Targeted Plasticity Therapy for Posttraumatic Stress Disorder

Study Overview
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Brief Summary
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Posttraumatic stress disorder is a debilitating condition that develops in the aftermath of a traumatic experience, leading to hyperarousal, heightened anxiety, and uncontrolled fear that can be driven by intrusive memories or trauma reminders. The Texas Biomedical Device Center has developed a novel technique, termed targeted plasticity therapy (TPT), to boost neuroplasticity in conjunction with various forms of rehabilitation, including prolonged exposure therapy. The technique involves stimulation of the vagus nerve. The purpose of this open-label pilot study is to assess the safety of using a new device to deliver vagus nerve stimulation to reduce symptom severity in participants with PTSD when paired with prolonged exposure therapy. Additionally, the study will assess the prospective benefit of the system and garner an initial estimate of efficacy for a subsequent trial.

Official Title
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Targeted Plasticity Therapy for Posttraumatic Stress Disorder

Conditions
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Post Traumatic Stress Disorder

Intervention / Treatment
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* Device: Paired Vagus Nerve Stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Patients diagnosed with chronic PTSD for at least 3 months based on the DSM-5 criteria (PSSI-5 score of 9-45) Appropriate candidate for VNS implantation Adult, aged 18-64 Provision of signed and dated informed consent form Willingness to comply with all study procedures and availability for the duration of the study Right vocal cord has normal movement when assessed by laryngoscopy Women of reproductive potential must use contraceptive protection Exclusion Criteria PSSI-5 score of 46 or greater (very severe symptoms) Current substance dependence Currently undergoing prolonged exposure therapy elsewhere Concomitant clinically significant brain injuries Prior injury to vagus nerve Prior or current treatment with vagus nerve stimulation Participant receiving any therapy (medication or otherwise) that would interfere with VNS Planning to become pregnant, currently pregnant, or lactating Clinical complications that hinder or contraindicate the surgical procedure Cognitive impairment that would interfere with study participation, confirmed by medical evaluation (will be assessed through chart review and with the Cognistat) Psychological conditions such as schizophrenia, bipolar disorder, or psychosis that could interfere with study participation and follow-up Participation in other interventional clinical trial Participants with known immunodeficiency including participants who are receiving or have received chronic corticosteroids, immunosuppressants, immunostimulating agents or radiation therapy within 6 months Significant comorbidities or conditions associated with high risk for surgical or anesthetic survival (e.g. renal failure, unstable cardiac disease, poorly controlled diabetes, immunosuppression, etc.). Active neoplastic disease. Significant local circulatory problems that would interfere with device implantation and communication, (e.g. thrombophlebitis and lymphedema). Any condition which, in the judgment of the Investigator, would preclude adequate evaluation of device's safety and performance. Incarceration or legal detention Non-English speaking Patients who are acutely suicidal and/or have been admitted for a suicide attempt

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vagus Nerve Stimulation + Prolonged Exposure Therapy<br>Study treatment is vagus nerve stimulation (VNS) delivered during Prolonged Exposure Therapy. | Device: Paired Vagus Nerve Stimulation<br>* Stimulation of the vagus nerve that is paired with Prolonged Exposure Therapy.<br>* Other names: paired VNS;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Adverse Events [Device Safety] | Review of adverse events reported throughout the trial will be used to inform the potential risks associated with the ReStore system and provide a better understanding of risk/benefit analysis. | From Week 1 through study follow-up, approximately two years from the date of implant | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) | The CAPS-5 is a 30-item structured PTSD diagnostic interview that measures PTSD symptoms. (Weathers, Bovin, Lee, et al. 2018). | Weeks 1, 9, 15, 19, 36, 62 | 
| PTSD Checklist for DSM-5 (PCL-5) | The PCL-5 is a 20 item self-report measure that assesses the 20 DSM-5 symptoms of PTSD. (Weathers, Litz, Keane, et al. 2013). | Weeks 1, 9-15, 19, 36, 62 | 
| Patient Health Questionnaire-9 (PHQ-9) | The PHQ-9 is a brief self-report measure of major depressive disorder (Kroenke et al, 2001). The PHQ-9 is considered to be a valid measure of depression for population-based studies and clinical populations (Corson, Gerrity, & Dobscha, 2004) with a cut off score of equal or greater than 10 as the diagnostic for current depression. | Weeks 1, 9-15, 19, 36, 62 | 
| Generalized Anxiety Disorder 7-item Scale (GAD-7) | The GAD7 is a 7-item questionnaire that measures severity of anxiety (Spitzer et al, 2006). Response options are not at all, several days, more than half the days, and nearly every day, scored as 0, 1, 2, and 3, respectively. Therefore, GAD-7 scores range from 0 to 21, with scores of 5, 10, and 15 representing mild, moderate, and severe anxiety symptom levels, respectively. | Weeks 9, 15, 19, 36, 62 | 
| Posttraumatic Cognitions Inventory (PTCI) | The PTCI is a 36-item instrument that assesses dysfunctional post-trauma cognitions across self, world, and self-blame to yield a total score (Foa et al., 1999). The scale has high internal consistencies (.97, .88, .86, .97, respectively) and correlates well with PTSD severity, anxiety, and depression (.44 to .79). | Weeks 9-15, 19, 36, 62 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vagus Nerve Stimulation (VNS), Prolonged Exposure Therapy (PE), PTSD, Post Traumatic Stress Disorder