Recruiting
Phase 1

Angiotensin-(1-7)

Sponsor:

Vanderbilt University

Code:

NCT02646475

Conditions

Obesity

Insulin Resistance

Hypertension

Metabolic Cardiovascular Syndrome

Eligibility Criteria

Sex: All

Age: 18 - 60

Healthy Volunteers: Not accepted

Interventions

Angiotensin-(1-7)

Saline

Study Details

Brief summary:

The overall purpose of this study is to learn more about the metabolic effects of angiotensin-(1-7) in the insulin resistant state associated with obesity. Pharmacologic approaches to increase angiotensin-(1-7) levels or its actions are currently in development for treatment of metabolic-related diseases such as obesity and type II diabetes, based on findings from animal studies. It is unclear if this peptide contributes to the regulation of metabolism in humans. The investigators will test if angiotensin-(1-7) infusion can improve insulin sensitivity measured by hyperinsulinemic-euglycemic clamp methods in individuals with obesity and insulin resistance. The investigators will also examine for changes in blood pressure and related hemodynamic and hormonal changes following angiotensin-(1-7) infusion.

Conditions

Obesity

Insulin Resistance

Hypertension

Metabolic Cardiovascular Syndrome

Study ID

NCT02646475

Start date

Feb, 2016

Status verified date

May, 2026

Completion date

Dec, 2029

Anticipated

Primary completion date

Dec, 2029

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 60

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Males and females of all races between 18 and 60 years of age
  • Obesity defined as body mass index between 30-40 kg/m2
  • Insulin resistance defined as homeostasis model assessment 2 insulin resistance (HOMA2-IR) score >2.2
  • Hypertension defined by two or more properly measured seated blood pressure readings >130/85 mmHg, or by use of anti-hypertensive medications. This blood pressure cutoff will allow us to include subjects with pre-hypertension.
  • Able and willing to provide informed consent

Exclusion Criteria:

  • Pregnancy or breast-feeding
  • Current smokers or history of heavy smoking (>2 packs/day)
  • History of alcohol or drug abuse
  • Morbid obesity (BMI > 40 kg/m2)
  • Previous allergic reaction to study medications
  • Evidence of type I or type II diabetes (i.e. fasting glucose >126 mg/dl, use of anti-diabetic medications)
  • Cardiovascular disease other than hypertension such as myocardial infarction within 6 months prior to enrollment, presence of angina pectoris, significant arrhythmia, congestive heart failure (LV hypertrophy acceptable), deep vein thrombosis, pulmonary embolism, second or third degree heart block, mitral valve stenosis, aortic stenosis, or hypertrophic cardiomyopathy
  • History of serious cerebrovascular disease such as cerebral hemorrhage, stroke, or transient ischemic attack
  • History or presence of immunological or hematological disorders
  • Impaired hepatic function \[aspartate amino transaminase (AST) and/or alanine amino transaminase (ALT) > 2.0 x upper limit of normal range\]
  • Impaired renal function (serum creatinine >1.5 mg/dl)
  • Anemia (hemoglobin <13.5 g/dl in males or <12.5 g/dl in females)
  • Treatment with serotonin-norepinephrine reuptake inhibitors (SNRIs) or norepinephrine transporter (NET) inhibitors
  • Treatment with phosphodiesterase 5 inhibitors
  • Treatment with anticoagulants
  • Treatment with chronic systemic glucocorticoid therapy (more than 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
  • Other factors which in the investigator's opinion would prevent the subject from completing the protocol (i.e., clinically significant abnormalities on clinical, mental examination or laboratory testing or inability to comply with protocol)

Study Design

Enrollment

26 participants

Anticipated

Allocation

Randomized

Intervention Model

Crossover

Primary purpose

Other

Interventions and Outcome Measures

Arms

experimental: Angiotensin-(1-7)

Subjects will receive intravenous infusion of three ascending doses of Angiotensin-(1-7). The doses are 4, 8, and 16 ng/kg/min. Each dose will be maintained for 10 minutes. The highest dose of Angiotensin-(1-7) will be maintained for an additional 120 minutes during the hyperinsulinemic-euglycemic clamp, for a total of 150 minutes of infusion.

placebo comparator: Saline

Subjects will receive an intravenous infusion of saline that is matched in volume to the Angiotensin-(1-7) study day. The saline infusion will also be maintained for a total of 150 minutes.

Interventions

Angiotensin-(1-7)

This is a biologically active endogenous angiotensin peptide. It may play an important role in the regulation of blood pressure by dilating blood vessels as well as a role in the regulation of insulin action.

Saline

Normal saline will be used as a placebo comparator.

Primary outcome measure

  • Whole-Body Insulin Sensitivity [ Time Frame: steady-state (time 90 to 120 minutes) during hyperinsulinemic-euglycemic clamp ]

Central Contacts and Locations

Central contacts

Cynthia Laws, MS

615-421-1994cynthia.laws@vumc.org

Locations

Vanderbilt University Medical Center

Recruiting

Nashville, Tennessee, United States, 37232

Contacts

Cynthia Laws, MS

615-421-1994cynthial.laws@vumc.org

More Information

Sponsor

Vanderbilt University

Last update posted

May 22, 2026

Last verified

May, 2026

Keywords

  • renin-angiotensin system
  • angiotensin
  • insulin resistance
  • blood pressure

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Vanderbilt University on 2026-05-22.