Role of Sympathetic Overactivity and Angiotensin II in PTSD and CV

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.

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.

What is a clinical trial?

A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.

Is it safe to participate?

Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.

Will I be compensated?

Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.

Will I receive a placebo instead of treatment?

When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.

Can I leave a trial if I change my mind?

Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.

How long does a clinical trial last?

Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.