NCT01627301

Brief Summary

Post-traumatic stress disorder (PTSD) is a highly prevalent anxiety disorder that is associated with an increased risk of cardiovascular (CV) disease and hypertension. One potential mechanism is overactivation of the sympathetic nervous system (SNS), both at rest and particularly during stress. This study will evaluate whether 8 weeks of daily DGB therapy or transcutaneous vagus nerve stimulation (tVNS) therapy improves SNS activity at rest and during stress.

Trial Health

77
On Track

Trial Health Score

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

Enrollment
120

participants targeted

Target at P50-P75 for not_applicable

Timeline
18mo left

Started Jul 2012

Longer than P75 for not_applicable

Geographic Reach
1 country

1 active site

Status
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

Study Progress91%
Jul 2012Dec 2027

First Submitted

Initial submission to the registry

June 21, 2012

Completed
4 days until next milestone

First Posted

Study publicly available on registry

June 25, 2012

Completed
6 days until next milestone

Study Start

First participant enrolled

July 1, 2012

Completed
15.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2027

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2027

Last Updated

January 15, 2026

Status Verified

January 1, 2026

Enrollment Period

15.4 years

First QC Date

June 21, 2012

Last Update Submit

January 13, 2026

Conditions

Post-traumatic Stress DisorderPrehypertension

Outcome Measures

Primary Outcomes (4)

  • Change in Muscle Sympathetic Nerve Activity (MSNA) Burst Frequency at Rest

    MSNA is assessed with microneurography where a tungsten microelectrode inserted in the nerve records sympathetic nerve activity.

    Baseline, Week 8

  • Change in Baroreflex Sensitivity (BRS) at Rest

    Arterial baroreflex sensitivity (BRS) will be tested using pharmacologic manipulation of blood pressure at rest. BRS is assessed by measuring changes in MSNA and heart rate during arterial blood pressure changes induced by nitroprusside and phenylephrine.

    Baseline, Week 8

  • Change in MSNA Burst Frequency While Under Mental Stress

    Mental stress will be induced by having participants complete mental arithmetic and with a combat virtual reality clip.

    Baseline, Week 8

  • Change in BRS While Under Mental Stress

    Mental stress will be induced by having participants complete mental arithmetic and with a combat virtual reality clip. Arterial baroreflex sensitivity (BRS) will be tested using pharmacologic manipulation of blood pressure at rest and during mental stress.

    Baseline, Week 8

Secondary Outcomes (2)

  • Endothelial Function

    Baseline, Week 8

  • Vascular Stiffness

    Baseline, Week 8

Study Arms (4)

Device-guided Breathing (DGB)

EXPERIMENTAL

Participants randomized to the DGB group use a device to guide their breathing to a slow breathing rate.

Device: Device-Guided Breathing (DGB)

Sham DGB

SHAM COMPARATOR

Participants randomized to the sham DGB group use a device identical to the DGB device but respiratory rates are not guided lower than the physiological rate.

Device: Sham DGB

Transcutaneous Vagal Nerve Stimulation (tVNS)

EXPERIMENTAL

Participants randomized to use a tVNS device to deliver mild electrical stimulation to the vagal nerve.

Device: Transcutaneous Vagal Nerve Stimulation (tVNS)

Sham tVNS

SHAM COMPARATOR

Participants randomized to use the sham tVNS device which vibrates but does not stimulate the vagal nerve.

Device: Sham tVNS

Interventions

Device-Guided Breathing (DGB)DEVICE

The RESPeRATE device will be used for 15 minutes of device-guided breathing daily for 8 weeks. The participant places the elastic belt with a respiration sensor around the upper abdomen, and wears earbuds for audio feedback. The device monitors the breathing rate, calculates inspiration and expiration times, and generates a personalized melody of two distinct ascending and descending tones for inhalation versus exhalation. Users effortlessly entrain their breathing pattern with the tones, and the device gradually guides the user to a prolonged expiration time and slower respiratory rate (to \< 10 breaths/minute). The device automatically stores usage data, allowing for quantification of adherence and performance.

Also known as: RESPeRATE
Device-guided Breathing (DGB)
Sham DGBDEVICE

The sham device is identical to the DGB device, except it does not guide respiratory rates to slow down and instead maintains a rate of 14 breaths per minute. The sham device is used for 15 minutes per day for 8 weeks.

Sham DGB
Transcutaneous Vagal Nerve Stimulation (tVNS)DEVICE

tVNS is a noninvasive method that involves placing a device over the skin overlying the vagus nerve on the neck. The device delivers mild electrical stimulation, using transcutaneous electrical nerve stimulation (TENS) unit. The stimulation is increased until there is a vibration and slight muscle contraction in the lower face or neck. Then the stimulation is delivered for 2 minutes on the left side of the neck, and on the right side of the neck, for a total of 4 minutes. The tVNS device is used twice daily for 8 weeks.

Also known as: gammaCore
Transcutaneous Vagal Nerve Stimulation (tVNS)
Sham tVNSDEVICE

Sham stimulation is delivered using a device that is identical to the gammaCore device but is programed to deliver a lower frequency that can be felt by the participant but does not actually stimulate the vagus nerve. The sham device is used twice daily for 8 weeks.

Sham tVNS

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • prehypertensive and normotensive veterans with PTSD, and prehypertensive and normotensive veterans without PTSD (controls)

You may not qualify if:

  • heart or vascular disease
  • illicit drug use within the last 6 months
  • excessive alcohol use (\>2 drinks per day)
  • pregnancy
  • autonomic dysfunction
  • medications known to affect SNS (clonidine)
  • treatment with monoamine oxidase (MAO) inhibitors within the last 14 days
  • any serious systemic disease

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Atlanta VA Medical Center

Decatur, Georgia, 30033, United States

RECRUITING

Related Publications (1)

  • Fonkoue IT, Hu Y, Jones T, Vemulapalli M, Sprick JD, Rothbaum B, Park J. Eight weeks of device-guided slow breathing decreases sympathetic nervous reactivity to stress in posttraumatic stress disorder. Am J Physiol Regul Integr Comp Physiol. 2020 Oct 1;319(4):R466-R475. doi: 10.1152/ajpregu.00079.2020. Epub 2020 Aug 26.

    PMID: 32847397RESULT

MeSH Terms

Conditions

Stress Disorders, Post-TraumaticPrehypertension

Condition Hierarchy (Ancestors)

Stress Disorders, TraumaticTrauma and Stressor Related DisordersMental DisordersVascular DiseasesCardiovascular Diseases

Study Officials

  • Jeanie Park, MD

    Emory University and the Atlanta VA Medical Center

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Deirdre Dixon, MS

CONTACT

404-321-6111deirdre.dixon@emory.edu

Jeanie Park, MD

CONTACT

404-321-6111

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor

Study Record Dates

First Submitted

June 21, 2012

First Posted

June 25, 2012

Study Start

July 1, 2012

Primary Completion (Estimated)

December 1, 2027

Study Completion (Estimated)

December 1, 2027

Last Updated

January 15, 2026

Record last verified: 2026-01

Data Sharing

IPD Sharing
Will not share

Locations

US(1)