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Trial record 17 of 95 for:    body | Recruiting, Not yet recruiting, Available Studies | "Metabolic Syndrome X"

Metabolic Effects of Angiotensin-(1-7)

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ClinicalTrials.gov Identifier: NCT02646475
Recruitment Status : Recruiting
First Posted : January 5, 2016
Last Update Posted : August 24, 2018
Sponsor:
Information provided by (Responsible Party):
Italo Biaggioni, Vanderbilt University

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.

Condition or disease Intervention/treatment Phase
Obesity Insulin Resistance Hypertension Metabolic Cardiovascular Syndrome Drug: Angiotensin-(1-7) Drug: Saline Phase 1

Detailed 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 19 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Other
Official Title: Metabolic Effects of Angiotensin-(1-7)
Actual Study Start Date : February 2016
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.
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.
Other Names:
  • Angiotensin I (1-7)
  • Angiotensin I/II (1-7) Acetate

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.
Drug: Saline
Normal saline will be used as a placebo comparator.
Other Names:
  • normal saline
  • 0.9% sodium chloride




Primary Outcome Measures :
  1. Whole-Body Insulin Sensitivity [ Time Frame: steady-state (time 90 to 120 minutes) during hyperinsulinemic-euglycemic clamp ]
    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.


Secondary Outcome Measures :
  1. Blood Pressure [ Time Frame: 150 minutes ]
    The change in blood pressure following angiotensin-(1-7) versus saline infusion.

  2. Heart Rate [ Time Frame: 150 minutes ]
    The change in heart rate following angiotensin-(1-7) versus saline infusion.

  3. Cardiac Output [ Time Frame: 150 minutes ]
    The change in cardiac output following angiotensin-(1-7) versus saline infusion.

  4. Stroke Volume [ Time Frame: 150 minutes ]
    The change in stroke volume following angiotensin-(1-7) versus saline infusion.

  5. Systemic Vascular Resistance [ Time Frame: 150 minutes ]
    The change in systemic vascular resistance following angiotensin-(1-7) versus saline infusion.


Other Outcome Measures:
  1. Renin Activity [ Time Frame: 150 minutes ]
    The change in plasma renin activity following angiotensin-(1-7) versus saline infusion.

  2. Angiotensin Peptides [ Time Frame: 150 minutes ]
    The change in plasma angiotensin peptides following angiotensin-(1-7) versus saline infusion.

  3. Aldosterone [ Time Frame: 150 minutes ]
    The change in plasma aldosterone following angiotensin-(1-7) versus saline infusion.

  4. Adipokines [ Time Frame: 150 minutes ]
    The change in circulating adipokines following angiotensin-(1-7) versus saline infusion.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02646475


Contacts
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Contact: Kaleigh Rae, MPH 615-875-7421 kaleigh.rae@vanderbilt.edu

Locations
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United States, Tennessee
Vanderbilt University School of Medicine Recruiting
Nashville, Tennessee, United States, 37232
Contact: Kaleigh Rae, MPH    615-875-7421    kaleigh.rae@vanderbilt.edu   
Sponsors and Collaborators
Vanderbilt University
Investigators
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Principal Investigator: Italo Biaggioni, MD Vanderbilt University

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Responsible Party: Italo Biaggioni, Professor, Vanderbilt University
ClinicalTrials.gov Identifier: NCT02646475     History of Changes
Other Study ID Numbers: 151699
First Posted: January 5, 2016    Key Record Dates
Last Update Posted: August 24, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Italo Biaggioni, Vanderbilt University:
renin-angiotensin system
angiotensin
insulin resistance
blood pressure

Additional relevant MeSH terms:
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Metabolic Syndrome
Insulin Resistance
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Angiotensin I (1-7)
Angiotensin II
Angiotensinogen
Antihypertensive Agents
Vasodilator Agents
Vasoconstrictor Agents
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action