Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Impact of Smoking Cessation and γ-Tocopherol to Restore Vascular Endothelial Function

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Richard Bruno, University of Connecticut
ClinicalTrials.gov Identifier:
NCT01314443
First received: March 10, 2011
Last updated: January 3, 2014
Last verified: January 2014

March 10, 2011
January 3, 2014
January 2011
November 2011   (final data collection date for primary outcome measure)
Absolute Change in Brachial Artery Flow-mediated Dilation at Day 7 From Day 0 [ Time Frame: Day 0 and 7 of intervention ] [ Designated as safety issue: No ]
Flow-mediated dilation (FMD) of the brachial artery is measured to assess vascular endothelial function. FMD is obtained by monitoring change in vessel diameter before and after brachial artery occlusion with a blood pressure cuff. The unit of FMD is % and is calculated using the following equation: FMD = [(peak dilation at post occlusion - vessel diameter at preocclusion)/vessel diameter at preocclusion]*100.
Change from baseline in brachial artery flow-mediated dilation at 1 day and 7 days [ Time Frame: 1 day and 7 days post-intervention ] [ Designated as safety issue: No ]
Flow-mediated dilation of the brachial artery, a measure of vascular endothelial function, will be assessed in a non-invasive manner using ultrasound technology.
Complete list of historical versions of study NCT01314443 on ClinicalTrials.gov Archive Site
  • Absolute Change From Baseline in Plasma Gamma-tocopherol (Vitamin E) at Day 7 From Day 0. [ Time Frame: Day 0 and 7 of intervention ] [ Designated as safety issue: No ]
    Plasma measurements of gamma-tocopherol was assessed in response to smoking cessation and in combination with gamma-tocopherol (vitamin E) supplementation.
  • Absolute Change From Baseline in Plasma Malondialdehyde at Day 7 From Day 0. [ Time Frame: Day 0 and 7 of intervention ] [ Designated as safety issue: No ]
    Plasma measurements of malondialdehyde, a marker of lipid peroxidation was assessed in response to smoking cessation and in combination with gamma-tocopherol (vitamin E) supplementation
Change from baseline in biomarkers of oxidative stress and antioxidant status at 1 day and 7 days. [ Time Frame: 1 day and 7 days post-intervention ] [ Designated as safety issue: No ]
Plasma measurements of oxidative stress biomarkers and antioxidant status will be assessed in response to smoking cessation and in combination with gamma-tocopherol (vitamin E) supplementation.
Not Provided
Not Provided
 
Impact of Smoking Cessation and γ-Tocopherol to Restore Vascular Endothelial Function
Cardioprotective Synergy of Smoking Cessation and γ-Tocopherol in Restoring Vascular Endothelial Function

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.

Not Provided
Interventional
Phase 1
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Endothelial Dysfunction
  • Other: Nicotine Replacement Therapy (NRT)
    Participants will quit smoking with nicotine patches
    Other Names:
    • Nicotine patches
    • NicoDerm
  • Dietary Supplement: Gamma-Tocopherol
    Participants will take gamma-tocopherol (500 mg/d) supplements for 7 days
    Other Name: Vitamin E
  • Other: Placebo
    Participants will take placebo for 7 days
    Other Name: Corn oil
  • Behavioral: Smoking cessation
    Participants will quit smoking without any pharmacological aids
  • Experimental: Placebo + Smoking Cessation
    Individuals will quit smoking without use of nicotine replacement therapy (NRT) and ingest a placebo for 7 days
    Interventions:
    • Other: Placebo
    • Behavioral: Smoking cessation
  • Experimental: Supplement + Smoking Cessation
    Individuals will quit smoking without the use of nicotine replacement therapy (NRT) and ingest a gamma-tocopherol supplement for 7 days
    Interventions:
    • Dietary Supplement: Gamma-Tocopherol
    • Behavioral: Smoking cessation
  • Experimental: Placebo + Nicotine Replacement Therapy
    Individuals will quit smoking with the use of nicotine replacement therapy (NRT) and ingest a placebo for 7 days
    Interventions:
    • Other: Nicotine Replacement Therapy (NRT)
    • Other: Placebo
    • Behavioral: Smoking cessation
  • Experimental: Supplement + Nicotine Replacement Therapy
    Individuals will quit smoking with the use of nicotine replacement therapy (NRT) and ingest a gamma-tocopherol supplement for 7 days
    Interventions:
    • Other: Nicotine Replacement Therapy (NRT)
    • Dietary Supplement: Gamma-Tocopherol
    • Behavioral: Smoking cessation
Mah E, Pei R, Guo Y, Ballard KD, Barker T, Rogers VE, Parker BA, Taylor AW, Traber MG, Volek JS, Bruno RS. γ-Tocopherol-rich supplementation additively improves vascular endothelial function during smoking cessation. Free Radic Biol Med. 2013 Dec;65:1291-9. doi: 10.1016/j.freeradbiomed.2013.09.016. Epub 2013 Sep 27.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
67
April 2014
November 2011   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • male or female between 18-60 y,
  • premenopausal status for women
  • healthy, verified by serum clinical chemistry
  • stable body weight (±5 lbs) for 2-mo and BMI 19-30 kg/m2
  • non-nutritional supplement user for >2-mo
  • free of known diseases including diabetes, CVD, cancer, infections, HIV/AIDS, hepatitis, and bleeding disorders
  • resting blood pressure <140/90 mm Hg;
  • smokers (≥10 cigarettes/d, ≥1 year)
  • maintaining normal exercise patterns (<7 h/week) and willingness to avoid exercise 24 h prior to blood sampling and vascular testing
  • willingness to ingest a dietary vitamin E supplement (gamma-tocopherol; 500 mg/d) or a placebo (composed of tocopherol-free corn oil) daily for 1 week.

Exclusion Criteria:

  • serum chemistry outside normal limits
  • alcohol consumption >3 drinks/d or >10 drinks per week
  • nutritional supplement user with past 2 months
  • >7 hours/week of exercise
  • use of any pharmacological therapy to treat high cholesterol or high blood pressure
  • pregnancy, lactation, or initiation or change in hormonal birth control within the previous 3 mo
  • use of vasoactive compounds (e.g. erectile dysfunction medication, omega 3-fatty acids, niacin)
  • suffering from major psychiatric illnesses
  • currently using non-nicotine aids or drugs to quit smoking; or 10) allergy to adhesive tape.
Both
18 Years to 60 Years
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01314443
H10-212
No
Richard Bruno, University of Connecticut
University of Connecticut
Not Provided
Principal Investigator: Richard S Bruno, PhD, RD University of Connecticut
University of Connecticut
January 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP