Clinical trial NCT04064762: Targeted Plasticity Therapy for Posttraumatic Stress Disorder
Official title: Targeted Plasticity Therapy for Posttraumatic Stress Disorder
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Post Traumatic Stress Disorder
Keywords: Vagus Nerve Stimulation (VNS)
Prolonged Exposure Therapy (PE)
PTSD
Post Traumatic Stress Disorder
Lead sponsor: Baylor Research Institute
Sponsor class: OTHER
Collaborators: name: Defense Advanced Research Projects Agency
name: The University of Texas at Dallas
name: University of Texas Southwestern Medical Center
First posted: 2019-08-22
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Incidence of Adverse Events [Device Safety]
timeFrame: From Week 1 through study follow-up, approximately two years from the date of implant
Secondary outcomes:
measure: Clinician-Administered PTSD Scale for DSM-5 (CAPS-5)
timeFrame: Weeks 1, 9, 15, 19, 36, 62
measure: PTSD Checklist for DSM-5 (PCL-5)
timeFrame: Weeks 1, 9-15, 19, 36, 62
measure: Patient Health Questionnaire-9 (PHQ-9)
timeFrame: Weeks 1, 9-15, 19, 36, 62
measure: Generalized Anxiety Disorder 7-item Scale (GAD-7)
timeFrame: Weeks 9, 15, 19, 36, 62
measure: Posttraumatic Cognitions Inventory (PTCI)
timeFrame: Weeks 9-15, 19, 36, 62
Other outcomes:
Locations:
city: Dallas
country: United States
facility: Baylor University Medical Center
state: Texas
Study officials:
affiliation: University of Texas at Dallas
name: Michael Kilgard, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Texas at Dallas
name: Robert Rennaker, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Texas at Dallas
name: Seth Hays, PhD
role: STUDY_DIRECTOR
affiliation: University of Texas Southwestern Medical Center
name: Jane Wigginton, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Baylor Health Care System
name: Michael Foreman, MD FACS
role: PRINCIPAL_INVESTIGATOR
affiliation: Baylor Health Care System
name: Mark Powers, PhD
role: STUDY_DIRECTOR
affiliation: Baylor Health Care System
name: Richard Naftalis, MD, FAANS, FACS
role: STUDY_DIRECTOR
affiliation: Baylor Health Care System
name: Ann Marie Warren, PhD
role: STUDY_DIRECTOR
affiliation: The University of Texas at Austin
name: Jasper Smits, PhD
role: STUDY_DIRECTOR
References:
citation: American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th ed. Washington, DC: American Psychiatric Association; 2013.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.