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
  Purpose

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.


Condition Intervention Phase
Endothelial Dysfunction
Other: Nicotine Replacement Therapy (NRT)
Dietary Supplement: Gamma-Tocopherol
Other: Placebo
Behavioral: Smoking cessation
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Cardioprotective Synergy of Smoking Cessation and γ-Tocopherol in Restoring Vascular Endothelial Function

Resource links provided by NLM:


Further study details as provided by University of Connecticut:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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


Enrollment: 67
Study Start Date: January 2011
Estimated Study Completion Date: April 2014
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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
Dietary Supplement: Gamma-Tocopherol
Participants will take gamma-tocopherol (500 mg/d) supplements for 7 days
Other Name: Vitamin E
Behavioral: Smoking cessation
Participants will quit smoking without any pharmacological aids
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: Nicotine Replacement Therapy (NRT)
Participants will quit smoking with nicotine patches
Other Names:
  • Nicotine patches
  • NicoDerm
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: 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
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
Behavioral: Smoking cessation
Participants will quit smoking without any pharmacological aids

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01314443

Locations
United States, Connecticut
University of Connecticut
Storrs, Connecticut, United States, 06269
Sponsors and Collaborators
University of Connecticut
Investigators
Principal Investigator: Richard S Bruno, PhD, RD University of Connecticut
  More Information

Publications:
Responsible Party: Richard Bruno, Associate Professor, University of Connecticut
ClinicalTrials.gov Identifier: NCT01314443     History of Changes
Other Study ID Numbers: H10-212
Study First Received: March 10, 2011
Results First Received: December 12, 2012
Last Updated: January 3, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Connecticut:
smoking cessation
gamma-tocopherol
nicotine-replacement therapy
oxidative stress

Additional relevant MeSH terms:
Nicotine
Gamma-Tocopherol
Tocopherols
Vitamin E
Alpha-Tocopherol
Tocotrienols
Ganglionic Stimulants
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Nicotinic Agonists
Cholinergic Agonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Antioxidants
Protective Agents
Vitamins
Micronutrients
Growth Substances

ClinicalTrials.gov processed this record on September 30, 2014