cTBS for PTSD

Recruiting at 1 trial location

Overseen By Michael Borich, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Emory University

Must not be taking: CNS active drugs, Psychoactive

Disqualifiers: Dementia, Head trauma, Substance abuse, others

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 2 days

66 Participants Needed

Trial Summary

Do I need to stop taking my current medications to join the trial?

Yes, you must stop taking any current psychoactive medications to participate in the trial.

What data supports the idea that cTBS for PTSD is an effective treatment?

The available research shows that continuous theta burst stimulation (cTBS) can be an effective treatment for PTSD. One study found that veterans who received more active sessions of a similar treatment, intermittent theta burst stimulation (iTBS), had better outcomes over a year compared to those who received fewer sessions. This suggests that cTBS, which is a variant of TMS, might also help reduce PTSD symptoms. While the research primarily focuses on iTBS, the positive results indicate that cTBS could be similarly beneficial. ^{1 2 3 4 5}

What safety data exists for cTBS treatment for PTSD?

The safety of theta burst stimulation (TBS), including continuous theta burst stimulation (cTBS), has been reviewed in the literature. A systematic review found that most adverse events were mild and occurred in about 5% of subjects. Although TBS has a theoretical risk of seizures due to high-frequency bursts, it is generally considered safe and efficacious. However, caution is advised due to its novelty, and there is a need for more rigorous documentation of adverse events and studies on seizure risk. Additionally, a comparative study on pediatric subjects suggests that the safety profile of TBS is still being evaluated. ^{1 2 6 7 8}

Is continuous theta burst stimulation (cTBS) a promising treatment for PTSD?

Yes, continuous theta burst stimulation (cTBS) is a promising treatment for PTSD. It is a new and faster form of transcranial magnetic stimulation (TMS) that can help reduce symptoms by affecting brain activity. This method has shown potential in treating PTSD and other conditions like depression and anxiety. ^{1 2 4 8 9}

What is the purpose of this trial?

This project represents a unique collaborative opportunity to pursue the essential proof-of-principle demonstration that non-invasive interference of sensory cortical memory consolidation shortly after an emotional experience can attenuate the cued fear response and potentially reduce the risk of developing post-traumatic stress disorder (PTSD). If successful, the study results would anchor a potential advance in the treatment of patients after a traumatic event and seed future animal and clinical studies of emotional sensory cortical memory consolidation to reduce the prevalence and negative sequelae of PTSD.

Research Team

Michael R Borich, PhD

Principal Investigator

Emory University

Eligibility Criteria

This trial is for adults who can consent and have been clinically diagnosed with PTSD. They should be willing to participate and not have musculoskeletal or neurological diseases. It's not for those with TMS or MRI contraindications, minors, pregnant women, prisoners, people outside the age range set by the study, those with dementia signs, on psychoactive meds recently, major head trauma survivors, neurodegenerative disorder patients or recent substance abusers.

Inclusion Criteria

Ability to provide informed consent

Willingness to participate in study

I have no history of muscle, bone, or nerve diseases.

Exclusion Criteria

Adults unable to consent, individuals who are not yet adults, pregnant women, and prisoners on scientific grounds and to minimize risk.

Participants that have a history of major head trauma, a neurodegenerative disorder, or recent (<6 months) substance abuse

I am within the specified age range for the trial.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo fMRI scans and are randomly assigned to receive either active or sham continuous theta burst stimulation (cTBS) to disrupt neural activity in the sensory cortex during the memory consolidation window.

2 days

2 visits (in-person)

Follow-up

Participants are monitored for changes in neural connections and physiological responses after treatment.

1 week

Treatment Details

Interventions

• Continuous theta burst stimulation (cTBS)
• Sham continuous theta burst stimulation (cTBS)

Trial Overview The trial tests if disrupting memory consolidation using non-invasive brain stimulation (cTBS) after a traumatic event can lessen fear responses and lower PTSD risk. Participants will receive either real cTBS or a sham (fake) treatment to compare effects on fear memories.

Participant Groups

Group I: cTBS: Inhibitory Transcranial magnetic stimulation (TMS) to sensory Cortex Experimental Treatment 1 Intervention

Participants will undergo a Functional magnetic resonance imaging (fMRI) scan while performing a fear conditioning/extinction task at the Center for Systems Imaging- Emory University Hospital (CSI-EUH) and then either stay at CSI-EUH or relocate to the Neural Plasticity Research Laboratory at Emory Rehabilitation Hospital. Participants will then be randomly assigned to either receive active or sham continuous theta burst stimulation (cTBS) to transiently disrupt neural activity in the targeted sensory cortex region specifically during the sensory memory consolidation window.

Group II: Sham cTBS Placebo Group 1 Intervention

Participants will undergo a Functional magnetic resonance imaging (fMRI) scan while performing a fear conditioning/extinction task at CSI-EUH and then either stay at CSI-EUH or relocate to the Neural Plasticity Research Laboratory at Emory Rehabilitation Hospital. Participants will then be randomly assigned to either receive active or sham continuous theta burst stimulation (cTBS) to transiently disrupt neural activity in the targeted sensory cortex region specifically during the sensory memory consolidation window.

Continuous theta burst stimulation (cTBS) is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Continuous theta burst stimulation for:

• Treatment-resistant depression
• Research for PTSD and anxiety disorders

Approved in European Union as Continuous theta burst stimulation for:

• Treatment-resistant depression
• Research for various neurological conditions

Approved in Canada as Continuous theta burst stimulation for:

• Treatment-resistant depression
• Research for neurological and psychiatric conditions

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

Findings from Research

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]

A study comparing intermittent theta burst stimulation (iTBS) and 5 Hz transcranial magnetic stimulation (TMS) in veterans with PTSD and major depressive disorder (MDD) found that both treatments were safe and effective, but 5 Hz TMS resulted in significantly better symptom improvement.

Veterans receiving 5 Hz TMS showed greater reductions in PTSD and MDD symptoms compared to those receiving iTBS, suggesting that while iTBS is quicker to administer, it may not be as effective for these conditions based on the current data from 20 participants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial Magnetic Stimulation for Posttraumatic Stress Disorder and Major Depression: Comparing Commonly Used Clinical Protocols. Philip, NS., Doherty, RA., Faucher, C., et al.[2022]

A 25-year-old woman with both PTSD and depression showed significant symptom improvement after receiving accelerated theta-burst stimulation (TBS) targeting the dorsolateral prefrontal cortex, suggesting this treatment may be effective for these conditions.

The results indicate that while accelerated TBS may lead to greater improvements in depression symptoms compared to PTSD symptoms, further research is needed to fully understand its safety and efficacy in patients with complex cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Accelerated theta-burst transcranial magnetic stimulation of the bilateral dorsolateral prefrontal cortex in a patient with post-traumatic stress disorder and major depressive disorder: Case report. Chang, CH., Liu, CY., Chen, SJ., et al.[2023]

The study found that continuous theta-burst stimulation (cTBS) can effectively reduce cortical excitability, but its effects show limited reproducibility across sessions, indicating variability in its impact.

Among the neurophysiological markers assessed, the modulation of corticospinal excitability measured 5 minutes after cTBS was the most consistent, suggesting it could be a reliable measure for future research on cTBS effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reproducibility of the effects of theta burst stimulation on motor cortical plasticity in healthy participants. Vernet, M., Bashir, S., Yoo, WK., et al.[2022]

In a study involving 46 veterans with PTSD, those who received 4 weeks of active intermittent theta burst stimulation (iTBS) had significantly better long-term outcomes, with a mean relapse time of 296 days compared to 182 days for those who received only 2 weeks of active treatment.

The study suggests that greater exposure to active iTBS is associated with reduced clinical relapse rates and that neuroimaging of brain connectivity may help predict long-term treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

One-year clinical outcomes following theta burst stimulation for post-traumatic stress disorder. Petrosino, NJ., Wout-Frank, MV'., Aiken, E., et al.[2021]

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 study of 165 pediatric participants aged 6 to 18, theta-burst TMS (TBS) demonstrated a similar safety profile to single- and paired-pulse TMS (sp/ppTMS), with no severe adverse effects reported.

The overall rate of adverse effects was 10.5% for TBS and 12.4% for sp/ppTMS, with most effects rated as minimal or mild, indicating that TBS is a safe option for further investigation in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of theta burst stimulation vs. single and paired pulse transcranial magnetic stimulation: a comparative study of 165 pediatric subjects. Hong, YH., Wu, SW., Pedapati, EV., et al.[2020]

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]

In a study involving 120 patients with generalized anxiety disorder, continuous theta burst stimulation (cTBS) showed greater efficacy than 1 Hz repetitive transcranial magnetic stimulation (rTMS) in reducing anxiety symptoms and increasing α oscillations after treatment and at a 1-month follow-up.

The increase in α frequency observed in the cTBS group correlated with improved psychological symptoms, suggesting that cTBS may enhance therapeutic effects through modulation of brain activity related to anxiety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical effects of continuous theta burst stimulation for generalized anxiety disorder and a mechanism involving α oscillations: a randomized controlled trial. Li, X., Zhang, C., Tan, J., et al.[2022]

References

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

Theta-Burst Transcranial Magnetic Stimulation for Posttraumatic Stress Disorder. [2020]

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

Transcranial Magnetic Stimulation for Posttraumatic Stress Disorder and Major Depression: Comparing Commonly Used Clinical Protocols. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Accelerated theta-burst transcranial magnetic stimulation of the bilateral dorsolateral prefrontal cortex in a patient with post-traumatic stress disorder and major depressive disorder: Case report. [2023]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Reproducibility of the effects of theta burst stimulation on motor cortical plasticity in healthy participants. [2022]

5. England pubmed.ncbi.nlm.nih.gov

One-year clinical outcomes following theta burst stimulation for post-traumatic stress disorder. [2021]

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

Safety of theta burst transcranial magnetic stimulation: a systematic review of the literature. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Safety and tolerability of theta burst stimulation vs. single and paired pulse transcranial magnetic stimulation: a comparative study of 165 pediatric subjects. [2020]

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

Neurochemical effects of theta burst stimulation as assessed by magnetic resonance spectroscopy. [2022]

9. Canada pubmed.ncbi.nlm.nih.gov

Clinical effects of continuous theta burst stimulation for generalized anxiety disorder and a mechanism involving α oscillations: a randomized controlled trial. [2022]