Clinical trial

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

Active, not recruiting · Phase 1 · 1 countries · Registry ID NCT03318094

Active, not recruitingPhase 1Interventional

What this study is about

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.

A promising-looking record is not the same as confirmed eligibility. The study team must review the full criteria and current recruitment status.

Basic eligibility

Age18 Years to 60 Years
SexAll
Healthy volunteersAccepted
ConditionInsulin Resistance, Healthy, Obesity

Full registry 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)

Treatments and study arms

Phentolamine

Drug

Intrabrachial phentolamine will be given on the blocked day

Saline

Other

Intrabrachial saline will be given this day

Sodium Nitroprusside

Drug

Intrabrachial sodium nitroprusside will be given this day to compare with phentolamine

Primary outcomes

Contrast Enhanced-Ultrasonography (CEU)Before clamp and 15 minutes after clamp

The Primary Outcome will be the change in CEU induced by insulin during hyperinsulinemic clamp compared to baseline. To test the null hypothesis that insulin will not produce any changes in microvascular blood volume using CEU in response to α-adrenergic blockade (phentolamine) in the isolated forearm model.

Study locations

1 locations were listed when this page was built. The first 40 are shown.

Autonomic Dysfunction Center🇺🇸 Nashville, Tennessee, United States