Role of Sympathetic Overactivity and Angiotensin II in PTSD and CV

ConditionStress Disorders, Post-Traumatic

Trial statusRecruiting

Trial phasePhase 2

Trial typeInterventional

Biological sexAll

Age18-65

SponsorEmory University

About this trial

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.

Eligibility criteria

This trial accepts healthy volunteers

Qualifiers

veterans ages 18-65 years old with PTSD and without PTSD (controls) matched for age, gender, and race.

Disqualifiers

pregnancy

hypertension

diabetes

heart or vascular disease

Trial design

Design model

Parallel

Treatments tested in this trial

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

Treatment groups

134 Participants

are divided into 6 treatment groups

Treatment groups

See each treatment group below.

Group A: Veterans with Post-traumatic Stress Disorder (PTSD)Experimental treatment 6 interventions

Group B: ControlExperimental treatment 6 interventions

Group C: LosartanExperimental treatment 1 intervention

Group D: AtenololActive comparator 1 intervention

Group E: Transcutaneous Vagal Nerve Stimulation (tVNS)Experimental treatment 1 intervention

Group F: Sham Transcutaneous Vagal Nerve Stimulation (tVNS)Sham comparator 1 intervention

Trial outcomes

Primary outcomes

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.

Time frame