Nitric Oxide Bioavailability and Early Life Stress (NO-Stress)

Study Overview
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Brief Summary
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Cardiovascular disease is the leading cause of death in the United States. Other studies have shown that stress, early in life, could be a risk factor for cardiovascular disease, later in life. This study will look at the effect of early life stressors on your cardiovascular health.

Detailed Description
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This study will have two parts involved to investigate the role that childhood SES status has on cardiovascular health. Part one: Subjects will give a blood sample which will be processed and analyzed. Flow mediated dilation (FMD) and Pulse wave velocity (PWV/PWA) will be performed at baseline and 2 hours following either a single dose oral antioxidant cocktail (1000 mg of Vitamin C, 600 IU of Vitamin E, and 600 mg of alpha-lipoic acid) or placebo on two days separated by at least 72 hours. Nitroglycerin mediated dilation (NMD, 0.4mg sub-lingual nitroglycerin spray), will be assessed at baseline. Part two: Subjects, if interested will undergo a subcutaneous gluteal/hip fat biopsy. Micro vessels will be isolated from the adipose tissue and analyzed by pressurized myography for endothelial function and nitric oxide bioavailability.

Official Title
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Effect of Low Childhood Socioeconomic Status (SES) on Adult Endothelial Function and Nitric Oxide Bioavailability in Vivo and ex Vivo

Conditions
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Cardiovascular Disease

Intervention / Treatment
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* Dietary Supplement: Antioxidant cocktail
* Other: Biopsy
* Other: Placebo
* Drug: NMD; 0.4mg sub-lingual nitroglycerin spray


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: documented childhood SES men and premenopausal women ages 18-40 lean/overweight/or obese with BMI< or equal to 39kg/m2 Exclusion Criteria: cardiovascular, renal, pulmonary, hepatic, cerebral, or metabolic,disease use medications that affect vascular tone post menopausal women have class 3 obesity or BMI over 40

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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 |
| --- | --- |
| Experimental: Antioxidant Cocktail<br>Following an overnight fast, blood samples, flow-mediated dilation, and nitroglycerin mediated dilation (NMD; 0.4mg sub-lingual nitroglycerin spray) will be performed at baseline and 2 hours following either a single dose oral antioxidant cocktail (1000 mg Vitamin C, 600 IU vitamin E, 600 mg Alpha Lipoic Acid) or placebo on two days separated by at least 72 hours. | Dietary Supplement: Antioxidant cocktail<br>* Flow-Mediated Dilation will be determined at baseline and 2 hours following acute antioxidant treatment<br>* Other names: Alpha Lipoic Acid;Other: Placebo<br>* Flow-Mediated Dilation will be determined at baseline and 2 hours following acute antioxidant treatment<br>Drug: NMD; 0.4mg sub-lingual nitroglycerin spray<br>* Nitroglycerin mediated dilation will be measured immediately following an administered 0.4mg dose of nitroglycerin spray, sub-lingual.<br>* Other names: Manufacturer: Arbor Pharmaceuticals;|
| Other: Biopsy<br>Following an overnight fast, a subcutaneous gluteal/hip fat biopsy sample will be obtained from each subject under local anesthesia, with adipose tissue ( 2x1.5x1.5cm) to be harvested and placed immediately in physiological saline solution (PSS): Small arteries, 100 to 150 um in diameter, will be dissected from the fat under a dissecting microscope, transferred to an arteriographic bath chamber, and cannulated for pressurized myography. | Other: Biopsy<br>* Under sterile conditions, a small incision (¼ - ½ inch) by the study doctor will be made and the piece of fat will be taken out. Fat tissue was chosen for this study because it is a big source of small blood vessels which we are studying<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute Change in Flow mediated dilation | Flow-Mediated Dilation will be determined at baseline and 2 hours following acute antioxidant treatment | Change from baseline (2 hours) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute Change in Biomarkers of oxidative stress | Nitrite/nitrate, antioxidant capacity, and 8-isoprostane at baseline and 2 hours following acute antioxidant treatment | Change from baseline (2 hours) | 
| Acute Change in Arterial Stiffness | Pulse wave velocity will be determined at baseline and 2 hours following acute antioxidant treatment | Change from baseline (2 hours) | 
| Acute change in Flow mediated dilation | Nitroglycerin mediated dilation will be measured immediately following an administered 0.4mg dose of nitroglycerin spray, sub-lingual. | Immediate | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Low childhood SES, Early Life Stress, Endothelial function, Flow mediated dilation, Cardiovascular disease, Subcutaneous adipose arterioles