RecruitingEarly Phase 1NCT04832009

Reversing Glucose and Lipid-mediated Vascular Dysfunction

Reversing Glucose and Lipid-mediated Vascular Dysfunction (REGAL)

Sponsor

University of Kansas Medical Center

Enrollment

46 participants

Start Date

May 9, 2022

Study Type

INTERVENTIONAL

Conditions

Hypertension Blood Pressure

Summary

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.

Eligibility

Min Age: 18 YearsMax Age: 79 Years

Inclusion Criteria7

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 Criteria6

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)

Interventions

DRUGDextrose 20 % in 500 ML Injection

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.

DRUGIntralipid

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.

DRUGSaline

Saline will be obtained from the Investigational Pharmacy located in the KU Clinical Research Center where studies take place. Will be administered via antecubital vein at 75 to 150 mL/hour for 2 hours.

DRUGAscorbic acid

(ASCOR) will be obtained from the KU Investigational Pharmacy located in the KU Clinical Research Center where studies will take place. A priming bolus of 0.06 g ascorbic acid/kg fat free mass (FFM) dissolved in 100 mL of saline will be infused intravenously at 5 mL/min for 20 minutes, followed immediately by a "drip-infusion" of 0.02 g/kg FFM dissolved in 30 mL of saline administered over 2 hours at 0.5 mL/min. The KU Investigational Pharmacy will randomize ascorbic acid or placebo (saline) for each participant.