CPT + rTMS for PTSD

Recruiting at 2 trial locations

Overseen By Gail Tillman, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: The University of Texas at Dallas

Must not be taking: Seizure-threshold lowering drugs

Disqualifiers: Epilepsy, Substance use, Psychotic disorder, others

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

Compensation: Varies

Number of Visits: 4

Duration: 12 weeks

330 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether combining two treatments—repetitive Transcranial Magnetic Stimulation (rTMS) and Cognitive Processing Therapy (CPT)—can better help veterans manage symptoms of combat-related Posttraumatic Stress Disorder (PTSD). rTMS uses magnetic fields to stimulate the brain, while CPT is a type of talk therapy. The trial also examines how these treatments affect depression and daily life functioning. Veterans who served in Post-9/11 military conflicts and have been diagnosed with combat-related PTSD might be suitable for this study. As an unphased trial, this study offers veterans the chance to contribute to innovative research that could improve PTSD treatments.

Will I have to stop taking my current medications?

The trial requires participants to stop taking any medication that significantly lowers the seizure threshold. If you are on such medications, you would need to discontinue them to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

A previous study demonstrated that repetitive Transcranial Magnetic Stimulation (rTMS) for treating PTSD is safe. Patients generally tolerate it well, experiencing only minor side effects. The FDA has approved TMS for other conditions, indicating its general safety. Similarly, research on Cognitive Processing Therapy (CPT) for PTSD has found it to be safe and effective, yielding positive results for patients. Both treatments have a history of safety, suggesting they are likely to be well-tolerated in studies like this one. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using repetitive transcranial magnetic stimulation (rTMS) for PTSD because it offers a unique approach compared to traditional treatments like medication and talk therapy. Most current options focus on altering brain chemistry or processing traumatic memories through conversation. However, rTMS uses magnetic fields to directly stimulate the brain, specifically targeting the right dorsolateral prefrontal cortex, which is involved in mood regulation and cognitive function. This approach could potentially offer faster symptom relief with fewer side effects. Additionally, combining rTMS with Cognitive Processing Therapy (CPT) might enhance the effectiveness of therapy sessions, providing a more comprehensive treatment option for PTSD.

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

Research has shown that Cognitive Processing Therapy (CPT), one of the treatments in this trial, reduces PTSD symptoms. Patients often experience a significant drop in symptom severity and maintain these improvements over time. In this trial, some participants will receive Active rTMS, which has shown promise in treating PTSD, especially when combined with other therapies. Recent studies suggest that using Active rTMS before CPT, as tested in this trial, leads to better symptom reduction than CPT alone. This combination may enhance the therapy's effectiveness, offering hope for those dealing with PTSD. ^{1 6 7 8 9}

Who Is on the Research Team?

John Burruss, MD

Principal Investigator

Metrocare Services of Dallas

F. Andrew Kozel, MD

Principal Investigator

Florida State University, College of Medicine

John Hart, Jr., MD

Principal Investigator

The University of Texas at Dallas

Are You a Good Fit for This Trial?

This trial is for post-9/11 veterans with combat-related PTSD. Participants must not have had recent trauma, high suicide risk, seizures, major head injuries, severe substance use in the past 3 months, certain brain conditions or metal implants near the head. Pregnant/nursing individuals and those on seizure-lowering meds are excluded.

Inclusion Criteria

You are a military veteran who served in conflicts after September 11, and you have been diagnosed with post-traumatic stress disorder (PTSD) specifically related to combat during that time.

Exclusion Criteria

I experienced a traumatic event within the last 3 months.

cardiac pacemaker, implanted medication pumps of any sort that would increase the risk of rTMS

I have a history of seizures.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 1 Hz rTMS to the rDLPFC prior to each of 12 Cognitive Processing Therapy (CPT) sessions or sham rTMS with CPT, or rTMS alone over 12 sessions

12 weeks

1 session per week

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments at 1-month, 6-months, and 12-months post-treatment

12 months

3 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Active rTMS
• Cognitive Processing Therapy
• Sham rTMS

Trial Overview

The study tests combining repetitive Transcranial Magnetic Stimulation (rTMS) with Cognitive Processing Therapy (CPT) to treat PTSD symptoms. It also looks at changes in depression levels, social functioning and brain activity through EEGs and MRIs.

How Is the Trial Designed?

Group I: Active rTMS Alone Active Control 1 Intervention

30 minutes of 1 Hz rTMS to rDLPFC at 1 session per week over 12 weeks

Group II: Active rTMS + CPT Active Control 2 Interventions

30 minutes of 1 Hz rTMS to rDLPFC prior to each CPT session

Group III: Sham rTMS + CPT Placebo Group 2 Interventions

30 minutes of sham repetitive transcranial magnetic stimulation (rTMS) to the right dorsolateral prefrontal cortex (rDLPFC) prior to each Cognitive Processing Therapy (CPT) session

Active rTMS is already approved in United States, European Union for the following indications:

Approved in United States as rTMS for:

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

Approved in European Union as rTMS for:

• Major Depressive Disorder (MDD)
• Obsessive-Compulsive Disorder (OCD)
• Chronic Pain Syndrome
• Generalized Anxiety Disorder (GAD)
• Bipolar Disorder

Who Is Running the Clinical Trial?

The University of Texas at Dallas

Lead Sponsor

Trials

71

Recruited

108,000+

Metrocare Services of Dallas

Collaborator

Trials

1

Recruited

330+

Johns Hopkins University

Collaborator

Trials

2,366

Recruited

15,160,000+

Florida State University

Collaborator

Trials

234

Recruited

41,100+

University of Texas Southwestern Medical Center

Collaborator

Trials

1,102

Recruited

1,077,000+

Published Research Related to This Trial

Bilateral sequential theta-burst stimulation (bsTBS) was well tolerated in a small study of 8 military veterans with treatment-resistant depression (TRD) and comorbid PTSD, showing promising remission rates of 25% and response rates of 38% for depression scores.

The study suggests that bsTBS may be a viable therapeutic option for patients with TRD and PTSD, indicating the need for larger studies to further evaluate its efficacy compared to other rTMS treatment paradigms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bilateral sequential theta burst stimulation in depressed veterans with service related posttraumatic stress disorder: a feasibility study. Vaithianathan, T., Blair, M., Soares, V., et al.[2022]

Repetitive transcranial magnetic stimulation (rTMS) is a safe treatment option for depression and shows potential for alleviating symptoms of post-traumatic stress disorder (PTSD), particularly when applied to the right dorsolateral prefrontal cortex.

High-frequency rTMS appears to be more effective than low-frequency rTMS in treating PTSD symptoms, possibly by increasing levels of brain-derived neurotrophic factor, which supports brain health and function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Repetitive transcranial magnetic stimulation treatment for post-traumatic stress disorder]. Jensen, BS., Ashkanian, M.[2018]

A study of 77 military patients receiving rTMS treatment showed significant reductions in depression and PTSD symptoms, with over 44% of patients experiencing a notable decrease in depression scores after treatment.

Most patients had previously tried multiple antidepressants (average of 2.7 trials), indicating that rTMS may be an effective alternative for those with treatment-resistant depression and comorbid PTSD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impacts of rTMS on Refractory Depression and Comorbid PTSD Symptoms at a Military Treatment Facility. Wilkes, S., Ona, C., Yang, M., et al.[2021]

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]

Repetitive transcranial magnetic stimulation (rTMS) was found to be significantly more effective than sham treatment in reducing PTSD symptoms and depression severity, with a standardized mean difference of -1.13 for PTSD and -0.83 for depression.

While high-frequency (HF) rTMS showed slightly better outcomes compared to low-frequency (LF) rTMS, the overall quality of evidence was rated very low due to factors like small sample sizes and inconsistent results, indicating a need for further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in repetitive transcranial magnetic stimulation for posttraumatic stress disorder: A systematic review. Belsher, BE., Beech, EH., Reddy, MK., et al.[2021]

In a study involving 103 veterans with combat-related PTSD, those who received repetitive Transcranial Magnetic Stimulation (rTMS) before Cognitive Processing Therapy (CPT) experienced significantly greater reductions in PTSD symptoms compared to those who received sham rTMS.

The benefits of combining rTMS with CPT were not only evident during treatment but also sustained for up to six months after the therapy, indicating a lasting impact on symptom relief.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive TMS to augment cognitive processing therapy in combat veterans of recent conflicts with PTSD: A randomized clinical trial. Kozel, FA., Motes, MA., Didehbani, N., et al.[2018]

In a study of 12 patients with both PTSD and major depression, 75% experienced a significant improvement in depression symptoms after receiving repetitive transcranial magnetic stimulation (rTMS) over 10 days.

While rTMS showed effectiveness in alleviating depression and related symptoms like anxiety and insomnia, it had only minimal impact on the core symptoms of PTSD, suggesting that different treatment approaches may be needed for mood and PTSD symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation treatment of comorbid posttraumatic stress disorder and major depression. Rosenberg, PB., Mehndiratta, RB., Mehndiratta, YP., et al.[2006]

In a study of 770 veterans with major depressive disorder (MDD), TMS treatment led to significant reductions in both MDD and PTSD symptoms, with a response rate of 41.4% and remission rate of 20% for MDD after receiving an adequate dose of 30 sessions.

The treatment was found to be safe, with side effects aligning with the known safety profile of TMS, and 65.3% of veterans with comorbid PTSD experienced clinically meaningful symptom reductions, indicating TMS's effectiveness in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prefrontal transcranial magnetic stimulation for depression in US military veterans - A naturalistic cohort study in the veterans health administration. Madore, MR., Kozel, FA., Williams, LM., et al.[2023]

In a case study of one Vietnam veteran with chronic PTSD, 20 minutes of repetitive transcranial magnetic stimulation (rTMS) at 1 Hz to the right prefrontal area significantly reduced the exaggerated P3a response to combat-related images, indicating a potential therapeutic effect.

The study provides electrophysiological evidence supporting the effectiveness of right frontal rTMS in alleviating hyperarousability to trauma-related stimuli, aligning with the patient's subjective reports of symptom improvement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation and threat memory: selective reduction of combat threat memory p300 response after right frontal-lobe stimulation. Tillman, GD., Kimbrell, TA., Calley, CS., et al.[2012]

This pilot study involving 8 veterans with PTSD shows that combining repetitive transcranial magnetic stimulation (rTMS) with prolonged exposure (PE) therapy is safe and feasible, with a dropout rate similar to traditional PE therapy.

While the overall improvement in PTSD symptoms was not statistically significant, veterans with comorbid major depression experienced notable benefits from rTMS, suggesting potential for enhanced treatment outcomes in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exposure Therapy and Simultaneous Repetitive Transcranial Magnetic Stimulation: A Controlled Pilot Trial for the Treatment of Posttraumatic Stress Disorder. Fryml, LD., Pelic, CG., Acierno, R., et al.[2020]

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