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

NCT ID: NCT01314443

Last Updated: 2015-01-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 67 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-01-31
• Study Completion Date: 2014-12-31

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.

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.

Conditions

Endothelial Dysfunction

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: TRIPLE

Study Groups

Placebo + Smoking Cessation

Individuals will quit smoking without use of nicotine replacement therapy (NRT) and ingest a placebo for 7 days

Group Type: EXPERIMENTAL

Placebo

Intervention Type: OTHER

Participants will take placebo for 7 days

Smoking cessation

Intervention Type: BEHAVIORAL

Participants will quit smoking without any pharmacological aids

Supplement + Smoking Cessation

Individuals will quit smoking without the use of nicotine replacement therapy (NRT) and ingest a gamma-tocopherol supplement for 7 days

Group Type: EXPERIMENTAL

Gamma-Tocopherol

Intervention Type: DIETARY_SUPPLEMENT

Participants will take gamma-tocopherol (500 mg/d) supplements for 7 days

Smoking cessation

Intervention Type: BEHAVIORAL

Participants will quit smoking without any pharmacological aids

Placebo + Nicotine Replacement Therapy

Individuals will quit smoking with the use of nicotine replacement therapy (NRT) and ingest a placebo for 7 days

Group Type: EXPERIMENTAL

Nicotine Replacement Therapy (NRT)

Intervention Type: OTHER

Participants will quit smoking with nicotine patches

Placebo

Intervention Type: OTHER

Participants will take placebo for 7 days

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

Group Type: EXPERIMENTAL

Nicotine Replacement Therapy (NRT)

Intervention Type: OTHER

Participants will quit smoking with nicotine patches

Gamma-Tocopherol

Intervention Type: DIETARY_SUPPLEMENT

Participants will take gamma-tocopherol (500 mg/d) supplements for 7 days

Interventions

Nicotine Replacement Therapy (NRT)

Participants will quit smoking with nicotine patches

Intervention Type: OTHER

Gamma-Tocopherol

Participants will take gamma-tocopherol (500 mg/d) supplements for 7 days

Intervention Type: DIETARY_SUPPLEMENT

Placebo

Participants will take placebo for 7 days

Intervention Type: OTHER

Smoking cessation

Participants will quit smoking without any pharmacological aids

Intervention Type: BEHAVIORAL

Other Intervention Names

Nicotine patches; NicoDerm; Vitamin E; Corn oil

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Connecticut

OTHER

Sponsor Role: lead

Responsible Party

Richard Bruno

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Richard S Bruno, PhD, RD

Role: PRINCIPAL_INVESTIGATOR

University of Connecticut

Locations

University of Connecticut

Storrs, Connecticut, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 24075893 (View on PubMed)

Mah 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.

Reference Type: DERIVED

PMID: 25361769 (View on PubMed)

Other Identifiers

H10-212

Identifier Type: -

Identifier Source: org_study_id