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
1 other identifier
interventional
67
1 country
1
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Jan 2011
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
January 1, 2011
CompletedFirst Submitted
Initial submission to the registry
March 10, 2011
CompletedFirst Posted
Study publicly available on registry
March 14, 2011
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 1, 2011
CompletedResults Posted
Study results publicly available
March 6, 2013
CompletedStudy Completion
Last participant's last visit for all outcomes
December 1, 2014
CompletedJanuary 21, 2015
January 1, 2015
10 months
March 10, 2011
December 12, 2012
January 19, 2015
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Absolute Change in Brachial Artery Flow-mediated Dilation at Day 7 From Day 0
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.
Day 0 and 7 of intervention
Secondary Outcomes (2)
Absolute Change From Baseline in Plasma Gamma-tocopherol (Vitamin E) at Day 7 From Day 0.
Day 0 and 7 of intervention
Absolute Change From Baseline in Plasma Malondialdehyde at Day 7 From Day 0.
Day 0 and 7 of intervention
Study Arms (4)
Placebo + Smoking Cessation
EXPERIMENTALIndividuals will quit smoking without use of nicotine replacement therapy (NRT) and ingest a placebo for 7 days
Supplement + Smoking Cessation
EXPERIMENTALIndividuals will quit smoking without the use of nicotine replacement therapy (NRT) and ingest a gamma-tocopherol supplement for 7 days
Placebo + Nicotine Replacement Therapy
EXPERIMENTALIndividuals will quit smoking with the use of nicotine replacement therapy (NRT) and ingest a placebo for 7 days
Supplement+Nicotine Replacement Therapy
EXPERIMENTALIndividuals will quit smoking with the use of nicotine replacement therapy (NRT) and ingest a gamma-tocopherol supplement for 7 days
Interventions
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
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
University of Connecticut
Storrs, Connecticut, 06269, United States
Related Publications (2)
Mah E, Pei R, Guo Y, Ballard KD, Barker T, Rogers VE, Parker BA, Taylor AW, Traber MG, Volek JS, Bruno RS. gamma-Tocopherol-rich supplementation additively improves vascular endothelial function during smoking cessation. Free Radic Biol Med. 2013 Dec;65:1291-1299. doi: 10.1016/j.freeradbiomed.2013.09.016. Epub 2013 Sep 27.
PMID: 24075893RESULTMah E, Pei R, Guo Y, Masterjohn C, Ballard KD, Taylor BA, Taylor AW, Traber MG, Volek JS, Bruno RS. Greater gamma-tocopherol status during acute smoking abstinence with nicotine replacement therapy improved vascular endothelial function by decreasing 8-iso-15(S)-prostaglandin F2alpha. Exp Biol Med (Maywood). 2015 Apr;240(4):527-33. doi: 10.1177/1535370214556948. Epub 2014 Oct 30.
PMID: 25361769DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
Very few women were enrolled thereby precluding any assessment of potential gender differences for our outcome variables.
Results Point of Contact
- Title
- Richard Bruno, PhD, RD
- Organization
- Ohio State University
Study Officials
- PRINCIPAL INVESTIGATOR
Richard S Bruno, PhD, RD
University of Connecticut
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- BASIC SCIENCE
- Intervention Model
- FACTORIAL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Associate Professor
Study Record Dates
First Submitted
March 10, 2011
First Posted
March 14, 2011
Study Start
January 1, 2011
Primary Completion
November 1, 2011
Study Completion
December 1, 2014
Last Updated
January 21, 2015
Results First Posted
March 6, 2013
Record last verified: 2015-01