Sympathetic-vascular Dysfunction in Obesity and Insulin Resistance (Vitamin C Study)

Sympathetic-vascular Dysfunction in Obesity and Insulin Resistance

The main purpose of research is to examine and understanding the development of hypertension in obese adults with insulin resistance. Findings from our studies will identify unique mechanisms that can be targeted to limit increases in vascular dysfunction and reduce the excessively high prevalence of hypertension and risk for cardiovascular disease (CVD).

This study is testing the health of the blood vessels and the activity of the nerves that control the blood vessels in adults with insulin resistance. The extent to which ascorbic acid (Vitamin C) improves the function of the blood vessels will be determined. The primary outcome is blood pressure, which is the result of blood vessel health and activity of the nerves, and the reduction in blood pressure that is observed with ascorbic acid.

Study Overview

• Status: Recruiting
• Conditions: Cardiovascular Diseases; Hypertension
• Intervention / Treatment: Drug: Saline; Drug: Ascorbic acid solution (American Regent Laboratories Inc.)

• Study Type: Interventional
• Enrollment (Estimated): 23
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Seth Holwerda, PhD; Phone Number: 9729223230; Email: sholwerda@kumc.edu
• Study Contact Backup: Name: Manuel Clark, MPA; Phone Number: 913-945-5763; Email: mclark16@kumc.edi

Study Locations

• United States
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • Recruiting
      • University of Kansas Medical Center
      • Contact: Davina Clonch; Phone Number: 913-226-6009; Email: dclonch@kumc.edu
      • Contact: Megan Gangwish; Phone Number: 913-444-0949; Email: mgangwish@kumc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Obese: BMI >30 m/kg2
2. Middle-aged: 35-65 years
3. Participants must be willing and able to discontinue taking any vitamin C or E supplements or omega-3 fatty acids beginning 2 weeks prior.
4. Able and willing to provide written informed consent

Exclusion Criteria:

1. Diabetes mellitus: fasting glucose < 1267 mg/dL and/or HbA1c < 6.5%
2. Currently taking a statin or antihypertension medication
3. Hyperlipidemia: Fasting triglycerides < 250 mg/dL
4. Hypertension: <130/80 mmHg
5. History of heart disease (e.g., myocardial infarction, stent)
6. History of vascular disease (e.g., bypass, stroke)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo infusion; Saline will be administered over 2 hours	Drug: Saline; Placebo (saline) will be administered
Active Comparator: Ascorbic acid infusion; Ascorbic acid solution (American Regent Laboratories Inc.) will be obtained from the KU Investigational Pharmacy located in the University of Kansas (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.	Drug: Ascorbic acid solution (American Regent Laboratories Inc.); Ascorbic acid solution (American Regent Laboratories Inc.) 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.

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.	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
• Investigators: Principal Investigator: Seth Holwerda, PhD, University of Kansas Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): June 17, 2021
• Primary Completion (Estimated): April 1, 2025
• Study Completion (Estimated): April 1, 2025

Study Registration Dates

• First Submitted: January 10, 2021
• First Submitted That Met QC Criteria: January 14, 2021
• First Posted (Actual): January 20, 2021

Study Record Updates

• Last Update Posted (Actual): October 24, 2023
• Last Update Submitted That Met QC Criteria: October 20, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hyperinsulinism; Cardiovascular Diseases; Insulin Resistance; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Protective Agents; Micronutrients; Vitamins; Antioxidants; Ascorbic Acid
• Other Study ID Numbers: STUDY00146744

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
• product manufactured in and exported from the U.S.: Yes