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

January 19, 2015 updated by: Richard Bruno, University of Connecticut

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

67

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Connecticut
      • Storrs, Connecticut, United States, 06269
        • University of Connecticut

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 60 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Factorial Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Placebo + Smoking Cessation
Individuals will quit smoking without use of nicotine replacement therapy (NRT) and ingest a placebo for 7 days
Other: Placebo
Participants will take placebo for 7 days
Other Names:
  • Corn oil
Behavioral: Smoking cessation
Participants will quit smoking without any pharmacological aids
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
Behavioral: Smoking cessation
Participants will quit smoking without any pharmacological aids
Dietary supplement: Gamma-Tocopherol
Participants will take gamma-tocopherol (500 mg/d) supplements for 7 days
Other Names:
  • Vitamin E
Experimental: Placebo + Nicotine Replacement Therapy
Individuals will quit smoking with the use of nicotine replacement therapy (NRT) and ingest a placebo for 7 days
Other: Placebo
Participants will take placebo for 7 days
Other Names:
  • Corn oil
Other: Nicotine Replacement Therapy (NRT)
Participants will quit smoking with nicotine patches
Other Names:
  • NicoDerm
  • Nicotine patches
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
Dietary supplement: Gamma-Tocopherol
Participants will take gamma-tocopherol (500 mg/d) supplements for 7 days
Other Names:
  • Vitamin E
Other: Nicotine Replacement Therapy (NRT)
Participants will quit smoking with nicotine patches
Other Names:
  • NicoDerm
  • Nicotine patches

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Absolute Change in Brachial Artery Flow-mediated Dilation at Day 7 From Day 0
Time Frame: Day 0 and 7 of intervention
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Absolute Change From Baseline in Plasma Gamma-tocopherol (Vitamin E) at Day 7 From Day 0.
Time Frame: Day 0 and 7 of intervention
Plasma measurements of gamma-tocopherol was assessed in response to smoking cessation and in combination with gamma-tocopherol (vitamin E) supplementation.
Day 0 and 7 of intervention
Absolute Change From Baseline in Plasma Malondialdehyde at Day 7 From Day 0.
Time Frame: Day 0 and 7 of intervention
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
Day 0 and 7 of intervention

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Connecticut

Investigators

  • Principal Investigator: Richard S Bruno, PhD, RD, University of Connecticut

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2011

Primary Completion (Actual)

November 1, 2011

Study Completion (Actual)

December 1, 2014

Study Registration Dates

First Submitted

March 10, 2011

First Submitted That Met QC Criteria

March 11, 2011

First Posted (Estimate)

March 14, 2011

Study Record Updates

Last Update Posted (Estimate)

January 21, 2015

Last Update Submitted That Met QC Criteria

January 19, 2015

Last Verified

January 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • H10-212

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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