Targeted Plasticity Therapy for Posttraumatic Stress Disorder

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Post Traumatic Stress Disorder
• Intervention / Treatment: Device: Paired Vagus Nerve Stimulation

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75246
      • Baylor University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Baylor Research Institute
• Collaborators: University of Texas Southwestern Medical Center; The University of Texas at Dallas; Defense Advanced Research Projects Agency
• Investigators: Principal Investigator: Michael Kilgard, PhD, University of Texas at Dallas; Principal Investigator: Robert Rennaker, PhD, University of Texas at Dallas; Study Director: Seth Hays, PhD, University of Texas at Dallas; Principal Investigator: Jane Wigginton, MD, University of Texas Southwestern Medical Center; Principal Investigator: Michael Foreman, MD FACS, Baylor Health Care System; Study Director: Mark Powers, PhD, Baylor Health Care System; Study Director: Richard Naftalis, MD, FAANS, FACS, Baylor Health Care System; Study Director: Ann Marie Warren, PhD, Baylor Health Care System; Study Director: Jasper Smits, PhD, The University of Texas at Austin

Publications and helpful links

General Publications

• Kroenke K, Spitzer RL, Williams JB. The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med. 2001 Sep;16(9):606-13. doi: 10.1046/j.1525-1497.2001.016009606.x.
• Spitzer RL, Kroenke K, Williams JB, Lowe B. A brief measure for assessing generalized anxiety disorder: the GAD-7. Arch Intern Med. 2006 May 22;166(10):1092-7. doi: 10.1001/archinte.166.10.1092.
• Sheehan DV, Lecrubier Y, Sheehan KH, Amorim P, Janavs J, Weiller E, Hergueta T, Baker R, Dunbar GC. The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry. 1998;59 Suppl 20:22-33;quiz 34-57.
• Engineer ND, Riley JR, Seale JD, Vrana WA, Shetake JA, Sudanagunta SP, Borland MS, Kilgard MP. Reversing pathological neural activity using targeted plasticity. Nature. 2011 Feb 3;470(7332):101-4. doi: 10.1038/nature09656. Epub 2011 Jan 12.
• Powers MB, Halpern JM, Ferenschak MP, Gillihan SJ, Foa EB. A meta-analytic review of prolonged exposure for posttraumatic stress disorder. Clin Psychol Rev. 2010 Aug;30(6):635-41. doi: 10.1016/j.cpr.2010.04.007. Epub 2010 May 2.
• American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th ed. Washington, DC: American Psychiatric Association; 2013.
• Corson K, Gerrity MS, Dobscha SK. Screening for depression and suicidality in a VA primary care setting: 2 items are better than 1 item. Am J Manag Care. 2004 Nov;10(11 Pt 2):839-45.
• Foa EB, Ehlers A, Clark DM, Tolin DF, Orsillo SM. The Posttraumatic Cognitions Inventory (PTCI): Development and validation. Psychol Assess 11(3): 303-314, 1999.
• Foa EB, McLean CP, Zang Y, Zhong J, Powers MB, Kauffman BY, Rauch S, Porter K, Knowles K. Psychometric properties of the Posttraumatic Diagnostic Scale for DSM-5 (PDS-5). Psychol Assess. 2016 Oct;28(10):1166-1171. doi: 10.1037/pas0000258. Epub 2015 Dec 21.
• Foa EB, McLean CP, Zang Y, Zhong J, Rauch S, Porter K, Knowles K, Powers MB, Kauffman BY. Psychometric properties of the Posttraumatic Stress Disorder Symptom Scale Interview for DSM-5 (PSSI-5). Psychol Assess. 2016 Oct;28(10):1159-1165. doi: 10.1037/pas0000259. Epub 2015 Dec 21.
• Gilboa-Schechtman E, Foa EB, Shafran N, Aderka IM, Powers MB, Rachamim L, Rosenbach L, Yadin E, Apter A. Prolonged exposure versus dynamic therapy for adolescent PTSD: a pilot randomized controlled trial. J Am Acad Child Adolesc Psychiatry. 2010 Oct;49(10):1034-42. doi: 10.1016/j.jaac.2010.07.014. Epub 2010 Sep 6. Erratum In: J Am Acad Child Adolesc Psychiatry. 2016 Oct;55(10):920.
• Goodson J, Helstrom A, Halpern JM, Ferenschak MP, Gillihan SJ, Powers MB. Treatment of posttraumatic stress disorder in U.S. combat veterans: a meta-analytic review. Psychol Rep. 2011 Oct;109(2):573-99. doi: 10.2466/02.09.15.16.PR0.109.5.573-599.
• Hays SA, Rennaker RL, Kilgard MP. Targeting plasticity with vagus nerve stimulation to treat neurological disease. Prog Brain Res. 2013;207:275-99. doi: 10.1016/B978-0-444-63327-9.00010-2.
• Hembree EA, Rauch SAM, Foa EB. Beyond the manual: The insider's guide to Prolonged Exposure therapy for PTSD. Cogn Behav Pract 10(1): 22-30, 2003.

Study record dates

Study Major Dates

• Study Start (Actual): December 16, 2020
• Primary Completion (Anticipated): February 1, 2023
• Study Completion (Anticipated): April 1, 2024

Study Registration Dates

• First Submitted: July 31, 2019
• First Submitted That Met QC Criteria: August 19, 2019
• First Posted (Actual): August 22, 2019

Study Record Updates

• Last Update Posted (Actual): January 5, 2023
• Last Update Submitted That Met QC Criteria: January 4, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: PTSD; Post Traumatic Stress Disorder; Vagus Nerve Stimulation (VNS); Prolonged Exposure Therapy (PE)
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Trauma and Stressor Related Disorders; Disease; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic
• Other Study ID Numbers: 019-280; N66001-15-2-4057 (Other Grant/Funding Number: Defense Advanced Research Projects Agency (DARPA))

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.: Yes