Reversing Glucose and Lipid-mediated Vascular Dysfunction (REGAL)

Reversing Glucose and Lipid-mediated Vascular Dysfunction (REGAL)

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.

Study Overview

• Status: Recruiting
• Conditions: Hypertension; Blood Pressure
• Intervention / Treatment: Drug: Dextrose 20 % in 500 ML Injection; Drug: Saline; Drug: Ascorbic acid; Drug: Intralipid

Detailed 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.

• Study Type: Interventional
• Enrollment (Anticipated): 46
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Seth W Holwerda, PhD; Phone Number: 9729223230; Email: sholwerda@kumc.edu
• Study Contact Backup: Name: Davina A Clonch; Phone Number: 9132266009; Email: shoggirl@gmail.com

Study Locations

• United States
  • Kansas
    • Kansas City, Kansas, United States, 66103
      • Recruiting
      • University of Kansas Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Glucose Infusion; Hyperglycemia (glucose infusion) will receive an I.V. Glucose infusion with a co-infusion of ascorbic acid or placebo at your visit 2 and the alternative treatment of ascorbic acid or placebo will be given on the subsequent study visit 3.	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.; Other Names: Glucose; Drug: 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.; Other Names: Placebo; Drug: 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.
Experimental: Lipid Infusion; Hyperlipidemia (lipid infusion) will receive an I.V. Lipid infusion with a co-infusion of ascorbic acid or placebo at your visit 2 and the alternative treatment of ascorbic acid or placebo will be given on the subsequent study visit 3.	Drug: 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.; Other Names: Placebo; Drug: 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.; Drug: 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.; Other Names: Lipid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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

Collaborators and Investigators

• Sponsor: University of Kansas Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): May 9, 2022
• Primary Completion (Anticipated): May 9, 2023
• Study Completion (Anticipated): January 1, 2024

Study Registration Dates

• First Submitted: March 31, 2021
• First Submitted That Met QC Criteria: April 2, 2021
• First Posted (Actual): April 5, 2021

Study Record Updates

• Last Update Posted (Actual): May 16, 2022
• Last Update Submitted That Met QC Criteria: May 9, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Protective Agents; Micronutrients; Vitamins; Antioxidants; Pharmaceutical Solutions; Parenteral Nutrition Solutions; Fat Emulsions, Intravenous; Soybean oil, phospholipid emulsion; Ascorbic Acid
• Other Study ID Numbers: 00147066

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No