Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT02646475
Other study ID # 151699
Secondary ID
Status Recruiting
Phase Phase 1
First received
Last updated
Start date February 2016
Est. completion date December 2026

Study information

Verified date January 2024
Source Vanderbilt University Medical Center
Contact Kaleigh Rae, MPH
Phone 615-875-7421
Email kaleigh.rae@vanderbilt.edu
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Description:

This is an outpatient study that requires a screening visit and two study days in the Vanderbilt Clinical Research Center. Subjects will be asked to stop taking any medications for high blood pressure for at least 2 weeks prior to the study. Subjects will receive intravenous angiotensin-(1-7) or saline infusion on two separate study days, with each study day lasting approximately four hours. There will be at least one week of washout between study days. On each study day, subjects will be instrumented with two intravenous catheters (one for blood sampling and one for drug infusion), arm and finger blood pressure cuffs, and sticky patches to measure heart rate throughout the study. The investigators will take baseline measurements of blood pressure and heart rate and collect blood samples. The investigators will also perform a rebreathing test to measure the heart's pumping capacity. After baseline measurements, the investigators will infuse angiotensin-(1-7) or saline for 30 minutes, with blood pressure and heart rate measured every 10 minutes. At the end of 30 minutes, blood samples will be collected and the rebreathing test will be repeated. The investigators will continue the angiotensin-(1-7) or saline infusion for an additional 2 hours while performing a hyperinsulinemic-euglycemic clamp to measure insulin sensitivity.


Recruitment information / eligibility

Status Recruiting
Enrollment 19
Est. completion date December 2026
Est. primary completion date December 2026
Accepts healthy volunteers No
Gender All
Age group 18 Years to 60 Years
Eligibility 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


Related Conditions & MeSH terms


Intervention

Drug:
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.

Locations

Country Name City State
United States Vanderbilt University School of Medicine Nashville Tennessee

Sponsors (1)

Lead Sponsor Collaborator
Vanderbilt University

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Other Renin Activity The change in plasma renin activity following angiotensin-(1-7) versus saline infusion. 150 minutes
Other Angiotensin Peptides The change in plasma angiotensin peptides following angiotensin-(1-7) versus saline infusion. 150 minutes
Other Aldosterone The change in plasma aldosterone following angiotensin-(1-7) versus saline infusion. 150 minutes
Other Adipokines The change in circulating adipokines following angiotensin-(1-7) versus saline infusion. 150 minutes
Primary 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 Blood Pressure The change in blood pressure following angiotensin-(1-7) versus saline infusion. 150 minutes
Secondary Heart Rate The change in heart rate following angiotensin-(1-7) versus saline infusion. 150 minutes
Secondary Cardiac Output The change in cardiac output following angiotensin-(1-7) versus saline infusion. 150 minutes
Secondary Stroke Volume The change in stroke volume following angiotensin-(1-7) versus saline infusion. 150 minutes
Secondary Systemic Vascular Resistance The change in systemic vascular resistance following angiotensin-(1-7) versus saline infusion. 150 minutes
See also
  Status Clinical Trial Phase
Recruiting NCT04101669 - EndoBarrier System Pivotal Trial(Rev E v2) N/A
Recruiting NCT04243317 - Feasibility of a Sleep Improvement Intervention for Weight Loss and Its Maintenance in Sleep Impaired Obese Adults N/A
Terminated NCT03772886 - Reducing Cesarean Delivery Rate in Obese Patients Using the Peanut Ball N/A
Completed NCT03640442 - Modified Ramped Position for Intubation of Obese Females. N/A
Completed NCT04506996 - Monday-Focused Tailored Rapid Interactive Mobile Messaging for Weight Management 2 N/A
Recruiting NCT06019832 - Analysis of Stem and Non-Stem Tibial Component N/A
Active, not recruiting NCT05891834 - Study of INV-202 in Patients With Obesity and Metabolic Syndrome Phase 2
Active, not recruiting NCT05275959 - Beijing (Peking)---Myopia and Obesity Comorbidity Intervention (BMOCI) N/A
Recruiting NCT04575194 - Study of the Cardiometabolic Effects of Obesity Pharmacotherapy Phase 4
Completed NCT04513769 - Nutritious Eating With Soul at Rare Variety Cafe N/A
Withdrawn NCT03042897 - Exercise and Diet Intervention in Promoting Weight Loss in Obese Patients With Stage I Endometrial Cancer N/A
Completed NCT03644524 - Heat Therapy and Cardiometabolic Health in Obese Women N/A
Recruiting NCT05917873 - Metabolic Effects of Four-week Lactate-ketone Ester Supplementation N/A
Active, not recruiting NCT04353258 - Research Intervention to Support Healthy Eating and Exercise N/A
Completed NCT04507867 - Effect of a NSS to Reduce Complications in Patients With Covid-19 and Comorbidities in Stage III N/A
Recruiting NCT03227575 - Effects of Brisk Walking and Regular Intensity Exercise Interventions on Glycemic Control N/A
Completed NCT01870947 - Assisted Exercise in Obese Endometrial Cancer Patients N/A
Recruiting NCT05972564 - The Effect of SGLT2 Inhibition on Adipose Inflammation and Endothelial Function Phase 1/Phase 2
Recruiting NCT06007404 - Understanding Metabolism and Inflammation Risks for Diabetes in Adolescents
Recruiting NCT05371496 - Cardiac and Metabolic Effects of Semaglutide in Heart Failure With Preserved Ejection Fraction Phase 2