Stress Disorders, Post-TraumaticPhase 2ANG-PNCT02560805
Role of Sympathetic Overactivity and Angiotensin II in PTSD and CV
A Phase 2 study testing Microneurography, Combat virtual reality video clip and Handgrip Exercise in people with Stress Disorders, Post-Traumatic, run by Emory University at 1 site in United States.
Trial summary
The purpose of this study is to find out why patients with post-traumatic stress disorder (PTSD) have an increased risk for heart disease and high blood pressure later in life. A second purpose is to find out what causes PTSD patients to have high adrenaline levels 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
- Stress Disorders, Post-Traumatic
- What is being tested?
- Microneurography, Combat virtual reality video clip and Handgrip Exercise
- Type of treatment
- Pill or oral medicine, Injection or infusion, Medical device, Surgery or procedure, Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 134 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2015to 30 Mar 2027
- Phase
- Phase 2
- 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
- veterans ages 18-65 years old with PTSD and without PTSD (controls) matched for age, gender, and race.
Who cannot join
- pregnancy
- hypertension
- diabetes
- heart or vascular disease
- illicit drug use
- excessive alcohol use (>2 drinks per day)
Show all 17Show fewer
- hyperlipidemia
- autonomic dysfunction
- current treatment with clonidine, beta blockers, angiotensin-converting-enzyme (ACE) inhibitors, or angiotensin II receptor blockers (ARBs)
- treatment with monoamine oxidase (MAO) inhibitors within the last 14 days
- any serious systemic disease
- chronic kidney disease defined as estimated glomerular filtration rate (GFR) < 60 cc/min
- hyperkalemia (serum potassium > 5 meq/dL)
- systolic blood pressure < 100 mm Hg
- diastolic blood pressure < 60 mm Hg
- heart rate < 50 beats/min
- known hypersensitivity to ARBs or beta blockers
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Atlanta VA Medical Center
Decatur, Georgia, 30033
About this study
Official title: Post-Traumatic Stress Disorder and Cardiovascular Disease Risk: Role of Sympathetic Overactivity and Angiotensin II
The purpose of this study is to find out why patients with post-traumatic stress disorder (PTSD) have an increased risk for heart disease and high blood pressure later in life. A second purpose is to find out what causes PTSD patients to have high adrenaline levels during stress. This study will also test if a medicine called losartan improves high adrenaline levels in patients with PTSD and if a certain gene that has to do with high blood pressure might be associated with high adrenaline levels.
Read the detailed description
More than 2,000,000 soldiers have been deployed to Iraq and Afghanistan in the past decade as part of Operation Enduring Freedom/ Operation Iraqi Freedom/ Operation New Dawn (OEF/OIF/OND), and are returning with high rates of post-traumatic stress disorder (PTSD). The prevalence of PTSD in OEF/OIF/OND veterans is estimated at around 11.5-19.9% post deployment, with prevalence rates of 12.1% and 30.9% in older veterans from the Gulf War and Vietnam era, respectively. PTSD is also common in the general population, as 7% of the US population will meet the diagnostic criteria for PTSD in their lifetime. With these extensive and ongoing conflicts, and 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 (CV) disease, and its risk factors. One mechanism likely underlying increased CV risk in PTSD is chronic overactivation of the sympathetic nervous system (SNS). SNS overactivity leads to increased CV risk by increasing blood pressure (BP), and also via BP-independent effects including vascular inflammation, insulin resistance, and myocardial fibrosis.
Chronic inflammation is likely a key culprit contributing to SNS overactivation and blunted baroreflex sensitivity (BRS) in PTSD. In Objective 1 of this study, the researchers will ascertain that humans with PTSD have chronic overactivation of muscle sympathetic nerve activity (MSNA), blunted BRS, and elevated inflammation both at rest and during mental stress.
In addition to chronic inflammation, trauma-related stress is known to activate the renin-angiotensin system (RAS) leading to higher brain angiotensin II (ATII) that is an important mediator of brain inflammation and has a direct sympathoexcitatory effect. Previous studies in both animals and humans with a variety of chronic diseases such as obesity, heart failure, and chronic kidney disease, have shown that blockade of the ATII receptor using angiotensin receptor blockers (ARBs) reduces SNS activity and improves BRS. The extent to which ARB treatment influences SNS activation, BRS, and inflammation in PTSD patients remains unknown. Currently, peripheral sympatholytics such as β-blockers and α-blockers are often prescribed for PTSD symptoms; however, treatment is often complicated by adverse effects including hypotension, orthostasis, fatigue, and erectile dysfunction. In addition, these peripheral sympatholytics cause a reflex increase in central sympathetic output as evidenced by increased MSNA; therefore, these medications may actually contribute to increased CV risk in PTSD. As opposed to peripheral sympatholytics, losartan is well tolerated, without metabolic side effects, and reduces central SNS activation which has potential to impact future CV risk.
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. Another study, found that tVNS acutely improved cardiac baroreflex sensitivity. Since PTSD patients have high SNS, low PNS activity and impaired baroreflex sensitivity, tVNS may be one safe and noninvasive method of improving autonomic function in this patient population. The researchers will test whether tVNS leads to both an acute and sustained improvement in SNS function in PTSD.
Study Objective 2 evaluates the clinical utility of losartan treatment on autonomic control in humans with PTSD. Participants with PTSD will be randomized to treatment with the ARB losartan (25 mg daily) versus the comparison drug atenolol (25 mg daily) for 8-14 weeks. Alternatively, participants with PTSD may be randomized to treatment with tVNS versus sham-tVNS for 8-14 weeks
- Conditions
- Stress Disorders, Post-Traumatic
- Being tested
- Microneurography, Combat virtual reality video clip, Handgrip Exercise, Cold Pressor Test (CPT), Sodium Nitroprusside (SNP)
- Medical subject headings
- Stress Disorders, Post-Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MicroneurographyProcedure or surgery
Skin will be stimulated with a pencil-shaped electrode to find a certain nerve. Once the nerve is found, two tiny sterile wire needles (about the size of acupuncture needles) will be put in the skin. One needle is put just under the skin at a short distance away from the nerve, and the other one into the nerve. The needles are attached to a computer recorder to record the nerve activity. It may take up to one hour to get the needles in the right place. After the tiny needle is in the right place, investigators record nerve activity at rest for about 10 minutes. Then, it will be recorded throughout the rest of the visit (up to 4 hours).
Combat virtual reality video clipBehavioural
Subjects will watch a video clip of combat on a computer screen or wearing video goggles.
Handgrip ExerciseProcedure or surgery
Subjects will squeeze a hand dynamometer intermittently.
Cold Pressor Test (CPT)Procedure or surgery
Subjects' hand will be submerged in cold water (~0-1°C) up to the wrist for 1 minute.
Sodium Nitroprusside (SNP)Drug
Also called Nitropress
Subjects will receive sodium nitroprusside 100 µg, which is bolused through an antecubital intravenous catheter.
PhenylephrineDrug
Subjects will receive phenylephrine 150 µg, which is bolused through an antecubital intravenous catheter 60 seconds after the sodium nitroprusside bolus
LosartanDrug
Also called Cozaar
Losartan will be administered as 25 mg taken orally, once a day for to 8 to 14 weeks.
AtenololDrug
Also called Tenormin
Atenolol will be administered as 25 mg taken orally, once a day for to 8 to 14 weeks.
Transcutaneous Vagal Nerve Stimulation (tVNS)Device
Also called ElectroCore
Transcutaneous vagal nerve stimulation (tVNS) is administered using the gammaCore (ElectroCore) TENS device. The gammaCore device is a multi-use, hand-held, rechargeable portable device consisting of a rechargeable battery, signal generating and amplifying electronics, and two buttons to power on the device and for operator control of the stimulation intensity (range 0-40). A small amount of conductive gel is applied to the pair of stainless steel round discs on the device are placed vertically on the skin with the gel. The stimulation is increased until there is a strong vibration and slight muscle contraction in the lower face or neck (usual intensity 15-25). Then the dose 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 of treatment. Participants will be instructed on the usage of the device and will self-administer up to 4 treatments twice per day.
Sham Transcutaneous Vagal Nerve Stimulation (tVNS)Device
A sham device that is identical to the gammaCore device will be provided to participants. Participants will be instructed on the usage of the device and will self-administer up to 4 treatments twice per day.
| Study group | Role | What they receive |
|---|---|---|
| Veterans with Post-traumatic Stress Disorder (PTSD) | Experimental | For examining Objective 1 of this study, participants with post-traumatic stress disorder (PTSD) will be evaluated using microneurography, static handgrip exercise, cold pressor test, combat virtual reality video clip, and baroreflex sensitivity using sodium nitroprusside and phenylephrine. For the second phase, they will be randomized to either losartan or atenolol. Receives: Procedure: Microneurography; Behavioral: Combat virtual reality video clip; Procedure: Handgrip Exercise; Procedure: Cold Pressor Test (CPT); Drug: Sodium Nitroprusside (SNP); Drug: Phenylephrine |
| Control | Experimental | For examining Objective 1 of this study, healthy controls will be evaluated using microneurography, static handgrip exercise, cold pressor test, combat virtual reality video clip, and baroreflex sensitivity using sodium nitroprusside and phenylephrine. Receives: Procedure: Microneurography; Behavioral: Combat virtual reality video clip; Procedure: Handgrip Exercise; Procedure: Cold Pressor Test (CPT); Drug: Sodium Nitroprusside (SNP); Drug: Phenylephrine |
| Losartan | Experimental | Participants with PTSD randomized to receive losartan for 8 to 14 weeks. Receives: Drug: Losartan |
| Atenolol | Active comparator | Participants with PTSD randomized to receive atenolol for 8 to 14 weeks. Receives: Drug: Atenolol |
| Transcutaneous Vagal Nerve Stimulation (tVNS) | Experimental | Participants with PTSD randomized to receive treatment with tVNS for 8 to 14 weeks. Receives: Device: Transcutaneous Vagal Nerve Stimulation (tVNS) |
| Sham Transcutaneous Vagal Nerve Stimulation (tVNS) | Sham comparator | Participants with PTSD randomized to receive treatment with sham-tVNS for 8 to 14 weeks. Receives: Device: Sham Transcutaneous Vagal Nerve Stimulation (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)
Multiunit postganglionic sympathetic nerve activity is recorded from a tungsten microelectrode inserted into the peroneal nerve with a reference microelectrode inserted in close proximity. Efferent nerve signals are amplified, filtered, rectified and integrated (time constant 0.1 s) to obtain a mean voltage display of MSNA. MSNA bursts are automatically detected using the following criteria: burst-to-noise ratio of 3:1 within a 0.5-s search window, with an average latency of 1.2-1.3 s in burst occurrence from the previous R-wave. MSNA is expressed as burst frequency measured a bursts per minute. MSNA will be examined at rest and during mental stress.
Measured: Baseline, after study intervention (up to 14 weeks)
Secondary outcomes (6)
Change in Baroreflex Sensitivity (BRS)
Afferent sympathetic baroreflex input travels to the brainstem via the glossopharyngeal and vagus nerves and integrate with brainstem centers that regulate efferent SNS (sympathetic BRS) and parasympathetic (cardiovagal BRS) outflow. BRS is defined as the change in interbeat interval (IBI) in milliseconds per unit change in BP. For example, when the BP rises by 10 mmHg and IBI increases by 100 ms, BRS would be 100/10 = 10 ms/mmHg. BRS will be examined at rest and during mental stress.
Measured: Baseline, after study intervention (up to 14 weeks)
C-reactive protein (CRP)
The inflammatory biomarker CRP increases when inflammation is present.
Measured: Baseline, after study intervention (up to 14 weeks)
Interleukin 2 (IL-2)
The inflammatory biomarker IL-2 will be assessed.
Measured: Baseline, after study intervention (up to 14 weeks)
Interleukin 6 (IL-6)
Plasma concentration of the inflammatory biomarker IL-6 will be assessed. IL-6 is increased during injury or illness.
Measured: Baseline, after study intervention (up to 14 weeks)
Angiotensin II (ATII)
ATII will be assessed to determine if ATII signaling contributes to SNS overactivity in PTSD.
Measured: Baseline, after study intervention (up to 14 weeks)
Lipoprotein-associated Phospholipase A2 Mass (Lp-PLA2)
Lp-PLA2 is a unique inflammatory biomarker that is involved in early atherogenesis, endothelial dysfunction, and vascular wall inflammation, which may be elevated in PTSD patients.
Measured: Baseline, after study intervention (up to 14 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Sep 2015 (estimated)
- Study startOct 2015
- Primary completion30 Mar 2027 (estimated)
- Study completion30 Mar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Stress Disorders, Post-TraumaticStudies 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 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 134 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Collaborators
- American Heart Association
- Responsible party
- Principal investigator, Jeanie Park, Emory University
- Investigators
- Jeanie Park, MD, Principal investigator, Emory University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02560805
- Sponsor's protocol ID
- IRB00082400
- Other IDs
- 2025P010213
- Acronym
- ANG-P
- Status last verified
- May 2026
- First submitted
- 24 Sep 2015
- Last updated
- 18 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Post-Traumatic Stress Disorder and Cardiovascular Disease Risk: Role of Sympathetic Overactivity and Angiotensin II
- ClinicalTrials.gov ID
- NCT02560805
- Acronym / sponsor ID
- ANG-P / IRB00082400
- Conditions
- Stress Disorders, Post-Traumatic
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 134 participants (estimated)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Collaborators
- American Heart Association
- Study start
- Oct 2015 (actual)
- Primary completion
- 30 Mar 2027 (estimated)
- Study completion
- 30 Mar 2027 (estimated)
- First posted
- 25 Sep 2015 (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.
The purpose of this study is to find out why patients with post-traumatic stress disorder (PTSD) have an increased risk for heart disease and high blood pressure later in life. A second purpose is to find out what causes PTSD patients to have high adrenaline levels during stress. This study will also test if a medicine called losartan improves high adrenaline levels in patients with PTSD and if a certain gene that has to do with high blood pressure might be associated with high adrenaline levels.
Detailed description
More than 2,000,000 soldiers have been deployed to Iraq and Afghanistan in the past decade as part of Operation Enduring Freedom/ Operation Iraqi Freedom/ Operation New Dawn (OEF/OIF/OND), and are returning with high rates of post-traumatic stress disorder (PTSD). The prevalence of PTSD in OEF/OIF/OND veterans is estimated at around 11.5-19.9% post deployment, with prevalence rates of 12.1% and 30.9% in older veterans from the Gulf War and Vietnam era, respectively. PTSD is also common in the general population, as 7% of the US population will meet the diagnostic criteria for PTSD in their lifetime. With these extensive and ongoing conflicts, and 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 (CV) disease, and its risk factors. One mechanism likely underlying increased CV risk in PTSD is chronic overactivation of the sympathetic nervous system (SNS). SNS overactivity leads to increased CV risk by increasing blood pressure (BP), and also via BP-independent effects including vascular inflammation, insulin resistance, and myocardial fibrosis.
Chronic inflammation is likely a key culprit contributing to SNS overactivation and blunted baroreflex sensitivity (BRS) in PTSD. In Objective 1 of this study, the researchers will ascertain that humans with PTSD have chronic overactivation of muscle sympathetic nerve activity (MSNA), blunted BRS, and elevated inflammation both at rest and during mental stress.
In addition to chronic inflammation, trauma-related stress is known to activate the renin-angiotensin system (RAS) leading to higher brain angiotensin II (ATII) that is an important mediator of brain inflammation and has a direct sympathoexcitatory effect. Previous studies in both animals and humans with a variety of chronic diseases such as obesity, heart failure, and chronic kidney disease, have shown that blockade of the ATII receptor using angiotensin receptor blockers (ARBs) reduces SNS activity and improves BRS. The extent to which ARB treatment influences SNS activation, BRS, and inflammation in PTSD patients remains unknown. Currently, peripheral sympatholytics such as β-blockers and α-blockers are often prescribed for PTSD symptoms; however, treatment is often complicated by adverse effects including hypotension, orthostasis, fatigue, and erectile dysfunction. In addition, these peripheral sympatholytics cause a reflex increase in central sympathetic output as evidenced by increased MSNA; therefore, these medications may actually contribute to increased CV risk in PTSD. As opposed to peripheral sympatholytics, losartan is well tolerated, without metabolic side effects, and reduces central SNS activation which has potential to impact future CV risk.
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. Another study, found that tVNS acutely improved cardiac baroreflex sensitivity. Since PTSD patients have high SNS, low PNS activity and impaired baroreflex sensitivity, tVNS may be one safe and noninvasive method of improving autonomic function in this patient population. The researchers will test whether tVNS leads to both an acute and sustained improvement in SNS function in PTSD.
Study Objective 2 evaluates the clinical utility of losartan treatment on autonomic control in humans with PTSD. Participants with PTSD will be randomized to treatment with the ARB losartan (25 mg daily) versus the comparison drug atenolol (25 mg daily) for 8-14 weeks. Alternatively, participants with PTSD may be randomized to treatment with tVNS versus sham-tVNS for 8-14 weeks
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Veterans with Post-traumatic Stress Disorder (PTSD) | Experimental | Procedure: Microneurography, Behavioral: Combat virtual reality video clip, Procedure: Handgrip Exercise, Procedure: Cold Pressor Test (CPT), Drug: Sodium Nitroprusside (SNP), Drug: PhenylephrineFor examining Objective 1 of this study, participants with post-traumatic stress disorder (PTSD) will be evaluated using microneurography, static handgrip exercise, cold pressor test, combat virtual reality video clip, and baroreflex sensitivity using sodium nitroprusside and phenylephrine. For the second phase, they will be randomized to either losartan or atenolol. |
| Control | Experimental | Procedure: Microneurography, Behavioral: Combat virtual reality video clip, Procedure: Handgrip Exercise, Procedure: Cold Pressor Test (CPT), Drug: Sodium Nitroprusside (SNP), Drug: PhenylephrineFor examining Objective 1 of this study, healthy controls will be evaluated using microneurography, static handgrip exercise, cold pressor test, combat virtual reality video clip, and baroreflex sensitivity using sodium nitroprusside and phenylephrine. |
| Losartan | Experimental | Drug: LosartanParticipants with PTSD randomized to receive losartan for 8 to 14 weeks. |
| Atenolol | Active comparator | Drug: AtenololParticipants with PTSD randomized to receive atenolol for 8 to 14 weeks. |
| Transcutaneous Vagal Nerve Stimulation (tVNS) | Experimental | Device: Transcutaneous Vagal Nerve Stimulation (tVNS)Participants with PTSD randomized to receive treatment with tVNS for 8 to 14 weeks. |
| Sham Transcutaneous Vagal Nerve Stimulation (tVNS) | Sham comparator | Device: Sham Transcutaneous Vagal Nerve Stimulation (tVNS)Participants with PTSD randomized to receive treatment with sham-tVNS for 8 to 14 weeks. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- veterans ages 18-65 years old with PTSD and without PTSD (controls) matched for age, gender, and race.
Key exclusion criteria (17 listed)
- pregnancy
- hypertension
- diabetes
- heart or vascular disease
- illicit drug use
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 |
|---|---|---|
| MicroneurographySkin will be stimulated with a pencil-shaped electrode to find a certain nerve. Once the nerve is found, two tiny sterile wire needles (about the size of acupuncture needles) will be put in the skin. One needle is put just under the skin at a short distance away from the nerve, and the other one into the nerve. The needles are attached to a computer recorder to record the nerve activity. It may take up to one hour to get the needles in the right place. After the tiny needle is in the right place, investigators record nerve activity at rest for about 10 minutes. Then, it will be recorded throughout the rest of the visit (up to 4 hours). | Procedure or surgery | Control, Veterans with Post-traumatic Stress Disorder (PTSD) |
| Combat virtual reality video clipSubjects will watch a video clip of combat on a computer screen or wearing video goggles. | Behavioural | Control, Veterans with Post-traumatic Stress Disorder (PTSD) |
| Handgrip ExerciseSubjects will squeeze a hand dynamometer intermittently. | Procedure or surgery | Control, Veterans with Post-traumatic Stress Disorder (PTSD) |
| Cold Pressor Test (CPT)Subjects' hand will be submerged in cold water (~0-1°C) up to the wrist for 1 minute. | Procedure or surgery | Control, Veterans with Post-traumatic Stress Disorder (PTSD) |
| Sodium Nitroprusside (SNP)Also: NitropressSubjects will receive sodium nitroprusside 100 µg, which is bolused through an antecubital intravenous catheter. | Drug | Control, Veterans with Post-traumatic Stress Disorder (PTSD) |
| PhenylephrineSubjects will receive phenylephrine 150 µg, which is bolused through an antecubital intravenous catheter 60 seconds after the sodium nitroprusside bolus | Drug | Control, Veterans with Post-traumatic Stress Disorder (PTSD) |
| LosartanAlso: CozaarLosartan will be administered as 25 mg taken orally, once a day for to 8 to 14 weeks. | Drug | Losartan |
| AtenololAlso: TenorminAtenolol will be administered as 25 mg taken orally, once a day for to 8 to 14 weeks. | Drug | Atenolol |
| Transcutaneous Vagal Nerve Stimulation (tVNS)Also: ElectroCoreTranscutaneous vagal nerve stimulation (tVNS) is administered using the gammaCore (ElectroCore) TENS device. The gammaCore device is a multi-use, hand-held, rechargeable portable device consisting of a rechargeable battery, signal generating and amplifying electronics, and two buttons to power on the device and for operator control of the stimulation intensity (range 0-40). A small amount of conductive gel is applied to the pair of stainless steel round discs on the device are placed vertically on the skin with the gel. The stimulation is increased until there is a strong vibration and slight muscle contraction in the lower face or neck (usual intensity 15-25). Then the dose 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 of treatment. Participants will be instructed on the usage of the device and will self-administer up to 4 treatments twice per day. | Device | Transcutaneous Vagal Nerve Stimulation (tVNS) |
| Sham Transcutaneous Vagal Nerve Stimulation (tVNS)A sham device that is identical to the gammaCore device will be provided to participants. Participants will be instructed on the usage of the device and will self-administer up to 4 treatments twice per day. | Device | Sham Transcutaneous Vagal Nerve Stimulation (tVNS) |
Primary outcome
Change in Muscle Sympathetic Nerve Activity (MSNA)
Time frame: Baseline, after study intervention (up to 14 weeks)
Multiunit postganglionic sympathetic nerve activity is recorded from a tungsten microelectrode inserted into the peroneal nerve with a reference microelectrode inserted in close proximity. Efferent nerve signals are amplified, filtered, rectified and integrated (time constant 0.1 s) to obtain a mean voltage display of MSNA. MSNA bursts are automatically detected using the following criteria: burst-to-noise ratio of 3:1 within a 0.5-s search window, with an average latency of 1.2-1.3 s in burst occurrence from the previous R-wave. MSNA is expressed as burst frequency measured a bursts per minute. MSNA will be examined at rest and during mental stress.
6 secondary outcomes
Change in Baroreflex Sensitivity (BRS)
Time frame: Baseline, after study intervention (up to 14 weeks)
C-reactive protein (CRP)
Time frame: Baseline, after study intervention (up to 14 weeks)
Interleukin 2 (IL-2)
Time frame: Baseline, after study intervention (up to 14 weeks)
Interleukin 6 (IL-6)
Time frame: Baseline, after study intervention (up to 14 weeks)
Angiotensin II (ATII)
Time frame: Baseline, after study intervention (up to 14 weeks)
Lipoprotein-associated Phospholipase A2 Mass (Lp-PLA2)
Time frame: Baseline, after study intervention (up to 14 weeks)
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 18 May 2026.
- 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 principal investigator
Emory University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Microneurography, Combat virtual reality video clip and Handgrip Exercise in people with Stress Disorders, Post-Traumatic, 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 17 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 18 May 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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 (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) (time frame: Baseline, after study intervention (up to 14 weeks)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 18 May 2026.