PTSD, Post Traumatic Stress Disorder
Conditions
Keywords
PTSD, Post-Traumatic Stress Disorder, VNS, Vagus Nerve Stimulation, TPT, Targeted Plasticity Therapy, ReStore System, PE, Prolonged Exposure Therapy, Trauma and Stressor Related Disorders, Mental Disorders, Stress Disorders, Traumatic, Stress Disorders, Post-Traumatic
Brief summary
Objectives of this study are to provide continued safety assessment for the ReStore system, and to gain further estimates of the effect size of Vagus Nerve Stimulation (VNS) therapy with Prolonged Exposure Therapy (PE) compared to PE with placebo (sham) stimulation in participants with posttraumatic stress disorder (PTSD)
Detailed description
A prospective, multi-center, randomized, controlled, blinded trial of participants implanted with the ReStore Device for VNS Therapy. In double-blinded Phase 1, after implantation, participants will be randomized to either active VNS stimulation or sham VNS stimulation, accompanying PE therapy twice weekly for 7 weeks (12 in-office sessions, Phase 1). The therapist and the participant will be blinded of the group assignment. Following completion of Phase 1, all participants undergo two mid-therapy assessments and then advance to the open-label Phase 2. In open-label Phase 2, all participants will receive up to an additional 12 sessions of PE therapy paired with active VNS stimulation, regardless of their prior assignment in Phase 1. Post-therapy assessments will be performed 1 day, 1 month, and 6 months following the completion of the final session of PE in Phase 2. During the in-office sessions, the therapist will use a secure smart device to deliver stimulation and record audio of the session for use during homework sessions. The smart device will automatically trigger VNS during audio homework sessions at the same times that the therapist delivered VNS during the corresponding in-office session. Long-term assessment of safety will be performed up to four times annually for up to 2 years following the date of implant or until the device is FDA approved when possible. Safety assessment will only report on the presence of the implanted, non-active device and/or participant status during this period. Participants who experience a serious device-related adverse event will be removed from the identified risk but will continue to be monitored for 2 years or longer if the event has not resolved.
Interventions
DEVICEActive VNS stimulation
The subjects in this group will be implanted with the ReStore device and receive active Vagus nerve stimulation (VNS) in phase 1
DEVICESham VNS stimulation
The subjects in this group will be implanted with the ReStore device and receive sham Vagus nerve stimulation (VNS) in phase 1
Sponsors
The University of Texas at Dallas
Congressionally Directed Medical Research Programs
The University of Texas Health Science Center at San Antonio
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
All are blinded in the RCT (Randomized Controlled Trial) phase. However, sites will need to have an unblinded programmer who is only programming the device and not collecting outcomes data
Intervention model description
1:1 randomization of active stimulation vs. sham stimulation for 12 sessions post randomization, followed by up to 12 sessions of open label active stimulation for all participants
Eligibility
Sex/Gender
ALL
Age
22 Years to 79 Years
Healthy volunteers
No
Inclusion criteria
1. Diagnosis of chronic PTSD for at least 3 months based on DSM-5 criteria 2. In the medical opinion of the Principal Investigator (PI), failed at least one adequate course of first-line PTSD treatment per American Psychological Association (APA) guidelines 3. PCL-5 score greater than 33 4. Age 22-79 years 5. Appropriate surgical candidate for VNS device implantation 6. Willing and able to comply with study protocol 7. Able to provide informed consent.
Exclusion criteria
1. Currently undergoing prolonged exposure therapy elsewhere 2. Concurrent participation in another interventional clinical trial 3. Prior injury to vagus nerve 4. Prior or current treatment with vagus nerve stimulation 5. Psychiatric disorders and/or cognitive impairments that would interfere with study participation, as assessed by medical evaluation 6. Moderate-High Risk of Suicide according to Columbia - Suicide Severity Rating Scale (C-SSRS) Screen Version 7. Persons with a current or past: (a) medical (psychiatric, non-psychiatric) condition, disease, disorder, injury, or disability or (b) non-medical situation or circumstance that, in the opinion of the principal investigator, study participation: * may pose a significant or undue risk to the person, * make it unlikely the person will complete all the study requirements per protocol, or * may adversely impact the integrity of the data or the validity of the study results 8. Persons with a neck circumference larger than 18.5 inches 9. Females of childbearing potential who are either pregnant or planning to become pregnant and who are not using, or will not agree to use medically acceptable birth control methods 10. Non-English speaking 11. As determined by the principal investigator, is under current incarceration or legal detention
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| ReStore System Safety | From surgery to up to 2 years following implantation or until the device is FDA approved, whichever comes first | ReStore System safety by review of any adverse events |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinician Administered PTSD Scale for DSM-5(fifth edition of the Diagnostic and Statistical Manual of Mental Disorders)(CAPS-5) | From baseline up to visit 33 (end of study) | The CAPS-5 is a 30-item structured PTSD diagnostic interview that measures PTSD. Total scores range from 0-80, with higher scores indicating more severe PTSD symptoms symptoms. |
| PTSD Checklist for DSM-5 (PCL-5) score | From baseline up to visit 33 (end of study) | The PCL-5 is a 20 item self-report measure that assesses the 20 DSM-5 symptoms of PTSD. Total scores range from 0-80, with higher scores indicating more severe PTSD symptoms symptoms. |
| PostTraumatic Cognitions Inventory (PTCI) | From baseline up to visit 33 (end of study) | The PTCI is a 33-item instrument that assesses dysfunctional post-trauma cognitions across self, world, and self-blame to yield a total score. Total scores range from 33-231, with higher scores reflecting greater endorsement of negative posttraumatic cognitions. |
| Generalized Anxiety Disorder 7-item Scale (GAD-7) | From baseline up to visit 33 (end of study) | The GAD-7 is a 7-item questionnaire that measures severity of anxiety. Total scores range from 0-21, with higher scores reflecting severe anxiety symptom levels. |
| Patient Health Questionnaire-9 (PHQ-9) | From baseline up to visit 33 (end of study) | The PHQ-9 is a brief self-report measure of major depressive disorder. Total scores range from 0-27, with higher scores reflecting severe depression symptom levels. |
Countries
United States
Contacts
CONTACTAmy Porter
CONTACTKatharine Dlouhy
PRINCIPAL_INVESTIGATORJane Wigginton, MD
The University of Texas at Dallas
PRINCIPAL_INVESTIGATORRobert Rennaker, PhD
The University of Texas at Dallas
PRINCIPAL_INVESTIGATORJasper Smits, PhD
The University of Texas at Austin
PRINCIPAL_INVESTIGATORMichael Foreman, MD
Baylor Scott and White Health
PRINCIPAL_INVESTIGATORMichael Kilgard, PhD
The University of Texas at Dallas
Outcome results
None listed