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Angiotensin 1-7 in Obesity Hypertension

Primary Purpose

Obesity, Hypertension

Status
Recruiting
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Angiotensin-(1-7)
Saline
Sponsored by
Amy Arnold
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Obesity focused on measuring angiotensin-1-7

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Penn State College of MedicineRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Angiotensin-(1-7)

Saline

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Change in brachial artery diameter with 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

Heart Rate Variability
Resting heart rate variability will be calculated from baseline blood pressure recordings
Circulating catecholamines
circulating catecholamines will be measured from blood samples
Change in coronary blood velocity to the cold pressor test
Coronary blood velocity will be measured using duplex ultrasound before, during, and after cold pressor test (hand in ice water for 2 minutes)
Change in systolic and diastolic blood pressure to the cold pressor test
Blood pressure will be measured continuously with a finger cuff before, during, and after the cold pressor test.
Change in muscle sympathetic nerve activity to the cold pressor test
Muscle sympathetic nerve activity will be measured using peroneal nerve microneurography before, during, and after the cold pressor test.

Full Information

First Posted
July 19, 2018
Last Updated
May 1, 2023
Sponsor
Amy Arnold
Collaborators
American Heart Association
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1. Study Identification

Unique Protocol Identification Number
NCT03604289
Brief Title
Angiotensin 1-7 in Obesity Hypertension
Official Title
Cardiovascular Effects of Angiotensin 1-7 in Obesity Hypertension
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 1, 2019 (Actual)
Primary Completion Date
December 2024 (Anticipated)
Study Completion Date
December 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Amy Arnold
Collaborators
American Heart Association

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Obesity, Hypertension
Keywords
angiotensin-1-7

7. Study Design

Primary Purpose
Basic Science
Study Phase
Early Phase 1
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
24 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Angiotensin-(1-7)
Arm Type
Experimental
Arm Description
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.
Arm Title
Saline
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Angiotensin-(1-7)
Other Intervention Name(s)
Angiotensin I/II (1-7) Acetate
Intervention Description
This is a biologically active endogenous angiotensin peptide that may play an important role in regulation of blood pressure.
Intervention Type
Drug
Intervention Name(s)
Saline
Other Intervention Name(s)
Normal saline, 0.9% sodium chloride
Intervention Description
Saline will be used as the placebo comparator
Primary Outcome Measure Information:
Title
Change in brachial artery diameter with reactive hyperemia
Description
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.
Time Frame
15 minutes including baseline, cuff inflation, and reactive hyperemia
Secondary Outcome Measure Information:
Title
Heart Rate Variability
Description
Resting heart rate variability will be calculated from baseline blood pressure recordings
Time Frame
30 minutes
Title
Circulating catecholamines
Description
circulating catecholamines will be measured from blood samples
Time Frame
5 minutes
Title
Change in coronary blood velocity to the cold pressor test
Description
Coronary blood velocity will be measured using duplex ultrasound before, during, and after cold pressor test (hand in ice water for 2 minutes)
Time Frame
20 minutes
Title
Change in systolic and diastolic blood pressure to the cold pressor test
Description
Blood pressure will be measured continuously with a finger cuff before, during, and after the cold pressor test.
Time Frame
20 minutes
Title
Change in muscle sympathetic nerve activity to the cold pressor test
Description
Muscle sympathetic nerve activity will be measured using peroneal nerve microneurography before, during, and after the cold pressor test.
Time Frame
20 minutes

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Aimee C. Caufman, BSN
Phone
7175311617
Email
acauffman@pennstatehealth.psu.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Amy C Arnold, Ph.D.
Organizational Affiliation
Penn State College of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Penn State College of Medicine
City
Hershey
State/Province
Pennsylvania
ZIP/Postal Code
17033
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Amy C Arnold, PhD

12. IPD Sharing Statement

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Angiotensin 1-7 in Obesity Hypertension

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