Endothelial Dysfunction clinical trials at UCLA

Electronic nicotine delivery systems (ENDS) are a new rapidly growing global epidemic. More recently, electronic (e-) hookahs, have increased in popularity in the United States, with the greatest uptake by young female adults, who endorse marketing claims that these products are safer alternatives to traditional flavored hookah tobacco smoking. Unlike other ENDS such as e-cigarettes, e-hookah bowls are used through traditional water-pipes, allowing the vapor-containing nicotine, propylene glycol, glycerin, and flavorings-to pass through a water-filled basin, potentially altering the vapor, before it is inhaled through the user's mouth. Contributing to e-hookah bowls' popularity is the belief that the flavored smoke is detoxified as it passes through the water-filled basin, rendering e-hookah a safer tobacco alternative. However, an e-hookah bowl delivers flavored nicotine by creating a vapor of fine particles and volatile organic compounds that could induce vascular toxicity. The objective of this project is to investigate the effects of e-hookah bowl inhalation on endothelial function, vascular biomarkers and volatile compounds; and molecular mechanisms underlying e-hookah induced endothelial injury using freshly harvested human endothelial cells with a specific role of nicotine. In a cross-over study design, the investigators will first assess endothelial function measured by brachial artery flow-mediated dilation and markers of oxidative stress and inflammation in 18 young healthy hookah smokers 21-39 years old, before and after two separate 30-minute e-hookah bowl inhalation sessions using one brand of nicotine-containing and nicotine-free e-hookah liquid and, for control comparison, before and after sham hookah smoking. Then, in freshly harvested venous endothelial cells the investigators will assess nitric oxide bioavailability, and expression of markers of inflammation and oxidative stress before and after the sessions. To compare specific exposures across conditions, the research team will measure changes in plasma nicotine, and highly specific urinary mercapturic acid metabolites of acrolein and benzene. This proposed study will provide critical scientific data on the impact of e-hookah inhalation on vascular health and mechanisms of exposure on known cardiac risk factors. Results will provide critical data to the FDA to inform the development of regulations specific to hookah.

In a young and healthy person, the production of nitric oxide (NO) by the endothelium, the inner lining of the blood vessel, is responsible for a) the ability of the blood vessel to dilate so it can increase its blood flow and b) act as an anti-clotting product to prevent blood clotting in those vessels. Under physiological stress either due to the development of a disease such as diabetes or simply from aging, the endothelial cells can be impacted and become dysfunctional thereby impairing their ability to make NO and even promote the development of blood clots. When such endothelial dysfunction occurs, it may be a precursor for the future development of cardiovascular (CV) disease like hypertension or even coronary artery disease later on in life in these patients. Therefore, the ability to somehow enhance the local production or availability of NO within such affected blood vessels in patients identified as prone to endothelial dysfunction could play a positive role in either preventing or delaying the onset of endothelial dysfunction and subsequent CV disease in such patients. COMP-4 is a safe, clinically available, well tolerated oral supplement that has been shown in the lab to increase NO production in a number of differing tissues including human vascular endothelial cells. In this proposed human study, the investigators plan on recruiting healthy, young participants willing to take COMP-4 for a 14 day period in whom the investigators will measure in a non-invasive way - by the use of ultrasound - the effect of COMP-4 on its ability to improve blood flow in one of the major blood vessels of the upper arm. In addition, the investigators will also determine whether COMP-4 will be capable of lowering in the blood the levels of two of the most studied inflammatory markers associated with endothelial dysfunction, IL-8 and PAI-1.