousal symptoms

5 weeks

Multiple visits including Days 4, 5, 34, and 35

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of startle response and subjective distress

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Continuous Theta Burst Stimulation
• Sham Continuous Theta Burst Stimulation

Trial Overview The study tests if a brain stimulation technique called Continuous Theta Burst Stimulation (cTBS) to the Intraparietal Sulcus can reduce arousal symptoms in PTSD patients compared to sham (fake) treatment.

How Is the Trial Designed?

Group I: Continuous theta burst stimulation to the intraparietal sulcus Experimental Treatment 1 Intervention

Continuous theta burst stimulation will be delivered to the individually targeted intraparietal sulcus site at 100% RMT.

Group II: Sham continuous theta burst stimulation Placebo Group 1 Intervention

We will use the coil's electric stimulation functionality that allows for the delivery of a brief electric pulse to the scalp simultaneous to the pulse to mimic actual stimulation.

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

Published Research Related to This Trial

Intermittent theta burst stimulation (iTBS) significantly reduced anger symptoms in veterans with chronic PTSD after just one week of treatment compared to sham stimulation, indicating its potential efficacy in managing anger associated with PTSD.

The reduction in anger was sustained for at least one month after the treatment, suggesting that iTBS may provide lasting benefits for emotional regulation in PTSD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Secondary Analysis on Effects of Theta Burst Transcranial Magnetic Stimulation to Reduce Anger in Veterans With Posttraumatic Stress Disorder. van 't Wout-Frank, M., Shea, MT., Sorensen, DO., et al.[2022]

Theta burst stimulation (TBS) is a promising technique for altering brain excitability, with a review of studies showing that adverse events were mostly mild and occurred in only 5% of subjects, indicating a generally safe profile.

Despite its safety, TBS carries a theoretical higher risk of seizures compared to other stimulation methods, necessitating cautious application and further research into its dosing parameters to better understand seizure risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of theta burst transcranial magnetic stimulation: a systematic review of the literature. Oberman, L., Edwards, D., Eldaief, M., et al.[2022]

In a randomized, double-blind trial involving 56 patients, intermittent theta burst stimulation (iTBS) over the dorsomedial prefrontal cortex showed a significant reduction in negative symptoms for patients with depression, but not for those with schizophrenia.

The treatment was generally safe and well-tolerated, with serious adverse events occurring only in the sham group, indicating that iTBS may be a promising intervention for depressive symptoms in certain patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dorsomedial prefrontal theta burst stimulation to treat anhedonia, avolition, and blunted affect in schizophrenia or depression - a randomized controlled trial. Bodén, R., Bengtsson, J., Thörnblom, E., et al.[2021]

Intermittent Theta Burst Stimulation (iTBS) was well-tolerated by eight Australian veterans with PTSD, with only mild to moderate side effects reported, such as cranial pain and headaches, which were manageable with analgesics.

Participants showed significant reductions in PTSD and depression symptoms after 20 sessions of iTBS, along with improvements in cognitive functions like working memory and processing speed, suggesting that iTBS could be a promising new treatment for veterans with PTSD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exploring Theta Burst Stimulation for Post-traumatic Stress Disorder in Australian Veterans-A Pilot Study. Nursey, J., Sbisa, A., Knight, H., et al.[2021]

Intermittent theta burst stimulation (iTBS) for PTSD was tested in a randomized controlled trial with 47 participants before treatment and 43 after, showing that EEG can effectively track changes in brain connectivity related to treatment response.

Using machine learning, the study found that EEG data could accurately distinguish between active and sham treatments with 75% accuracy, suggesting that EEG could be a practical tool for personalizing PTSD treatments based on brain activity patterns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changes in functional connectivity after theta-burst transcranial magnetic stimulation for post-traumatic stress disorder: a machine-learning study. Zandvakili, A., Swearingen, HR., Philip, NS.[2022]

Theta-burst stimulation (TBS) shows promise as a rapid and effective treatment for psychiatric disorders, particularly treatment-resistant depression and auditory hallucinations, with studies indicating mild adverse effects but no severe complications like seizures or mania.

The current research on TBS is varied in design and outcomes, highlighting the need for more rigorous sham-controlled studies to better assess its long-term safety and efficacy in treating various psychiatric conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Theta-Burst Stimulation in the Treatment of Psychiatric Disorders: A Review of the Literature. Rachid, F.[2019]

A study involving 50 veterans with PTSD showed that intermittent theta-burst stimulation (iTBS) significantly improved social and occupational functioning after 2 weeks, indicating its potential efficacy as a treatment for PTSD.

One month after treatment, iTBS demonstrated significant reductions in both clinician- and self-rated PTSD symptoms, as well as improvements in depression and functioning, suggesting that iTBS could be a promising new approach for managing PTSD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Theta-Burst Transcranial Magnetic Stimulation for Posttraumatic Stress Disorder. Philip, NS., Barredo, J., Aiken, E., et al.[2020]

Theta-burst Stimulation (TBS) is a promising form of repetitive transcranial magnetic stimulation that can induce significant and lasting changes in brain activity with lower intensity and shorter duration than traditional methods, making it a potentially more efficient treatment option.

TBS may have therapeutic implications for neuropsychiatric disorders due to its ability to promote synaptic plasticity, although the exact neurobiological mechanisms, including processes like long-term potentiation and GABAergic modulation, are still being researched.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mechanisms and applications of theta-burst rTMS on the human motor cortex. Cárdenas-Morales, L., Nowak, DA., Kammer, T., et al.[2009]

Continuous theta burst stimulation (cTBS) effectively inhibits synaptic transmission in the primary motor cortex for up to 1 hour, demonstrating its potential as a novel neuromodulation technique.

cTBS applied to the left motor cortex increases local GABA levels, indicating enhanced GABAergic activity, while not significantly affecting glutamate/glutamine levels, suggesting a specific mechanism of action for this stimulation technique.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurochemical effects of theta burst stimulation as assessed by magnetic resonance spectroscopy. Stagg, CJ., Wylezinska, M., Matthews, PM., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7162862/

One-year clinical outcomes following theta burst stimulation ... This study reviewed naturalistic outcomes up to 1-year from study endpoint, to test the hypothesis that greater exposure to active iTBS would be associated ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02769312?cond=theta&viewType=Table&checkSpell=&rank=7

Theta -Burst Neuromodulation for PTSD (TBS) Primary outcomes measures include a feasibility of TBS procedures, with secondary outcome measures focusing on changes in PTSD symptom severity and quality of ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6824981/

Theta Burst Transcranial Magnetic Stimulation for ... Intermittent theta-burst stimulation (iTBS) is a new, more rapid administration protocol with data supporting efficacy in depression.

4. sciencedirect.com sciencedirect.com/science/article/pii/S1094715923001356

Theta Burst Stimulation Is Not Inferior to High-Frequency ... Our data suggest that iTBS is similar to 10-Hz stimulation in inducing reductions in PTSD symptoms and depression in military veterans.

5. psychiatryonline.org psychiatryonline.org/doi/10.1176/appi.ajp.2019.18101160

Theta-Burst Transcranial Magnetic Stimulation for ... At 2 weeks, active stimulation improved social and occupational function and had indications of efficacy on depressive and self-reported PTSD ...

6. frontiersin.org frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2023.1061088/full

Accelerated theta-burst transcranial magnetic stimulation of ... We report a case of a 25-year-old woman with PTSD and depression whose symptoms markedly improved after continuous TBS of the right dorsolateral prefrontal ...