Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Reversing Glucose and Lipid-mediated Vascular Dysfunction (REGAL)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04832009
Recruitment Status : Not yet recruiting
First Posted : April 5, 2021
Last Update Posted : September 29, 2021
Sponsor:
Information provided by (Responsible Party):
Seth Holwerda PhD, University of Kansas Medical Center

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
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.

Condition or disease Intervention/treatment Phase
Blood Pressure Hypertension Drug: Dextrose 20 % in 500 ML Injection Drug: Intralipid Drug: Saline Drug: Ascorbic acid Early Phase 1

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 Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 46 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Comparisons of outcome variables will be made using a mixed model ANOVA.
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description: Randomized, double-blinded, parallel-design approach study.
Primary Purpose: Other
Official Title: Reversing Glucose and Lipid-mediated Vascular Dysfunction (REGAL)
Estimated Study Start Date : January 1, 2022
Estimated Primary Completion Date : January 1, 2023
Estimated Study Completion Date : January 1, 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Vitamin C
Drug Information available for: Dextrose

Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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 Name: 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 Name: 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: 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 Name: Lipid

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 Name: 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.


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. Efficacy of Infusion of Ascorbic Acid [ Time Frame: Baseline ]
    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.

  2. Efficacy of Infusion of Ascorbic Acid [ Time Frame: 30 minutes ]
    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.

  3. Efficacy of Infusion of Ascorbic Acid [ Time Frame: 60 minutes ]
    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.

  4. Efficacy of Infusion of Ascorbic Acid [ Time Frame: 90 minutes ]
    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.

  5. Efficacy of Infusion of Ascorbic Acid [ Time Frame: 120 minutes ]
    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.


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 79 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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)
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04832009


Contacts
Layout table for location contacts
Contact: Seth W Holwerda, PhD 9729223230 sholwerda@kumc.edu
Contact: Davina A Clonch 9132266009 shoggirl@gmail.com

Locations
Layout table for location information
United States, Kansas
University of Kansas Medical Center
Kansas City, Kansas, United States, 66103
Sponsors and Collaborators
University of Kansas Medical Center
Investigators
Layout table for investigator information
Principal Investigator: Seth W. W Holwerda, PhD University of Kansas Medical Center
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Layout table for additonal information
Responsible Party: Seth Holwerda PhD, Principal Investigator, University of Kansas Medical Center
ClinicalTrials.gov Identifier: NCT04832009    
Other Study ID Numbers: 00147066
First Posted: April 5, 2021    Key Record Dates
Last Update Posted: September 29, 2021
Last Verified: September 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Hypertension
Vascular Diseases
Cardiovascular Diseases
Ascorbic Acid
Soybean oil, phospholipid emulsion
Antioxidants
Molecular Mechanisms of Pharmacological Action
 Protective Agents
Physiological Effects of Drugs
Vitamins
Micronutrients
Fat Emulsions, Intravenous
Parenteral Nutrition Solutions
Pharmaceutical Solutions