Vagal Nerve Stimulation to Probe Inflammation and Brain in Post-traumatic Stress

NCT03858985 | Completed Phase 1 DMC FDA Device

• 1 other identifier: D2920-W
• Study Type: interventional
• Target: 88
• Locations: 1 country
• Sites: 1

Brief Summary

The proposal aims to determine if non-invasive vagus nerve stimulation(nVNS) will alter: 1) the peripheral inflammatory biomarker profile, 2) the neural correlates of change in pain stimuli and 3) PTSD symptom severity and 4) life quality and function in Veterans with PTSD. The planned inflammatory biomarker and neuroimaging results can 1) promote knowledge of inflammatory and neurobiological mechanisms that contribute to pain in PTSD, and 2) advance the ability to provide targeted neuromodulation based interventions that support improved life quality and function for Veterans. These goals are consistent with the VA's mission to sponsor research examining variables related to pathogenesis, diagnosis, and(ultimately) treatment of neuropsychiatric disorders.

Conditions

Post-traumatic Stress

Outcome Measures

Primary Outcomes (2)

• Neural Effects Measured by Functional MRI

  Examining fMRI derived hemodynamic response curve during rest and pain challenge carried out at baseline to week 1 of 1x daily treatment.

  Functional Imaging Brain Response Measured with Functional MRI: [Time Frame: baseline to week 1 of 1x daily treatment)]

• Peripheral Blood Inflammatory Cytokine Measurement

  Peripheral Blood will be drawn to examine concentrations of plasma cytokines in response to sham or nVNS. Cytokine concentrations are measured with in tube whole blood culture system. Peripheral blood cytokine concentration will be quantified in picogram/milliliter.

  Peripheral Blood Inflammatory Cytokine Measurement: [Time Frame: baseline to week 1 of 1x daily treatment)]

Secondary Outcomes (3)

• Clinician Administered PTSD Scale

  Clinician Administered PTSD Scale: [Time Frame: baseline to week 1 of 1x daily treatment)]

• Sheehan Disability Scale (SDS)

  Sheehan Disability Scale (SDS): [Time Frame: baseline to week 1 of 1x daily treatment and post treatment week 5)]

• WHODAS 2.0

  WHODAS 2.0: [Time Frame: baseline to week 1 of 1x daily treatment and post treatment week 5)]

Study Arms (2)

Transcutaneous Vagus Nerve Stimulation

ACTIVE COMPARATOR

Cervical Transcutaneous vagus nerve stimulation. Participants will undergo once daily cervical transcutaneous vagus nerve stimulation.

Device: Cervical Transcutaneous Vagus Nerve Stimulation (Active Comparator)

Sham Vagus Nerve Stimulation

SHAM COMPARATOR

Sham Cervical Transcutaneous Vagus Nerve Stimulation. Participants will undergo once daily sham cervical transcutaneous vagus nerve stimulation.

Device: Cervical Transcutaneous Vagus Nerve Stimulation (Sham Comparator)

Interventions

Cervical Transcutaneous Vagus Nerve Stimulation (Active Comparator) DEVICE

Both sham and active nVNS treatment produce low-voltage electrical signal that induce reliable sensation on subject skin on upper anterior cervical area (overlying carotid artery).

Transcutaneous Vagus Nerve Stimulation

Cervical Transcutaneous Vagus Nerve Stimulation (Sham Comparator) DEVICE

Both sham and active nVNS treatment produce low-voltage electrical signal that induce reliable sensation on subject skin on upper anterior cervical area (overlying carotid artery).

Sham Vagus Nerve Stimulation

Eligibility Criteria

• Age: 21 Years - 65 Years
• Gender Eligibility Details: No women will be enrolled in this study. Prior research suggests that inflammation is sex dependent in individuals with PTSD while inflammation-induced alteration of brain response is also sex specific. There is a known sex difference in the prevalence of PTSD, suggesting that gender may play a role in the pathophysiology of PTSD. Gender differences have repeatedly been shown in human experimental pain paradigms. Taken together only male subjects will be enrolled to decrease variability in measures of pain and peripheral inflammation that could also have sex specific correlation fMRI brain response. If significant effects are demonstrated with this study follow up grant proposals will include female subjects
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male subjects between 21 and 65 years, any race or ethnicity.
• For PTSD: Previously deployed, experienced a traumatic event, and meets Clinician-Administered PTSD Scale for DSM-5(CAPS-5) symptom cluster severity criteria for PTSD diagnosis, as well as CAPS total cut-off score \> 33. 3. For CC: Previously deployed, experienced a traumatic event, and fails to meet CAPS-5 symptom cluster severity criteria for PTSD diagnosis with CAPS total cut-off score \< 20.
• Capable of complying with study schedule, procedures, and speaks English.
• Able to provide voluntary written informed consent prior to initiation of Visit 1; and be able to commit to the return visit at the end of the study.

You may not qualify if:

• Rule out significant mental illness, e.g. psychosis, bipolar disorder as well as major depression pre-dating PTSD, based on Structured Clinical Interview for DSM-5(SCID) interview.
• At risk for suicide or homicide(based upon Columbia Suicide Risk Severity Scale(C-SSRS) or BDI-2 screen and follow-up clinical interview).
• Any subject who has undergone evidence-based treatment(CPT or PE) within one month prior to study enrollment or plans to undergo CPT or PE during the study.
• History of head trauma involving loss of consciousness\>1 minute and post-concussive symptoms(PCS).
• Chronic pain as defined by pain persisting beyond its ecological alerting function, and clinically defined as lasting longer than 3 months, and/or currently under the care of a chronic pain physician.
• Any condition or therapy that, in the opinion of the investigator and research team, may be significantly worsened by the administration of study treatment or is likely to interfere with the successful collection of the measures required.
• Clinically significant uncontrolled/unstable medical illness or clinically significant surgery within 1 month of the screening visit.
• Evidence of a maladaptive pattern of alcohol use or abuse(based on AUDIT-C interview) one month prior to the screening visit and or illicit drug use or abuse as measured by urine screen positive for illicit substances at the screening Visit 1 or follow up Visit 2.
• Participation in a pharmaceutical trial or exposure to investigational drugs within 1 month of the screening visit.
• Standard of care medications used to treat PTSD will be continued. Any subject that takes anti-inflammatory medications for chronic medical conditions or takes other medications for chronic pain will be excluded.
• Vagus nerve stimulation related criteria: history of carotid endarterectomy, severe carotid artery disease\[e.g. bruits on physical exam or history of transient ischemic attack(TIA) or stroke\], congestive heart failure(CHF), cardiac arrhythmia, known severe coronary artery disease or recent myocardial infarction(within 5 years), or a history or seizure or syncope(within the last 1 year), or prior neck surgery will be excluded.

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (1)

VA San Diego Healthcare System, San Diego, CA

San Diego, California, 92161-0002, United States

Location

Study Officials

• Imanuel R Lerman, MD MSc

  VA San Diego Healthcare System, San Diego, CA

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The study staff and principle investigator will be blinded to treatment and therefore this study is considered randomized and double blinded.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: A sham and active non-invasive vagus nerve stimulator (nVNS) will be used. Both sham and active produce reliable sensation on subject skin over the cervical neck area. The sham device is identical in appearance to the nVNS device. Both devices carry out stimulation for the exact same time period, approximately 2 minutes. Subjects are assigned to sham and nVNS device therapy given once daily for 1 week.

Study Record Dates

• First Submitted: February 13, 2019
• First Posted: March 1, 2019
• Study Start: February 4, 2019
• Primary Completion: March 31, 2025
• Study Completion: March 31, 2025
• Last Updated: April 10, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)