Targeted Plasticity Therapy for PTSD

Targeted Plasticity Therapy for the Treatment of Post-Traumatic Stress Disorder

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)

Study Overview

• Status: Recruiting
• Conditions: PTSD, Post Traumatic Stress Disorder
• Intervention / Treatment: Device: Active VNS stimulation; Device: Sham VNS stimulation

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.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Amy Porter; Phone Number: 972-883-7256; Email: alp160730@utdallas.edu
• Study Contact Backup: Name: Katharine Dlouhy; Phone Number: 972-883-7231; Email: katharine.dlouhy@utdallas.edu

Study Locations

• United States
  • Texas
    • Austin, Texas, United States, 78712
      • Recruiting
      • The University of Texas Health Austin Ambulatory Surgery Center
    • Dallas, Texas, United States, 75246
      • Recruiting
      • Baylor University Medical Center
      • Contact: Phone Number: (214) 865-2416
    • Richardson, Texas, United States, 75080
      • Recruiting
      • Texas Biomedical Device Center
      • Contact: Amy Porter; Phone Number: 972-883-7256

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Immediate VNS Group; The participants in this arm will be implanted with the device and will receive active VNS stimulations in phase 1 as well as phase 2 of the study.	Device: Active VNS stimulation; The subjects in this group will be implanted with the ReStore device and receive active Vagus nerve stimulation (VNS) in phase 1
Sham Comparator: Delayed VNS Group; The participants in this arm will be implanted with the device but will receive sham VNS stimulations in phase 1 of the study and active VNS in phase 2 of the study.	Device: Sham VNS stimulation; The subjects in this group will be implanted with the ReStore device and receive sham Vagus nerve stimulation (VNS) in phase 1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ReStore System Safety	ReStore System safety by review of any adverse events	From surgery to up to 2 years following implantation or until the device is FDA approved, whichever comes first

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinician Administered PTSD Scale for DSM-5(fifth edition of the Diagnostic and Statistical Manual of Mental Disorders)(CAPS-5)	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.	From baseline up to visit 33 (end of study)
PTSD Checklist for DSM-5 (PCL-5) score	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.	From baseline up to visit 33 (end of study)
PostTraumatic Cognitions Inventory (PTCI)	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.	From baseline up to visit 33 (end of study)
Generalized Anxiety Disorder 7-item Scale (GAD-7)	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.	From baseline up to visit 33 (end of study)
Patient Health Questionnaire-9 (PHQ-9)	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.	From baseline up to visit 33 (end of study)

Collaborators and Investigators

• Sponsor: The University of Texas at Dallas
• Collaborators: The University of Texas Health Science Center at San Antonio; Congressionally Directed Medical Research Programs
• Investigators: Principal Investigator: Jasper Smits, PhD, The University of Texas at Austin; Principal Investigator: Jane Wigginton, MD, The University of Texas at Dallas; Principal Investigator: Robert Rennaker, PhD, The University of Texas at Dallas; Principal Investigator: Mark Powers, PhD, Baylor Scott & White; Principal Investigator: Michael Kilgard, PhD, The University of Texas at Dallas

Study record dates

Study Major Dates

• Study Start (Actual): December 30, 2024
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): June 1, 2028

Study Registration Dates

• First Submitted: February 8, 2024
• First Submitted That Met QC Criteria: February 8, 2024
• First Posted (Actual): February 20, 2024

Study Record Updates

• Last Update Posted (Actual): July 3, 2025
• Last Update Submitted That Met QC Criteria: July 1, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: Stress Disorders, Post-Traumatic; Mental Disorders; Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; PTSD, Post-Traumatic Stress Disorder; VNS, Vagus Nerve Stimulation; TPT, Targeted Plasticity Therapy; ReStore System; PE, Prolonged Exposure Therapy
• Additional Relevant MeSH Terms: Trauma and Stressor Related Disorders; Mental Disorders; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic
• Other Study ID Numbers: IRB-24-22; HT94252310818 (Other Grant/Funding Number: CDMRP); 175181 (Other Identifier: The University of Texas Health Science Center at San Antonio)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No