Reversing Glucose and Lipid-mediated Vascular Dysfunction

Early Phase 1RecruitingNCT04832009

University of Kansas Medical Center46 enrolled

Overview

The purpose of our study is to understand the extent to which the blood vessels are affected by glucose and fat (lipids) in lean healthy adults and if these changes in the blood vessels contribute to the development of high blood pressure.

Hypertension, obesity, and insulin resistance are associated with elevated muscle sympathetic nerve activity (MSNA), which is important for blood pressure regulation. The measurement of MSNA is safely performed in humans using the microneurographic technique that involves recording sympathetic nerve activity projecting to skeletal muscle using a small microelectrode at the peroneal nerve near the knee. The health of your blood vessels will be tested in this study, in addition to the activity of the nerves that control the blood vessels. The function of the nerves and blood vessels can be diminished by high blood glucose and lipids, and we will test the ability of a well-known antioxidant, ascorbic acid (vitamin C), to restore the function of the nerves and blood vessels.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

OTHER

Masking

TRIPLE

Enrollment

Conditions

Blood Pressure Hypertension

Interventions

Dextrose 20 % in 500 ML InjectionDRUG

Dextrose (20% intravenous solution) will be obtained from the Investigational Pharmacy located in the KU Clinical Research Center where studies take place. After fasting for at least 8 hours, dextrose will be administered via antecubital vein at a standard rate of 4 mg/kg/min for 2 hours.

IntralipidDRUG

Intralipid ® 20% will be obtained from the Investigational Pharmacy located in the KU Clinical Research Center where studies take place. After fasting for at least 8 hours, Intralipid ® 20% will be administered via antecubital vein at 0.75 mL/min for 2 hours Increases in circulating markers of oxidative stress peak within 2 hours of Intralipid ® 20% infusion in healthy adults (42). An initial heparin bolus of 1000 UL followed by 200 U/hr infusion will be included to activate endothelial lipoprotein lipase and accelerate hydrolysis of fatty acids.

Saline

Eligibility

Sex: ALLMin age: 18 YearsMax age: 79 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Lean: BMI \< 25 kg/m * Normal insulin sensitivity: (calculation based on fasting glucose and insulin concentrations in blood) * Middle-aged: 18-79 years * Blood pressure: \< 140 (systolic) and \< 90 mmHg (diastolic * Weight stable (+/- 5 lbs) for the previous 3 months * Participants must be willing and able to discontinue taking any vitamin C or E supplements or omega-3 fatty acids beginning 2 weeks prior. * Able and willing to provide written informed consent Exclusion Criteria: * Diabetes mellitus Type I or Type II: fasting glucose \< 126 mg/dL and/or HbA1c \< 6.5% * Current smoker or History of smoking in the past 3 months. * Hyperlipidemia: Fasting triglycerides \< 250 mg/dL * Hypertension: \>130/80 mmHg * History of heart disease (e.g., myocardial infarction, stent, heart attack, stroke, heart failure, valvular heart disease, cardiomyopathy) * History of vascular disease (e.g., bypass, stroke)

Locations (1)

University of Kansas Medical Center

Kansas City, Kansas, United States

RECRUITING