Role of Sympathetic Vasoconstriction on Insulin-Mediated Microvascular Recruitment and Glucose Uptake in Obesity

• Status: Recruiting
• Trial end date: 2025-11-30
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to better understand the contribution of sympathetic vasoconstriction to impaired insulin-mediated vasodilation and subsequently insulin-mediated glucose uptake. The investigators will test the hypothesis that removal of sympathetic vasoconstriction can result in improvement in insulin-mediated vasodilation and subsequently sensitivity to insulin-mediated glucose uptake.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Vanderbilt University Medical Center
• Treatments: Adrenergic alpha-Antagonists; Adrenergic Antagonists; Nitroprusside; Phentolamine

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 >1.6 (never diagnosed or treated type 2 diabetic), or being a well-controlled type 2 diabetic on metformin only.

• Able and willing to provide informed consent

Exclusion Criteria:

• Pregnancy or breastfeeding

• 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 diabetes.

• 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)

• Moderate to severe anemia (hemoglobin <11 g/dl)

• 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)