Role of Sympathetic Overactivity and Angiotensin II in PTSD and CV (ANG-P)

• ClinicalTrials.gov Identifier: NCT02560805
• Recruitment Status: Suspended
• First Posted: September 25, 2015
• Last Update Posted: May 5, 2020
• Sponsor: Emory University
• Information provided by (Responsible Party): Jeanie Park, Emory University

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Stress Disorders, Post-Traumatic	Procedure: Microneurography; Behavioral: Combat virtual reality video clip; Procedure: Handgrip Exercise; Procedure: Cold Pressor Test (CPT); Drug: Sodium Nitroprusside (SNP); Drug: Phenylephrine; Drug: Losartan; Drug: Atenolol	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 134 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Prevention
• Official Title: Post-Traumatic Stress Disorder and Cardiovascular Disease Risk: Role of Sympathetic Overactivity and Angiotensin II
• Study Start Date: October 2015
• Estimated Primary Completion Date: August 2021
• Estimated Study Completion Date: August 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Veterans; Subjects with post-traumatic stress disorder (PTSD) will be evaluated using microneurography, static handgrip exercise, cold pressor test, combat virtual reality video clip, and baroreflex sensitivity using sodium nitroprusside and phenylephrine. For the second phase, they will be randomized to either losartan or atenolol.	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.; Other Name: Nitropress; 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; Subjects will receive Losartan 25 mg once a day orally up to 12 weeks; Other Name: Cozaar; Drug: Atenolol; Subjects will receive Atenolol 25 mg once a day orally up to 12 weeks; Other Name: Tenormin
Experimental: Control; Healthy controls will be evaluated using microneurography, static handgrip exercise, cold pressor test, combat virtual reality video clip, and baroreflex sensitivity using sodium nitroprusside and phenylephrine.	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.; Other Name: Nitropress; Drug: Phenylephrine; Subjects will receive phenylephrine 150 µg, which is bolused through an antecubital intravenous catheter 60 seconds after the sodium nitroprusside bolus

Outcome Measures

Primary Outcome Measures :

1. Muscle sympathetic nerve activity at rest and during mental stress [ Time Frame: 12 weeks ]

Secondary Outcome Measures :

1. Change in Baroreflex sensitivity (BRS) at rest and during mental stress [ Time Frame: 12 weeks ]
2. Change in inflammatory biomarkers [ Time Frame: 12 weeks ]
   Inflammatory biomarkers will be assessed using standard assays.
3. Change in Blood Pressure [ Time Frame: 12 weeks ]
4. Change in PTSD symptoms [ Time Frame: 12 weeks ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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 as estimated glomerular filtration rate (GFR) < 60 cc/min
• hyperkalemia (serum potassium > 5 meq/dL)
• systolic blood pressure < 100 mm Hg
• diastolic blood pressure < 60 mm Hg
• heart rate < 50 beats/min
• known hypersensitivity to ARBs or beta blockers

Contacts and Locations

Locations

United States, Georgia

Atlanta VA Medical Center

Decatur, Georgia, United States, 30033

Sponsors and Collaborators

Emory University

Investigators

• Principal Investigator: Jeanie Park, MD; Emory University

More Information

• Responsible Party: Jeanie Park, Associate Professor, Emory University
• ClinicalTrials.gov Identifier: NCT02560805
• Other Study ID Numbers: IRB00082400
• First Posted: September 25, 2015
• Last Update Posted: May 5, 2020
• Last Verified: May 2020

Additional relevant MeSH terms:

Atenolol; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic; Trauma and Stressor Related Disorders; Mental Disorders; Losartan; Nitroprusside; Phenylephrine; Oxymetazoline; Anti-Arrhythmia Agents; Antihypertensive Agents; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Molecular Mechanisms of Pharmacological Action; Cardiotonic Agents; Mydriatics; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Sympathomimetics; Vasoconstrictor Agents; Nasal Decongestants; Respiratory System Agents; Adrenergic alpha-1 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Adrenergic Agents; Neurotransmitter Agents; Protective Agents; Sympatholytics