Clinical trial NCT01627301: Sympathetic Overactivity in Post-traumatic Stress Disorder
Official title: Mechanisms of Sympathetic Overactivity in Post-traumatic Stress Disorder
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Post-traumatic Stress Disorder
Prehypertension
Lead sponsor: Emory University
Sponsor class: OTHER
Collaborators: name: US Department of Veterans Affairs
First posted: 2012-06-25
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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. 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.

Eligibility criteria: Inclusion Criteria:

* Prehypertensive and normotensive veterans with PTSD, and prehypertensive and normotensive veterans without PTSD (controls)

Exclusion Criteria:

* 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

Primary outcomes:
measure: Change in Muscle Sympathetic Nerve Activity (MSNA) Burst Frequency at Rest
timeFrame: Baseline, Week 8
measure: Change in Baroreflex Sensitivity (BRS) at Rest
timeFrame: Baseline, Week 8
measure: Change in MSNA Burst Frequency While Under Mental Stress
timeFrame: Baseline, Week 8
measure: Change in BRS While Under Mental Stress
timeFrame: Baseline, Week 8
Secondary outcomes:
measure: Endothelial Function
timeFrame: Baseline, Week 8
measure: Vascular Stiffness
timeFrame: Baseline, Week 8
Other outcomes:
Locations:
city: Decatur
country: United States
facility: Atlanta VA Medical Center
state: Georgia
Study officials:
affiliation: Emory University and the Atlanta VA Medical Center
name: Jeanie Park, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.