Study detail

RecruitingPhase 2

Post-Traumatic Stress Disorder and Cardiovascular Disease Risk: Role of Sympathetic Overactivity and Angiotensin II

Emory University

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. 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.

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 lif…

Eligibility

Age range: 18–65 years
Sex: All
Healthy volunteers: Yes

Detailed criteria

Inclusion Criteria: * veterans ages 18-65 years old with PTSD and without PTSD (controls) matched for age, gender, and race. Exclusion Criteria: * pregnancy * hypertension * diabetes * heart or vascular disease * illicit drug use * excessive alcohol use (\>2 drinks per day) * 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…

Interventions

Procedure
Microneurography
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).
Behavioral
Combat virtual reality video clip
Subjects will watch a video clip of combat on a computer screen or wearing video goggles.
Procedure
Handgrip Exercise
Subjects will squeeze a hand dynamometer intermittently.
Procedure
Cold Pressor Test (CPT)
Subjects' hand will be submerged in cold water (\~0-1°C) up to the wrist for 1 minute.
Drug
Sodium Nitroprusside (SNP)
Subjects will receive sodium nitroprusside 100 µg, which is bolused through an antecubital intravenous catheter.
Drug
Phenylephrine
Subjects will receive phenylephrine 150 µg, which is bolused through an antecubital intravenous catheter 60 seconds after the sodium nitroprusside bolus
Drug
Losartan
Losartan will be administered as 25 mg taken orally, once a day for to 8 to 14 weeks.
Drug
Atenolol
Atenolol will be administered as 25 mg taken orally, once a day for to 8 to 14 weeks.
Device
Transcutaneous Vagal Nerve Stimulation (tVNS)
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.
Device
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.

Location

Atlanta VA Medical Center
Decatur, Georgia

Summary

Description

Eligibility

Age range

18–65 years

Sex

All

Healthy volunteers

Yes

Detailed criteria

Interventions

Procedure

Microneurography

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).

Behavioral

Combat virtual reality video clip

Subjects will watch a video clip of combat on a computer screen or wearing video goggles.

Procedure

Handgrip Exercise

Subjects will squeeze a hand dynamometer intermittently.

Procedure

Cold Pressor Test (CPT)

Subjects' hand will be submerged in cold water (\~0-1°C) up to the wrist for 1 minute.

Drug

Sodium Nitroprusside (SNP)

Subjects will receive sodium nitroprusside 100 µg, which is bolused through an antecubital intravenous catheter.

Drug

Phenylephrine

Subjects will receive phenylephrine 150 µg, which is bolused through an antecubital intravenous catheter 60 seconds after the sodium nitroprusside bolus

Drug

Losartan

Losartan will be administered as 25 mg taken orally, once a day for to 8 to 14 weeks.

Drug

Atenolol

Atenolol will be administered as 25 mg taken orally, once a day for to 8 to 14 weeks.

Device

Transcutaneous Vagal Nerve Stimulation (tVNS)

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.

Device

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.