Sympathetic Overactivity in Post-traumatic Stress Disorder

Not Applicable

Recruiting

• Conditions: Prehypertension; Post-traumatic Stress Disorder
• Interventions: Device: Device-Guided Breathing (DGB); Device: Transcutaneous Vagal Nerve Stimulation (tVNS); Device: Sham tVNS; Device: Sham DGB

• Registration Number: NCT01627301
• Lead Sponsor: Emory University

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.

Study Timeline

• Study First Submitted: 2012-06-21
• Study First Submitted QC: 2012-06-22
• Study First Posted: 2012-06-25
• Study Start: 2012-07
• Status Verified: 2023-09
• Last Update Submitted: 2023-09-08
• Last Update Posted: 2023-09-11
• Primary Completion: 2024-12
• Study Completion: 2024-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

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

Read More

Exclusion Criteria

• heart or vascular disease
• illicit drug use
• 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

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Device-guided Breathing (DGB)	Device-Guided Breathing (DGB)	Participants randomized to the DGB group use a device to guide their breathing to a slow breathing rate.
Transcutaneous Vagal Nerve Stimulation (tVNS)	Transcutaneous Vagal Nerve Stimulation (tVNS)	Participants randomized to use a tVNS device to deliver mild electrical stimulation to the vagal nerve.
Sham tVNS	Sham tVNS	Participants randomized to use the sham tVNS device which vibrates but does not stimulate the vagal nerve.
Sham DGB	Sham DGB	Participants randomized to the sham DGB group use a device identical to the DGB device but respiratory rates are not guided lower than the physiological rate.

Primary Outcome Measures

Name	Time	Method
Change in Muscle Sympathetic Nerve Activity (MSNA) Burst Frequency at Rest	Baseline, Week 8	MSNA is assessed with microneurography where a tungsten microelectrode inserted in the nerve records sympathetic nerve activity.
Change in Baroreflex Sensitivity (BRS) at Rest	Baseline, Week 8	Arterial baroreflex sensitivity (BRS) will be tested using pharmacologic manipulation of blood pressure at rest. BRS is assessed by measuring changes in MSNA and heart rate during arterial blood pressure changes induced by nitroprusside and phenylephrine.
Change in BRS While Under Mental Stress	Baseline, Week 8	Mental stress will be induced by having participants complete mental arithmetic and with a combat virtual reality clip. Arterial baroreflex sensitivity (BRS) will be tested using pharmacologic manipulation of blood pressure at rest and during mental stress.
Change in MSNA Burst Frequency While Under Mental Stress	Baseline, Week 8	Mental stress will be induced by having participants complete mental arithmetic and with a combat virtual reality clip.

Secondary Outcome Measures

Name	Time	Method
Endothelial Function	Baseline, Week 8	Endothelial Function will be measured using peripheral arterial tonometry.
Vascular Stiffness	Baseline, Week 8	Vascular stiffness will be measured noninvasively using pulse wave analysis and pulse wave velocity.

Trial Locations

Locations (1)

Atlanta VA Medical Center; 🇺🇸 Decatur, Georgia, United States