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

Sponsor

Augusta University (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT02115724

Collaborator

National Heart, Lung, and Blood Institute (NHLBI) (NIH)

Enrollment

Location

Arms

117

Duration (Months)

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Cardiovascular Disease	Dietary Supplement: Antioxidant cocktail Other: Biopsy Other: Placebo Drug: NMD; 0.4mg sub-lingual nitroglycerin spray	N/A

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

74 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Apr 1, 2014

Anticipated Primary Completion Date :

Dec 1, 2023

Anticipated Study Completion Date :

Jan 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Antioxidant Cocktail 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 Flow-Mediated Dilation will be determined at baseline and 2 hours following acute antioxidant treatment Other Names: Vitamin C Vitamin E Alpha Lipoic Acid Other: Placebo Flow-Mediated Dilation will be determined at baseline and 2 hours following acute antioxidant treatment Drug: NMD; 0.4mg sub-lingual nitroglycerin spray Nitroglycerin mediated dilation will be measured immediately following an administered 0.4mg dose of nitroglycerin spray, sub-lingual. Other Names: Generic name: Nitrolingual Manufacturer: Arbor Pharmaceuticals
Other: Biopsy 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 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

Arm

Intervention/Treatment

Experimental: Antioxidant Cocktail

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

Flow-Mediated Dilation will be determined at baseline and 2 hours following acute antioxidant treatment

Other Names:

Vitamin C

Vitamin E

Alpha Lipoic Acid

Other: Placebo

Flow-Mediated Dilation will be determined at baseline and 2 hours following acute antioxidant treatment

Drug: NMD; 0.4mg sub-lingual nitroglycerin spray

Nitroglycerin mediated dilation will be measured immediately following an administered 0.4mg dose of nitroglycerin spray, sub-lingual.

Other Names:

Generic name: Nitrolingual

Manufacturer: Arbor Pharmaceuticals

Other: Biopsy

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

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

Outcome Measures

Primary Outcome Measures

Acute Change in Flow mediated dilation [Change from baseline (2 hours)]
Flow-Mediated Dilation will be determined at baseline and 2 hours following acute antioxidant treatment

Secondary Outcome Measures

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