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

• ClinicalTrials.gov Identifier: NCT02560805
• Recruitment Status: Recruiting
• First Posted: September 25, 2015
• Last Update Posted: October 17, 2019
• Sponsor: Emory University
• Information provided by (Responsible Party): Jeanie Park, Emory University

Tracking Information

• First Submitted Date: September 24, 2015
• First Posted Date: September 25, 2015
• Last Update Posted Date: October 17, 2019
• Study Start Date: October 2015
• Estimated Primary Completion Date: August 2021 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: September 24, 2015): Muscle sympathetic nerve activity at rest and during mental stress [ Time Frame: 12 weeks ]
• Original Primary Outcome Measures: Same as current
• Change History: Complete list of historical versions of study NCT02560805 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: September 24, 2015)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Role of Sympathetic Overactivity and Angiotensin II in PTSD and CV
• Official Title: Post-Traumatic Stress Disorder and Cardiovascular Disease Risk: Role of Sympathetic Overactivity and Angiotensin II
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Prevention
• Condition: Stress Disorders, Post-Traumatic

Intervention

• 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

Study Arms

• 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.
  Interventions:

  • 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
• 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.
  Interventions:

  • Procedure: Microneurography
  • Behavioral: Combat virtual reality video clip
  • Procedure: Handgrip Exercise
  • Procedure: Cold Pressor Test (CPT)
  • Drug: Sodium Nitroprusside (SNP)
  • Drug: Phenylephrine

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: September 24, 2015): 134
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: August 2021
• Estimated Primary Completion Date: August 2021 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Contacts

Contact: Melanie Jefferson, MS; 404-321-6111 ext 7040; melanie.l.jefferson@emory.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02560805
• Other Study ID Numbers: IRB00082400
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Jeanie Park, Emory University
• Study Sponsor: Emory University
• Collaborators: Not Provided

Investigators

• Principal Investigator: Jeanie Park, MD; Emory University

• PRS Account: Emory University
• Verification Date: October 2019