Post-traumatic Stress DisorderSO-PTSDNCT01627301
Sympathetic Overactivity in Post-traumatic Stress Disorder
A study testing Device-Guided Breathing (DGB) and Transcutaneous Vagal Nerve Stimulation (tVNS) in people with Post-traumatic Stress Disorder and Prehypertension, run by Emory University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Post-traumatic Stress Disorder, Prehypertension
- What is being tested?
- Device-Guided Breathing (DGB) and Transcutaneous Vagal Nerve Stimulation (tVNS)
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 120 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2012to Dec 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- prehypertensive and normotensive veterans with PTSD, and prehypertensive and normotensive veterans without PTSD (controls)
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Jeanie Park, MD contact
United States1 site, 1 recruiting
- Recruiting
Atlanta VA Medical Center
Decatur, Georgia, 30033
About this study
Official title: Mechanisms of Sympathetic Overactivity in Post-traumatic Stress Disorder
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.
Read the detailed description
PTSD is highly prevalent in both the military and general population. Because of the tremendous deleterious mental health and socioeconomic impact of PTSD, research to understand and treat all aspects of PTSD is vitally important. One less recognized but highly significant consequence of PTSD is an increased risk of hypertension, cardiovascular disease (CV) disease, and its risk factors. Despite the epidemiologic data demonstrating increased CV risk in PTSD, very little is known about underlying mechanisms. This project will help fill this gap by examining the mechanistic role of sympathetic overactivation in PTSD. Sympathetic hyperactivity has a major role in causing and sustaining hypertension, and contributes to the development of heart failure, arrhythmias, and atherogenesis. Moreover, exaggerated SNS responses during mental stress are associated with an increased risk of hypertension and CV disease.
Slow breathing is an integral part of many ancient meditative practices that are purported to have beneficial physiologic and psychological effects. Clinical applicability of slow breathing requires a method for delivering slow breathing exercises to outpatients on a consistent basis. This can be achieved through device-guided slow breathing (DGB) in which breathing rate is slowed to < 10 breaths/min via an interactive biofeedback device. The RESPeRATE (Intercure, Inc.) device is currently FDA approved for adjunctive treatment of high blood pressure and reduction of stress. This device includes a belt-type respiratory sensor, earbuds to provide audio feedback, and microprocessor that measures adherence and success at achieving slow breathing rates.
Vagal nerve stimulation has been shown in both animal and human studies to safely and effectively reduce sympathetic activity and inflammation. 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. Prior studies have shown that transcutaneous vagal nerve stimulation safely and effectively reduced muscle sympathetic nerve activity in healthy humans and improved heart rate variability, indicating a decrease in sympathetic nervous system (SNS) activity, and a shift in cardiac autonomic function toward parasympathetic (PNS) predominance.
The purpose of this study is to determine if device-guided slow breathing or tVNS improves sympathetic activity and vascular function in persons with PTSD. Participants will be randomized to 15 minutes daily of DGB vs sham-DGB, or tVNS vs. sham-tVNS for 8 weeks.
- Conditions
- Post-traumatic Stress Disorder, Prehypertension
- Being tested
- Device-Guided Breathing (DGB), Sham DGB, Transcutaneous Vagal Nerve Stimulation (tVNS), Sham tVNS
- Medical subject headings
- Stress Disorders, Post-Traumatic, Prehypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Device-Guided Breathing (DGB)Device
Also called RESPeRATE
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.
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.
Transcutaneous Vagal Nerve Stimulation (tVNS)Device
Also called gammaCore
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.
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.
| Study group | Role | What they receive |
|---|---|---|
| Device-guided Breathing (DGB) | Experimental | Participants randomized to the DGB group use a device to guide their breathing to a slow breathing rate. Receives: 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. Receives: 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. Receives: 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. Receives: Device: Sham tVNS |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline, Week 8
Secondary outcomes (2)
Endothelial Function
Endothelial Function will be measured using peripheral arterial tonometry.
Measured: Baseline, Week 8
Vascular Stiffness
Vascular stiffness will be measured noninvasively using pulse wave analysis and pulse wave velocity.
Measured: Baseline, Week 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jun 2012 (estimated)
- Study startJul 2012
- Primary completionDec 2027 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Post-traumatic Stress DisorderStudies of the same condition, open and under way.
- More trials run by Emory UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Collaborators
- US Department of Veterans Affairs
- Responsible party
- Principal investigator, Jeanie Park, Emory University
- Investigators
- Jeanie Park, MD, Principal investigator, Emory University and the Atlanta VA Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01627301
- Sponsor's protocol ID
- IRB00054697
- Other IDs
- 2025P011325
- Acronym
- SO-PTSD
- Status last verified
- Jan 2026
- First submitted
- 21 Jun 2012
- Last updated
- 15 Jan 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
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.
PubMed 32847397
Study at a glance
From the registry record, last updated by the sponsor on 15 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mechanisms of Sympathetic Overactivity in Post-traumatic Stress Disorder
- ClinicalTrials.gov ID
- NCT01627301
- Acronym / sponsor ID
- SO-PTSD / IRB00054697
- Conditions
- Post-traumatic Stress Disorder, Prehypertension
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Collaborators
- US Department of Veterans Affairs
- Study start
- Jul 2012 (actual)
- Primary completion
- Dec 2027 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 25 Jun 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
PTSD is highly prevalent in both the military and general population. Because of the tremendous deleterious mental health and socioeconomic impact of PTSD, research to understand and treat all aspects of PTSD is vitally important. One less recognized but highly significant consequence of PTSD is an increased risk of hypertension, cardiovascular disease (CV) disease, and its risk factors. Despite the epidemiologic data demonstrating increased CV risk in PTSD, very little is known about underlying mechanisms. This project will help fill this gap by examining the mechanistic role of sympathetic overactivation in PTSD. Sympathetic hyperactivity has a major role in causing and sustaining hypertension, and contributes to the development of heart failure, arrhythmias, and atherogenesis. Moreover, exaggerated SNS responses during mental stress are associated with an increased risk of hypertension and CV disease.
Slow breathing is an integral part of many ancient meditative practices that are purported to have beneficial physiologic and psychological effects. Clinical applicability of slow breathing requires a method for delivering slow breathing exercises to outpatients on a consistent basis. This can be achieved through device-guided slow breathing (DGB) in which breathing rate is slowed to < 10 breaths/min via an interactive biofeedback device. The RESPeRATE (Intercure, Inc.) device is currently FDA approved for adjunctive treatment of high blood pressure and reduction of stress. This device includes a belt-type respiratory sensor, earbuds to provide audio feedback, and microprocessor that measures adherence and success at achieving slow breathing rates.
Vagal nerve stimulation has been shown in both animal and human studies to safely and effectively reduce sympathetic activity and inflammation. 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. Prior studies have shown that transcutaneous vagal nerve stimulation safely and effectively reduced muscle sympathetic nerve activity in healthy humans and improved heart rate variability, indicating a decrease in sympathetic nervous system (SNS) activity, and a shift in cardiac autonomic function toward parasympathetic (PNS) predominance.
The purpose of this study is to determine if device-guided slow breathing or tVNS improves sympathetic activity and vascular function in persons with PTSD. Participants will be randomized to 15 minutes daily of DGB vs sham-DGB, or tVNS vs. sham-tVNS for 8 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Device-guided Breathing (DGB) | Experimental | Device: Device-Guided Breathing (DGB)Participants randomized to the DGB group use a device to guide their breathing to a slow breathing rate. |
| Sham DGB | Sham comparator | Device: Sham DGBParticipants 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. |
| Transcutaneous Vagal Nerve Stimulation (tVNS) | Experimental | Device: Transcutaneous Vagal Nerve Stimulation (tVNS)Participants randomized to use a tVNS device to deliver mild electrical stimulation to the vagal nerve. |
| Sham tVNS | Sham comparator | Device: Sham tVNSParticipants randomized to use the sham tVNS device which vibrates but does not stimulate the vagal nerve. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- prehypertensive and normotensive veterans with PTSD, and prehypertensive and normotensive veterans without PTSD (controls)
Key exclusion criteria (8 listed)
- heart or vascular disease
- illicit drug use within the last 6 months
- excessive alcohol use (>2 drinks per day)
- pregnancy
- autonomic dysfunction
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Device-Guided Breathing (DGB)Also: RESPeRATEThe 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. | Device | Device-guided Breathing (DGB) |
| Sham DGBThe 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. | Device | Sham DGB |
| Transcutaneous Vagal Nerve Stimulation (tVNS)Also: gammaCoretVNS 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. | Device | Transcutaneous Vagal Nerve Stimulation (tVNS) |
| Sham tVNSSham 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. | Device | Sham tVNS |
Primary outcome
Change in Muscle Sympathetic Nerve Activity (MSNA) Burst Frequency at Rest
Time frame: Baseline, Week 8
MSNA is assessed with microneurography where a tungsten microelectrode inserted in the nerve records sympathetic nerve activity.
Change in Baroreflex Sensitivity (BRS) at Rest
Time frame: Baseline, Week 8
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.
Change in MSNA Burst Frequency While Under Mental Stress
Time frame: Baseline, Week 8
Mental stress will be induced by having participants complete mental arithmetic and with a combat virtual reality clip.
Change in BRS While Under Mental Stress
Time frame: Baseline, Week 8
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.
2 secondary outcomes
Endothelial Function
Time frame: Baseline, Week 8
Vascular Stiffness
Time frame: Baseline, Week 8
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jan 2026.
- Results publication: PubMed 32847397Fonkoue 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Jeanie Park, MD contact
Jeanie Park, MD principal investigator
Emory University and the Atlanta VA Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Device-Guided Breathing (DGB) and Transcutaneous Vagal Nerve Stimulation (tVNS) in people with Post-traumatic Stress Disorder and Prehypertension, run by Emory University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 15 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Deirdre Dixon, MS (404-321-6111 ext. 207040, deirdre.dixon@emory.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Muscle Sympathetic Nerve Activity (MSNA) Burst Frequency at Rest (time frame: Baseline, Week 8). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01627301, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jan 2026.