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Angiotensin 1-7 in Obesity Hypertension

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ClinicalTrials.gov Identifier: NCT03604289
Recruitment Status : Recruiting
First Posted : July 27, 2018
Last Update Posted : June 30, 2020
Sponsor:
Collaborator:
American Heart Association
Information provided by (Responsible Party):
Amy Arnold, Milton S. Hershey Medical Center

Brief Summary:
The purpose of this study is to find out if the investigational drug angiotensin-(1-7) improves cardiovascular health in patients with obesity and high blood pressure.

Condition or disease Intervention/treatment Phase
Obesity Hypertension Drug: Angiotensin-(1-7) Drug: Saline Early Phase 1

Detailed Description:
Obesity is a major public health concern that greatly increases risk for developing cardiovascular disease. Importantly, obesity is associated with endothelial dysfunction and elevated sympathetic tone, vascular and autonomic derangements known to elevate blood pressure and increase cardiovascular risk. The renin-angiotensin system may explain cardiovascular complications in obesity. Angiotensin-(1-7) is a beneficial hormone that is reduced in obesity and restoration of this hormone improves endothelial function and reduces sympathetic activity in animal models, which may contribute to its blood pressure-lowering effects. The investigators will test the hypothesis that angiotensin-(1-7) improves cardiovascular function in humans with obesity hypertension. This hypothesis will be tested in a randomized, double blind, placebo-controlled crossover study. The investigators will measure the effects of acute intravenous angiotensin-(1-7) infusion on endothelial-mediated vasodilation in the brachial and coronary arteries and on blood pressure and muscle sympathetic nerve activity with direct microneurography recordings in obese hypertensive humans.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Cardiovascular Effects of Angiotensin 1-7 in Obesity Hypertension
Actual Study Start Date : April 1, 2019
Estimated Primary Completion Date : June 2022
Estimated Study Completion Date : June 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Angiotensin-(1-7)
Participants receive intravenous angiotensin-(1-7) at one study visit for 100 minutes total. Angiotensin-(1-7) will be given in escalating doses of 2ng/kg/min, 4ng/kg/min, and 8ng/kg/min. Each of these doses will be infused for 10 minutes. Following the dose escalation, angiotensin-(1-7) will be given at 8ng/kg/min for an additional 70 minutes. Infusion rates will be calculated for each patient based on body mass.
Drug: Angiotensin-(1-7)
This is a biologically active endogenous angiotensin peptide that may play an important role in regulation of blood pressure.
Other Name: Angiotensin I/II (1-7) Acetate

Placebo Comparator: Saline
Participants receive intravenous saline at one study visit for 100 minutes total. The volume of saline will match the volume of angiotensin-(1-7) infused. Infusion rates will be calculated for each patient based on body mass. Saline will be given in escalating doses for 10 minutes each and then held for 70 minutes at the highest dose.
Drug: Saline
Saline will be used as the placebo comparator
Other Names:
  • Normal saline
  • 0.9% sodium chloride




Primary Outcome Measures :
  1. Change in brachial artery diameter with reactive hyperemia [ Time Frame: 15 minutes including baseline, cuff inflation, and reactive hyperemia ]
    A blood pressure cuff will be inflated to a suprasystolic pressure for 5 minutes then deflated. Brachial artery diameter will be measured continuously before, during, and after cuff inflation using duplex ultrasound.


Secondary Outcome Measures :
  1. Heart Rate Variability [ Time Frame: 30 minutes ]
    Resting heart rate variability will be calculated from baseline blood pressure recordings

  2. Circulating catecholamines [ Time Frame: 5 minutes ]
    circulating catecholamines will be measured from blood samples

  3. Change in coronary blood velocity to the cold pressor test [ Time Frame: 20 minutes ]
    Coronary blood velocity will be measured using duplex ultrasound before, during, and after cold pressor test (hand in ice water for 2 minutes)

  4. Change in systolic and diastolic blood pressure to the cold pressor test [ Time Frame: 20 minutes ]
    Blood pressure will be measured continuously with a finger cuff before, during, and after the cold pressor test.

  5. Change in muscle sympathetic nerve activity to the cold pressor test [ Time Frame: 20 minutes ]
    Muscle sympathetic nerve activity will be measured using peroneal nerve microneurography before, during, and after the cold pressor test.



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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Men and women of all races
  • Capable of giving informed consent
  • Age 18-60 years
  • Body mass index (BMI) between 30-40 kg/m2
  • Hypertension defined as two or more seated blood pressure readings >130/80 mmHg or use of anti-hypertensive medications
  • Satisfactory history and physical exam

Exclusion Criteria:

  • Age ≤ 17 or ≥ 61 years
  • Pregnant or nursing women
  • Decisional impairment
  • Prisoners
  • Alcohol or drug abuse
  • Current smokers
  • Highly trained athletes
  • Subjects with >5% weight change in the past 3 months
  • Evidence of type I or type II diabetes (fasting glucose > 126 mg/dL or use of anti-diabetic medications)
  • History of serious cardiovascular disease (e.g. myocardial infarction within 6 months, symptomatic coronary artery disease, presence of angina pectoris, significant arrhythmia, congestive heart failure, deep vein thrombosis, pulmonary embolism, second or third degree heart block, mitral valve stenosis, aortic stenosis, hypertrophic cardiomyopathy) or cerebrovascular disease (e.g. cerebral hemorrhage, stroke, transient Ischemic attack).
  • History or presence of immunological or hematological disorders
  • Impaired hepatic function (AST or ALT levels >2 times upper limit of normal range)
  • Impaired renal function (serum creatinine >2.0 mg/dl)
  • Anemia
  • Treatment with serotonin-norepinephrine reuptake inhibitors (SNRIs) or norepinephrine transporter (NET) inhibitors
  • Treatment with phosphodiesterase-5 inhibitors
  • Treatment with anticoagulants (e.g. warfarin)
  • Treatment with chronic systemic glucocorticoid therapy (>7 consecutive days in 1 month)
  • Treatment with any investigational drug in the 1-month preceding the study
  • Inability to give, or withdraw, informed consent

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03604289


Contacts
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Contact: Aimee C. Caufman, BSN 7175311617 acauffman@pennstatehealth.psu.edu

Locations
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United States, Pennsylvania
Penn State College of Medicine Recruiting
Hershey, Pennsylvania, United States, 17033
Contact: Amy C Arnold, PhD         
Sponsors and Collaborators
Amy Arnold
American Heart Association
Investigators
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Principal Investigator: Amy C Arnold, Ph.D. Penn State College of Medicine
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Responsible Party: Amy Arnold, Assistant Professor, Milton S. Hershey Medical Center
ClinicalTrials.gov Identifier: NCT03604289    
Other Study ID Numbers: STUDY00008170
18POST33960087 ( Other Grant/Funding Number: American Heart Association )
First Posted: July 27, 2018    Key Record Dates
Last Update Posted: June 30, 2020
Last Verified: June 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Amy Arnold, Milton S. Hershey Medical Center:
angiotensin-1-7
Additional relevant MeSH terms:
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Hypertension
Obesity
Vascular Diseases
Cardiovascular Diseases
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms
Angiotensin I (1-7)
Antihypertensive Agents
Vasodilator Agents