Metabolic Effects of Angiotensin-(1-7)
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 Start (Actual) February 2016
🗓️ Primary Completion (Estimated) December 2026
✅ Study Completion (Estimated) December 2026
👥 Enrollment (Estimated) 19
🔬 Study Type INTERVENTIONAL
📊 Phase PHASE1
Locations:
📍 Nashville, Tennessee, United States

📋 Eligibility Criteria

Description

    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)
Ages Eligible for Study: 18 Years to 60 Years (ADULT)
Sexes Eligible for Study: ALL
Accepts Healthy Volunteers: No

🗓️ Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

  • First Submitted 31 December 2015
  • First Submitted that Met QC Criteria 31 December 2015
  • First Posted 5 January 2016

Study Record Updates

  • Last Update Submitted that Met QC Criteria 30 January 2024
  • Last Update Posted 1 February 2024
  • Last Verified January 2024