Impact of Smoking Cessation and γ-Tocopherol to Restore Vascular Endothelial Function
Condition: Endothelial Dysfunction
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      Cigarette smoking is a significant risk factor for cardiovascular disease (CVD) and is the
      leading cause of premature mortality in the US. The detrimental effects of smoking on
      vascular dysfunction are attributed to the effects of smoke itself and the inflammatory
      responses it induces. Smoking cessation restores vascular function by alleviating these
      stress responses. However, smoking cessation with nicotine replacement therapy (NRT), the
      prevailing approach to mitigate tobacco dependence, fails to allow full restoration of
      vascular function. Thus, a critical public health problem exists to understand how NRT
      prevents restoration of vascular function and how these NRT-mediated impairments can be
      overcome by using gamma-tocopherol (g-T) as an innovative co-therapy. The objective of this
      study is to conduct a clinical intervention trial that aims to reduce CVD risk by defining
      how smoking cessation and g-T restore vascular function. The hypothesis is that smoking
      cessation and dietary g-T supplementation will synergistically restore smoking-induced
      impairments in vascular function by ameliorating oxidative/nitrosative stress responses, and
      that g-T will facilitate full restoration of vascular function otherwise precluded by NRT. A
      placebo-controlled, g-T intervention study will be conducted in cigarette smokers undergoing
      nicotine-free or NRT smoking cessation. Prior to and after 24 h and 7 days of placebo or g-T
      administration, vascular function will be evaluated using a non-invasive ultrasound technique
      and an array of antioxidants and biomarkers for vascular inflammation and
      oxidative/nitrosative stress responses will be assessed. Collectively, these studies will
      help identify how vascular function is regulated in individuals undergoing smoking cessation,
      and whether g-T can be used as a strategy to better improve vascular function during smoking
      cessation.
    

Detailed description: 
      While it is well known that smoking cessation reduces the risk of cardiovascular disease
      (CVD), the rate in which CVD risk is normalized is relatively slow. This suggests a need to
      better define co-therapies that target oxidative stress and inflammatory responses that
      otherwise impair vascular function. In this randomized placebo-controlled clinical study,
      smokers undergoing smoking cessation with or without nicotine replacement therapy will
      receive dietary supplementation of gamma-tocopherol (500 mg/day) or placebo for 7 days. Their
      vascular function and biomarkers of CVD risk (inflammatory proteins, antioxidants, oxidized
      lipids) will be assessed prior to, and at 1 day and 7 days during smoking cessation with and
      without gamma-tocopherol supplementation to define potential mechanisms by which
      gamma-tocopherol may accelerate the restoration of vascular function and assist in reducing
      CVD risk.
    

Intervention name(s): Nicotine Replacement Therapy (NRT); Gamma-Tocopherol; Placebo; Smoking cessation
Intervention type(s): Other; Dietary Supplement; Other; Behavioral
Intervention description(s): Participants will quit smoking with nicotine patches; Participants will take gamma-tocopherol (500 mg/d) supplements for 7 days; Participants will take placebo for 7 days; Participants will quit smoking without any pharmacological aids
Other intervention name(s): Nicotine patches; NicoDerm; Vitamin E; Corn oil
Intervention MeSH terms: Vitamin E; Tocopherols; Tocotrienols; alpha-Tocopherol; gamma-Tocopherol; Nicotine
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: smoking cessation; gamma-tocopherol; nicotine-replacement therapy; oxidative stress