Responsive Neurostimulation for PTSD

Overseen By Sonja Hiller

Age: 18 - 65

Sex: Male

Travel: May Be Covered

Trial Phase: Phase < 1

Sponsor: VA Greater Los Angeles Healthcare System

Must be taking: Psychotropic medications

Must not be taking: Warfarin

Disqualifiers: Suicide attempt, Psychosis, Bipolar, Alcohol use, others

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

Compensation: Varies

Number of Visits: 3

Duration: 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore a new treatment for veterans with severe PTSD (post-traumatic stress disorder) that hasn't improved with other treatments. The study uses the NeuroPace RNS System, a device designed to detect brain signals linked to PTSD symptoms and respond with small electrical pulses to help reduce these symptoms. Ideal candidates for the trial are male veterans who have experienced chronic and treatment-resistant PTSD for at least five years, causing significant distress in their everyday lives.

As an Early Phase 1 trial, participants will be among the first to receive this innovative treatment, contributing to understanding its effects in people.

Will I have to stop taking my current medications?

Participants must be stable on their current psychotropic medication for 2 months before the trial and cannot increase dosages or add new medications for the first 6 months, unless medically necessary.

What prior data suggests that this device is safe for treating PTSD?

Research has shown that the NeuroPace RNS System is generally safe and well-tolerated. Data from a large study over nine years suggested that this type of brain stimulation remains safe over time. An early study on PTSD also showed promising safety results. Initial findings reported that stimulating the amygdala, a part of the brain involved in emotions, was safe. While these results are encouraging, it is important to remember that this treatment is still in the early stages of testing specifically for PTSD. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the NeuroPace® RNS® System for PTSD because it offers a novel approach by using responsive neurostimulation. Unlike traditional treatments for PTSD, which typically involve medications like SSRIs or therapies such as cognitive behavioral therapy, the RNS System directly targets brain activity. It is designed to detect and respond to abnormal electrical patterns, potentially providing more immediate and personalized relief from PTSD symptoms. This innovative method could be a game-changer for those who haven't found success with existing treatments.

What evidence suggests that the NeuroPace® RNS® System might be an effective treatment for PTSD?

Research has shown that responsive neurostimulation (RNS) might help reduce PTSD symptoms. In a study with patients unresponsive to other treatments, stimulating the basolateral amygdala (BLA) appeared to lessen trauma-related symptoms. This trial involves a single treatment arm where participants receive the RNS implant and undergo programming to optimize PTSD symptoms. The RNS device may interrupt fear signals in the brain, reducing fear responses. Early results from a small study also indicated that a PTSD patient felt better after BLA stimulation. While these findings are preliminary, they offer hope for using brain stimulation to manage PTSD symptoms. ^{1 2 5 6 7}

Are You a Good Fit for This Trial?

This trial is for male veterans aged 25-60 with severe PTSD that hasn't improved after trying at least three different treatments, including medication and psychotherapy. They must have stable health conditions, be on consistent psychotropic medications for two months prior to the study, and live in Southern California for the first year of the trial.

Inclusion Criteria

Have you responded poorly to previous treatments for post-traumatic stress disorder?

You have been diagnosed with Post-Traumatic Stress Disorder

Male aged 25-60 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Implantation and Initial Programming

Participants undergo the placement of the RNS implant and initial programming to optimize PTSD symptoms

4 weeks

1 visit (in-person)

Treatment

Responsive Neurostimulation is used to detect and treat PTSD symptoms by targeting electrophysiological biomarkers

12 months

Monthly visits (in-person) for the first year

Follow-up

Participants are monitored for safety and effectiveness after treatment using psychological scales, neuroimaging, and EEG

36 months

Quarterly visits (in-person) during years 2-4

What Are the Treatments Tested in This Trial?

Interventions

• NeuroPace® RNS® System

Trial Overview The NeuroPace® RNS® System is being tested to see if it can help manage PTSD by recording brain signals related to fear and stress from the amygdala. When certain patterns are detected, it sends out electrical pulses aimed at reducing symptoms like flashbacks and nightmares.

How Is the Trial Designed?

Group I: RNS group Experimental Treatment 1 Intervention

This study consists in only one arm. In this arm, the patients will undergo the placement of the RNS implant and the subsequent RNS programming to optimize the PTSD symptoms.

Who Is Running the Clinical Trial?

VA Greater Los Angeles Healthcare System

Lead Sponsor

Trials

53

Recruited

8,700+

University of California, Los Angeles

Collaborator

Trials

1,594

Recruited

10,430,000+

Published Research Related to This Trial

This Phase 1b trial involves 24 participants with PTSD, testing the NMDAR antagonist lanicemine for its safety, tolerability, and potential efficacy in reducing behavioral sensitization, which is linked to heightened anxiety and stress responses.

The study uniquely focuses on measuring the drug's engagement with NMDARs and its effects on anxiety-potentiated startle responses, rather than just symptom severity, which may provide a new approach for evaluating treatments in psychiatric disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Proof-of-Mechanism Study to Test Effects of the NMDA Receptor Antagonist Lanicemine on Behavioral Sensitization in Individuals With Symptoms of PTSD. Lijffijt, M., Green, CE., Balderston, N., et al.[2023]

The study involved 8 patients and demonstrated that using intraoperative computed tomography (iCT) during the implantation of the NeuroPace responsive neurostimulation (RNS) system allows for accurate targeting of leads, with a mean Euclidean distance error of only 2.63 mm.

Postoperative results showed a significant reduction in seizure frequency, from a median of 3.4 seizures per month preoperatively to 0.78 seizures per month, indicating the efficacy of the RNS system in managing seizures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Implantation of Responsive Neurostimulation for Epilepsy Using Intraoperative Computed Tomography: Technical Nuances and Accuracy Assessment. Kerolus, MG., Kochanski, RB., Rossi, M., et al.[2017]

Brain stimulation devices, including both traditional methods like Electroconvulsive Therapy (ECT) and newer techniques like Transcranial Magnetic Stimulation (TMS) and Vagus Nerve Stimulation (VNS), show promise in addressing PTSD symptoms, particularly in reducing associated anxiety and depression.

Current evidence suggests that while ECT may help with comorbid depression in PTSD patients, it does not significantly improve core PTSD symptoms, highlighting the need for more targeted research and novel treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brain stimulation in posttraumatic stress disorder. Novakovic, V., Sher, L., Lapidus, KA., et al.[2022]

The RNS® System offers a promising treatment for patients with refractory partial onset seizures, achieving a 44% reduction in seizures at one year, which improves to 60-66% over three to six years.

This closed-loop brain stimulation method does not negatively affect cognitive function or mood, and the risks associated with the device are comparable to those of other implanted medical devices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Responsive Direct Brain Stimulation for Epilepsy. Morrell, MJ., Halpern, C.[2022]

The NeuroPace RNS System can provide symptomatic relief for patients with drug-resistant partial seizures, but it carries significant risks of implant site infection and bone flap osteomyelitis, as seen in 3 reported cases.

In this study, 10% of patients developed infections related to the RNS device, particularly after multiple battery replacements, highlighting the need for improved techniques to minimize these risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Implant Site Infection and Bone Flap Osteomyelitis Associated with the NeuroPace Responsive Neurostimulation System. Wei, Z., Gordon, CR., Bergey, GK., et al.[2019]

A survey of 152 service members and veterans revealed that cranial electrotherapy stimulation (CES) led to clinical improvements of 25% or more in anxiety (66.7%), PTSD (62.5%), insomnia (65.3%), and depression (53.9%).

Participants overwhelmingly perceived CES as safe (99.0%), and those not on prescription medications found it more effective than when combined with medication, highlighting CES as a promising noninvasive treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Military service member and veteran self reports of efficacy of cranial electrotherapy stimulation for anxiety, posttraumatic stress disorder, insomnia, and depression. Kirsch, DL., Price, LR., Nichols, F., et al.[2015]

The study involved 12 Veterans with PTSD who underwent six sessions of virtual reality exposure combined with transcranial direct current stimulation (tDCS), targeting the ventromedial prefrontal cortex, showing that this combination can be applied without technical issues.

Results indicated that the tDCS combined with VR significantly reduced physiological arousal and led to a clinically meaningful decrease in PTSD symptoms, suggesting potential for this approach in future treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined transcranial direct current stimulation with virtual reality exposure for posttraumatic stress disorder: Feasibility and pilot results. van 't Wout-Frank, M., Shea, MT., Larson, VC., et al.[2021]

In a study involving 57 patients with medically refractory focal epilepsy, the Responsive Neurostimulation (RNS) System demonstrated a median reduction in seizure frequency of 60%, with 27% of patients achieving complete seizure freedom after a median follow-up of 23.1 months.

The surgical techniques described for implanting the RNS System were safe, with no infections or major complications reported, although some patients experienced lead fractures requiring exchanges.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Operative Technique and Lessons Learned From Surgical Implantation of the NeuroPace Responsive Neurostimulation® System in 57 Consecutive Patients. Krucoff, MO., Wozny, TA., Lee, AT., et al.[2021]

In a study involving 16 patients with medically refractory focal epilepsy, robotic-assisted implantation of the responsive neurostimulation system (RNS) led to an impressive average seizure reduction of 82% at 6 months and 90% at 1 year, demonstrating its efficacy as a treatment.

The use of the ROSA robot for targeting ictal-onset zones resulted in a highly accurate lead placement, with only a 0.165-mm discrepancy between the expected and actual lead locations, indicating a precise method for improving seizure control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Novel Robotic-Assisted Technique to Implant the Responsive Neurostimulation System. Tran, DK., Paff, M., Mnatsakanyan, L., et al.[2021]

Deep brain stimulation (DBS) has been explored as a treatment for PTSD, particularly in combat veterans, with promising results observed in animal models targeting specific brain areas like the medial prefrontal cortex and amygdala.

In clinical reports involving 3 patients, all showed varying degrees of improvement after receiving DBS, indicating potential efficacy, but the treatment remains investigational due to ethical concerns and challenges in recruitment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep Brain Stimulation for Post-Traumatic Stress Disorder: A Review of the Experimental and Clinical Literature. Meeres, J., Hariz, M.[2022]

Citations

1. reporter.nih.gov reporter.nih.gov/search/B6o0aSg12Eu8VsfeLO0wZA/project-details/10668215

Responsive Neurostimulation for Post-Traumatic Stress ... The present application proposes to investigate the use of Responsive Neurostimulation (RNS, Neuropace) in six (6) veterans suffering from severe treatment- ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1094715922012041

PO257 / #737 CLINICAL TRIAL OF RESPONSIVE ... PO257 / #737 CLINICAL TRIAL OF RESPONSIVE NEUROSTIMULATION OF THE AMYGDALA FOR TREATMENT-RESISTANT COMBAT POST-TRAUMATIC STRESS DISORDER: E-POSTER VIEWING.

3. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/282015

Responsive Neurostimulation for Post-Traumatic Stress ... In this intervention, patients suffering from PTSD undergo a surgical procedure to implant the responsive neurostimulation device (RNS, NeuroPace).

4. neuropace.com neuropace.com/wp-content/uploads/2021/02/neuropace-rns-system-clinical-summary.pdf

RNS System Clinical Summary This multi-center prospective clinical study conducted in the United States was designed to demonstrate adequate safety and evidence of effectiveness for the ...

5. neuromodulationjournal.org neuromodulationjournal.org/article/S1094-7159(22)01204-1/pdf

clinical trial of responsive neurostimulation of the amygdala ... Discussion: These preliminary data suggest that neurostimulation of the. BLA was safe and potentially effective for reducing trauma-related psychi- atric ...

6. neuropace.com neuropace.com/providers/rns-system-safety-data/

RNS System | Proven Safety Profile Responsive neurostimulation was well tolerated and safe over time. Conclusions from 9 years of data in the largest prospective neuromodulation study in the ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10209131/

A pilot study of closed-loop neuromodulation for treatment ... Neurostimulation has been proposed as a potential approach for treatment-resistant PTSD. Here in a pilot study the authors show that amygdala ...