Metabolic Effects of Angiotensin-(1-7)

NCT02646475 | Recruiting Phase 1 DMC

• 1 other identifier: 151699
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

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

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Whole-Body Insulin Sensitivity

  Whole-body insulin sensitivity will be defined as the glucose infusion rate needed to maintain euglycemia during steady state (time=90 to 120 minutes) of the hyperinsulinemic-euglycemic clamp following angiotensin-(1-7) versus saline infusion. The insulin sensitivity will be corrected by body weight, lean body mass, and steady-state plasma insulin concentrations.

  steady-state (time 90 to 120 minutes) during hyperinsulinemic-euglycemic clamp

Secondary Outcomes (5)

• Blood Pressure

  150 minutes

• Heart Rate

  150 minutes

• Cardiac Output

  150 minutes

• Stroke Volume

  150 minutes

• Systemic Vascular Resistance

  150 minutes

Other Outcomes (4)

• Renin Activity

  150 minutes

• Angiotensin Peptides

  150 minutes

• Aldosterone

  150 minutes

Study Arms (2)

Angiotensin-(1-7)

EXPERIMENTAL

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.

Drug: Angiotensin-(1-7)

Saline

PLACEBO COMPARATOR

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.

Drug: Saline

Interventions

Angiotensin-(1-7) DRUG

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.

Also known as: Angiotensin I (1-7), Angiotensin I/II (1-7) Acetate

Angiotensin-(1-7)

Saline DRUG

Normal saline will be used as a placebo comparator.

Also known as: normal saline, 0.9% sodium chloride

Saline

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Vanderbilt University: lead

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

RECRUITING

MeSH Terms

Conditions

Obesity; Insulin Resistance; Hypertension; Metabolic Syndrome

Interventions

angiotensin I (1-7); Acetates; Sodium Chloride; Saline Solution

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids, Volatile; Fatty Acids; Lipids; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Alfredo Gamboa, MD

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Cynthia Laws, MS

CONTACT

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 31, 2015
• First Posted: January 5, 2016
• Study Start: February 1, 2016
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2029
• Last Updated: May 13, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)