Metabolic Effects of Angiotensin-(1-7)
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18-60
SponsorVanderbilt University
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
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)
Trial design
Design model
Crossover
Treatments tested in this trial
Angiotensin-(1-7)
DrugThis 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
DrugNormal saline will be used as a placebo comparator.
Treatment groups
26 Participants
are divided into 2 treatment groupsGroup A: Angiotensin-(1-7)Experimental treatment 1 intervention
Group B: SalinePlacebo comparator 1 intervention
Trial outcomes
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.
Time frame
steady-state (time 90 to 120 minutes) during hyperinsulinemic-euglycemic clampSecondary outcomes
1
Blood Pressure
The change in blood pressure following angiotensin-(1-7) versus saline infusion.
Time frame
150 minutes2
Heart Rate
The change in heart rate following angiotensin-(1-7) versus saline infusion.
Time frame
150 minutes3
Cardiac Output
The change in cardiac output following angiotensin-(1-7) versus saline infusion.
Time frame
150 minutes4
Stroke Volume
The change in stroke volume following angiotensin-(1-7) versus saline infusion.
Time frame
150 minutesOther outcomes
1
Renin Activity
The change in plasma renin activity following angiotensin-(1-7) versus saline infusion.
Time frame
150 minutes2
Angiotensin Peptides
The change in plasma angiotensin peptides following angiotensin-(1-7) versus saline infusion.
Time frame
150 minutes3
Aldosterone
The change in plasma aldosterone following angiotensin-(1-7) versus saline infusion.
Time frame
150 minutes4
Adipokines
The change in circulating adipokines following angiotensin-(1-7) versus saline infusion.
Time frame
150 minutesSponsors and contacts
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Source ClinicalTrials.gov