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

Study Overview
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Brief Summary
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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.

Official Title
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Sympathetic-vascular Dysfunction in Obesity and Insulin Resistance

Conditions
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Hypertension, Cardiovascular Diseases

Intervention / Treatment
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* Drug: Ascorbic acid solution (American Regent Laboratories Inc.)
* Drug: Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Obese: BMI >30 m/kg2 Middle-aged: 35-65 years 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: fasting glucose < 1267 mg/dL and/or HbA1c < 6.5% Currently taking a statin or antihypertension medication Hyperlipidemia: Fasting triglycerides < 250 mg/dL Hypertension: <130/80 mmHg History of heart disease (e.g., myocardial infarction, stent) History of vascular disease (e.g., bypass, stroke)

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo infusion<br>Saline will be administered over 2 hours | Drug: Saline<br>* Placebo (saline) will be administered<br>|
| Active Comparator: Ascorbic acid infusion<br>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.)<br>* 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.<br>|

What is the study measuring?
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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 |