Reversing Glucose and Lipid-mediated Vascular Dysfunction

NCT04832009 | Recruiting Early Phase 1 FDA Drug

• 1 other identifier: 00147066
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Blood Pressure; Hypertension

Outcome Measures

Primary Outcomes (5)

• 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

Study Arms (2)

Glucose Infusion

EXPERIMENTAL

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; Drug: Saline; Drug: Ascorbic acid

Lipid Infusion

EXPERIMENTAL

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: Intralipid; Drug: Saline; Drug: Ascorbic acid

Interventions

Dextrose 20 % in 500 ML Injection DRUG

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.

Also known as: Glucose

Glucose Infusion

Intralipid DRUG

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.

Also known as: Lipid

Lipid Infusion

Saline DRUG

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.

Also known as: Placebo

Glucose Infusion; Lipid Infusion

Ascorbic acid DRUG

(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.

Glucose Infusion; Lipid Infusion

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• University of Kansas Medical Center: lead

Study Sites (1)

University of Kansas Medical Center

Kansas City, Kansas, 66103, United States

RECRUITING

MeSH Terms

Conditions

Hypertension

Interventions

Glucose; Injections; soybean oil, phospholipid emulsion; Lipids; Sodium Chloride; Ascorbic Acid

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Hexoses; Monosaccharides; Sugars; Carbohydrates; Drug Administration Routes; Drug Therapy; Therapeutics; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Sugar Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Hydroxy Acids

Study Officials

• Seth W. W Holwerda, PhD

  University of Kansas Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Seth W Holwerda, PhD

CONTACT

9729223230; sholwerda@kumc.edu

Davina A Clonch

CONTACT

9132266009; shoggirl@gmail.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Randomized, double-blinded, parallel-design approach study.
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Comparisons of outcome variables will be made using a mixed model ANOVA.

Study Record Dates

• First Submitted: March 31, 2021
• First Posted: April 5, 2021
• Study Start: May 9, 2022
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2027
• Last Updated: June 5, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)