Autonomic Blockade and Endogenous Glucose Production

• Status: Withdrawn
• Trial end date: 2024-12-31
• Target enrollment: 0
• Participant gender: All

Summary

The investigators will test the null hypothesis that there will be no changes in the insulin-mediated suppression of endogenous glucose production (EGP) in response to autonomic blockade. To test this hypothesis, the investigators propose to determine the role of the autonomic nervous system in hepatic insulin resistance.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Vanderbilt University Medical Center
• Treatments: Insulin; Trimethaphan; Trimethaphan camsylate

Criteria

Inclusion Criteria:

• Males and females of all races between 18 and 60 years of age

• Hypertension defined by two or more properly measured seated blood pressure readings >130/85 mmHg or currently on antihypertensive medication. This will allow us to include subjects with "pre-hypertension."

• Obesity will be defined as having a body mass index (BMI) ≥ 30 kg/m2.

• Insulin resistance will be defined as a HOMA2 IR index ≥1.6

• 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

• 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 renal function

• Anemia

• 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, inability to find IV access)