Reversing Glucose and Lipid-mediated Vascular Dysfunction

Hypertension Clinical Trial

— REGAL  

Official title:

Reversing Glucose and Lipid-mediated Vascular Dysfunction (REGAL)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04832009
• Other study ID #: 00147066
• Status: Recruiting
• Phase: Early Phase 1
• Start date: May 9, 2022
• Est. completion date: January 1, 2024

Study information

• Verified date: May 2022
• Source: University of Kansas Medical Center
• Contact: Seth W Holwerda, PhD
• Phone: 9729223230
• Email: sholwerda[@]kumc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 46
• Est. completion date: January 1, 2024
• Est. primary completion date: May 9, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 79 Years

Eligibility

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)

Related Conditions & MeSH terms

• Blood Pressure
• Hypertension

Intervention

Drug:
• Dextrose 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.
• Intralipid
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
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.
• Ascorbic 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.

Locations

Country	Name	City	State
United States	University of Kansas Medical Center	Kansas City	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
University of Kansas Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Efficacy of Infusion of Ascorbic Acid	The difference in sympathetic-vascular transduction (mmHg) between ascorbic acid and placebo infusion will be taken as a measure of the modulation of SVT by oxidative stress.	Baseline
Primary	Efficacy of Infusion of Ascorbic Acid	The difference in sympathetic-vascular transduction (mmHg) between ascorbic acid and placebo infusion will be taken as a measure of the modulation of SVT by oxidative stress.	30 minutes
Primary	Efficacy of Infusion of Ascorbic Acid	The difference in sympathetic-vascular transduction (mmHg) between ascorbic acid and placebo infusion will be taken as a measure of the modulation of SVT by oxidative stress.	60 minutes
Primary	Efficacy of Infusion of Ascorbic Acid	The difference in sympathetic-vascular transduction (mmHg) between ascorbic acid and placebo infusion will be taken as a measure of the modulation of SVT by oxidative stress.	90 minutes
Primary	Efficacy of Infusion of Ascorbic Acid	The difference in sympathetic-vascular transduction (mmHg) between ascorbic acid and placebo infusion will be taken as a measure of the modulation of SVT by oxidative stress.	120 minutes