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

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
67

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Connecticut

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • 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

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2011

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 1, 2011

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2014

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 10, 2011

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 11, 2011

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 14, 2011

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 21, 2015

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 19, 2015

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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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