NCT04064762

Brief Summary

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.

Trial Health

55
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
9

participants targeted

Target at below P25 for not_applicable

Timeline
Completed

Started Dec 2020

Longer than P75 for not_applicable

Geographic Reach
1 country

1 active site

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

July 31, 2019

Completed
22 days until next milestone

First Posted

Study publicly available on registry

August 22, 2019

Completed
1.3 years until next milestone

Study Start

First participant enrolled

December 16, 2020

Completed
2.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2023

Completed
1.2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2024

Completed
Last Updated

January 5, 2023

Status Verified

January 1, 2023

Enrollment Period

2.1 years

First QC Date

July 31, 2019

Last Update Submit

January 4, 2023

Conditions

Post Traumatic Stress Disorder

Keywords

Vagus Nerve Stimulation (VNS)Prolonged Exposure Therapy (PE)PTSDPost Traumatic Stress Disorder

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (5)

  • Clinician-Administered PTSD Scale for DSM-5 (CAPS-5)

    Weeks 1, 9, 15, 19, 36, 62

  • PTSD Checklist for DSM-5 (PCL-5)

    Weeks 1, 9-15, 19, 36, 62

  • Patient Health Questionnaire-9 (PHQ-9)

    Weeks 1, 9-15, 19, 36, 62

  • Generalized Anxiety Disorder 7-item Scale (GAD-7)

    Weeks 9, 15, 19, 36, 62

  • Posttraumatic Cognitions Inventory (PTCI)

    Weeks 9-15, 19, 36, 62

Study Arms (1)

Vagus Nerve Stimulation + Prolonged Exposure Therapy

EXPERIMENTAL

Study treatment is vagus nerve stimulation (VNS) delivered during Prolonged Exposure Therapy.

Device: Paired Vagus Nerve Stimulation

Interventions

Paired Vagus Nerve StimulationDEVICE

Stimulation of the vagus nerve that is paired with Prolonged Exposure Therapy.

Also known as: VNS, vagus nerve stimulation, paired VNS
Vagus Nerve Stimulation + Prolonged Exposure Therapy

Eligibility Criteria

Age18 Years - 64 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • 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

You may not qualify if:

  • 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.
  • +5 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Baylor University Medical Center

Dallas, Texas, 75246, United States

Location

Related Publications (15)

  • American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th ed. Washington, DC: American Psychiatric Association; 2013.

    BACKGROUND

  • 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.

    PMID: 15609737BACKGROUND

  • 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.

    PMID: 21228773BACKGROUND

  • 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.

    BACKGROUND

  • 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.

    PMID: 26691504BACKGROUND

  • 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.

    PMID: 26691507BACKGROUND

  • 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.

    PMID: 20855048BACKGROUND

  • 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.

    PMID: 22238857BACKGROUND

  • 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.

    PMID: 24309259BACKGROUND

  • 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.

    BACKGROUND

  • 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.

    PMID: 11556941BACKGROUND

  • 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.

    PMID: 20546985BACKGROUND

  • 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.

    PMID: 9881538BACKGROUND

  • 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.

    PMID: 16717171BACKGROUND

  • Powers MB, Hays SA, Rosenfield D, Porter AL, Gallaway H, Chauvette G, Smits JAJ, Warren AM, Douglas M, Naftalis R, Wigginton JG, Foreman M, Kilgard MP, Rennaker RL. Vagus nerve stimulation therapy for treatment-resistant PTSD. Brain Stimul. 2025 May-Jun;18(3):665-675. doi: 10.1016/j.brs.2025.03.007. Epub 2025 Mar 15.

    PMID: 40097094DERIVED

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic

Interventions

Vagus Nerve Stimulation

Condition Hierarchy (Ancestors)

Stress Disorders, TraumaticTrauma and Stressor Related DisordersMental Disorders

Intervention Hierarchy (Ancestors)

Electric Stimulation TherapyTherapeutics

Study Officials

  • Michael Kilgard, PhD

    The University of Texas at Dallas

    PRINCIPAL INVESTIGATOR

  • Robert Rennaker, PhD

    The University of Texas at Dallas

    PRINCIPAL INVESTIGATOR

  • Seth Hays, PhD

    The University of Texas at Dallas

    STUDY DIRECTOR

  • Jane Wigginton, MD

    University of Texas Southwestern Medical Center

    PRINCIPAL INVESTIGATOR

  • Michael Foreman, MD FACS

    Baylor Health Care System

    PRINCIPAL INVESTIGATOR

  • 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

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 31, 2019

First Posted

August 22, 2019

Study Start

December 16, 2020

Primary Completion

February 1, 2023

Study Completion

April 1, 2024

Last Updated

January 5, 2023

Record last verified: 2023-01

Data Sharing

IPD Sharing
Will not share

Locations

US(1)