CPT + rTMS for PTSD

Recruiting at 2 trial locations

Overseen by John Burruss, MD

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

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

Trial Summary

What is the purpose of this trial?

The purpose of this study is to examine the benefits of combining repetitive Transcranial Magnetic Stimulation (rTMS) coupled with Cognitive Processing Therapy (CPT) in treating combat-related Posttraumatic Stress Disorder (PTSD) symptoms. The study will also examine change in depression, psychosocial functioning, and neurophysiological (i.e., electroencephalography and magnetic resonance images) measures.

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.

What data supports the effectiveness of the treatment CPT + rTMS for PTSD?

Research suggests that repetitive transcranial magnetic stimulation (rTMS) can help reduce PTSD symptoms, especially when combined with therapies like Cognitive Processing Therapy (CPT). Studies have shown that rTMS is more effective than a placebo in reducing PTSD and depression severity, although more research is needed to confirm these findings. ^{1 2 3 4 5}

Is rTMS safe for humans?

Repetitive Transcranial Magnetic Stimulation (rTMS) has been studied for over two decades and is considered safe for treating depression, with safety guidelines established and updated over the years. It has been used in various conditions, including PTSD, with no substantial changes in safety guidelines, indicating its general safety in humans. ^{2 5 6 7 8}

How does the treatment CPT + rTMS for PTSD differ from other treatments for this condition?

CPT + rTMS for PTSD is unique because it combines Cognitive Processing Therapy (CPT), a type of talk therapy, with repetitive Transcranial Magnetic Stimulation (rTMS), which uses magnetic fields to stimulate nerve cells in the brain. This combination aims to enhance the effectiveness of therapy by potentially improving brain function related to PTSD symptoms, offering a novel approach compared to traditional therapies that do not include brain stimulation. ^{2 3 5 9 10}

Research Team

John Hart, Jr., MD

Principal Investigator

The University of Texas at Dallas

F. Andrew Kozel, MD

Principal Investigator

Florida State University, College of Medicine

John Burruss, MD

Principal Investigator

Metrocare Services of Dallas

Eligibility Criteria

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 cannot stop taking medication that increases my risk of seizures.

Trial Timeline

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)

Treatment Details

Interventions

• Active rTMS (Device)
• Cognitive Processing Therapy (Behavioral Intervention)
• Sham rTMS (Device)

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.

Participant Groups

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

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Advances in repetitive transcranial magnetic stimulation for posttraumatic stress disorder: A systematic review. [2021]

2. Denmark pubmed.ncbi.nlm.nih.gov

[Repetitive transcranial magnetic stimulation treatment for post-traumatic stress disorder]. [2018]

3. United States 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. [2012]

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

Exposure Therapy and Simultaneous Repetitive Transcranial Magnetic Stimulation: A Controlled Pilot Trial for the Treatment of Posttraumatic Stress Disorder. [2020]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Repetitive TMS to augment cognitive processing therapy in combat veterans of recent conflicts with PTSD: A randomized clinical trial. [2018]

6. England pubmed.ncbi.nlm.nih.gov

Impacts of rTMS on Refractory Depression and Comorbid PTSD Symptoms at a Military Treatment Facility. [2021]

7. Korea (South) pubmed.ncbi.nlm.nih.gov

Safety Review for Clinical Application of Repetitive Transcranial Magnetic Stimulation. [2023]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Prefrontal transcranial magnetic stimulation for depression in US military veterans - A naturalistic cohort study in the veterans health administration. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Bilateral sequential theta burst stimulation in depressed veterans with service related posttraumatic stress disorder: a feasibility study. [2022]

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

Repetitive transcranial magnetic stimulation treatment of comorbid posttraumatic stress disorder and major depression. [2006]