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Reversing Glucose and Lipid-mediated Vascular Dysfunction (REGAL)

Primary Purpose

Blood Pressure, Hypertension

Status
Recruiting
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Dextrose 20 % in 500 ML Injection
Intralipid
Saline
Ascorbic acid
Sponsored by
University of Kansas Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Blood Pressure

Eligibility Criteria

18 Years - 79 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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)

Sites / Locations

  • University of Kansas Medical CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Glucose Infusion

Lipid Infusion

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.
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.
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.
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.
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.

Secondary Outcome Measures

Full Information

First Posted
March 31, 2021
Last Updated
May 9, 2022
Sponsor
University of Kansas Medical Center
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1. Study Identification

Unique Protocol Identification Number
NCT04832009
Brief Title
Reversing Glucose and Lipid-mediated Vascular Dysfunction
Acronym
REGAL
Official Title
Reversing Glucose and Lipid-mediated Vascular Dysfunction (REGAL)
Study Type
Interventional

2. Study Status

Record Verification Date
May 2022
Overall Recruitment Status
Recruiting
Study Start Date
May 9, 2022 (Actual)
Primary Completion Date
May 9, 2023 (Anticipated)
Study Completion Date
January 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Kansas Medical Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Blood Pressure, Hypertension

7. Study Design

Primary Purpose
Other
Study Phase
Early Phase 1
Interventional Study Model
Parallel Assignment
Model Description
Comparisons of outcome variables will be made using a mixed model ANOVA.
Masking
ParticipantCare ProviderInvestigator
Masking Description
Randomized, double-blinded, parallel-design approach study.
Allocation
Randomized
Enrollment
46 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Glucose Infusion
Arm Type
Experimental
Arm Description
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.
Arm Title
Lipid Infusion
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Dextrose 20 % in 500 ML Injection
Other Intervention Name(s)
Glucose
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Intralipid
Other Intervention Name(s)
Lipid
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Saline
Other Intervention Name(s)
Placebo
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Ascorbic acid
Intervention Description
(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.
Primary Outcome Measure Information:
Title
Efficacy of Infusion of Ascorbic Acid
Description
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.
Time Frame
Baseline
Title
Efficacy of Infusion of Ascorbic Acid
Description
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.
Time Frame
30 minutes
Title
Efficacy of Infusion of Ascorbic Acid
Description
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.
Time Frame
60 minutes
Title
Efficacy of Infusion of Ascorbic Acid
Description
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.
Time Frame
90 minutes
Title
Efficacy of Infusion of Ascorbic Acid
Description
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.
Time Frame
120 minutes

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
79 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Seth W Holwerda, PhD
Phone
9729223230
Email
sholwerda@kumc.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Davina A Clonch
Phone
9132266009
Email
shoggirl@gmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Seth W. W Holwerda, PhD
Organizational Affiliation
University of Kansas Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Kansas Medical Center
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66103
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Seth W. W Holwerda
Phone
972-922-3230
Email
sholwerda@kumc.edu

12. IPD Sharing Statement

Plan to Share IPD
No

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Reversing Glucose and Lipid-mediated Vascular Dysfunction

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