Endothelial DysfunctionPhase 1/2NCT01314443
Impact of Smoking Cessation and γ-Tocopherol to Restore Vascular Endothelial Function
A Phase 1/2 study testing Nicotine Replacement Therapy (NRT), Gamma-Tocopherol and Smoking cessation in people with Endothelial Dysfunction, run by University of Connecticut at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Endothelial Dysfunction
- What is being tested?
- Nicotine Replacement Therapy (NRT), Gamma-Tocopherol and Smoking cessation
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 67 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2011to Dec 2014
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Connecticut
Storrs, Connecticut, 06269
About this study
Official title: 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.
Read the 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
- Being tested
- Nicotine Replacement Therapy (NRT), Gamma-Tocopherol, Placebo, Smoking cessation
- Keywords
- smoking cessation, gamma-tocopherol, nicotine-replacement therapy, oxidative stress
- Medical subject headings
- Smoking Cessation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nicotine Replacement Therapy (NRT)Other
Also called Nicotine patches, NicoDerm
Participants will quit smoking with nicotine patches
Gamma-TocopherolDietary supplement
Also called Vitamin E
Participants will take gamma-tocopherol (500 mg/d) supplements for 7 days
PlaceboOther
Also called Corn oil
Participants will take placebo for 7 days
Smoking cessationBehavioural
Participants will quit smoking without any pharmacological aids
| Study group | Role | What they receive |
|---|---|---|
| Placebo + Smoking Cessation | Experimental | Individuals will quit smoking without use of nicotine replacement therapy (NRT) and ingest a placebo for 7 days Receives: Other: Placebo; Behavioral: Smoking cessation |
| Supplement + Smoking Cessation | Experimental | Individuals will quit smoking without the use of nicotine replacement therapy (NRT) and ingest a gamma-tocopherol supplement for 7 days Receives: Dietary Supplement: Gamma-Tocopherol; Behavioral: Smoking cessation |
| Placebo + Nicotine Replacement Therapy | Experimental | Individuals will quit smoking with the use of nicotine replacement therapy (NRT) and ingest a placebo for 7 days Receives: Other: Nicotine Replacement Therapy (NRT); Other: Placebo |
| Supplement+Nicotine Replacement Therapy | Experimental | Individuals will quit smoking with the use of nicotine replacement therapy (NRT) and ingest a gamma-tocopherol supplement for 7 days Receives: Other: Nicotine Replacement Therapy (NRT); Dietary Supplement: Gamma-Tocopherol |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Plasma measurements of gamma-tocopherol was assessed in response to smoking cessation and in combination with gamma-tocopherol (vitamin E) supplementation.
Measured: Day 0 and 7 of intervention
Absolute Change From Baseline in Plasma Malondialdehyde at Day 7 From Day 0.
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
Measured: Day 0 and 7 of intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Mar 2011 (estimated)
- Study startJan 2011
- Primary completionNov 2011
- Study completionDec 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Endothelial DysfunctionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 67 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Connecticut
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Richard Bruno, University of Connecticut
- Investigators
- Richard S Bruno, PhD, RD, Principal investigator, University of Connecticut
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01314443
- Sponsor's protocol ID
- H10-212
- Status last verified
- Jan 2015
- First submitted
- 10 Mar 2011
- Last updated
- 21 Jan 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 24075893Mah 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.
PubMed 25361769
Study at a glance
From the registry record, last updated by the sponsor on 21 Jan 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cardioprotective Synergy of Smoking Cessation and γ-Tocopherol in Restoring Vascular Endothelial Function
- ClinicalTrials.gov ID
- NCT01314443
- Acronym / sponsor ID
- H10-212
- Conditions
- Endothelial Dysfunction
- Keywords
- smoking cessation, gamma-tocopherol, nicotine-replacement therapy, oxidative stress
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 67 participants (actual)
- Lead sponsor
- University of ConnecticutUniversity, hospital or other
- Study start
- Jan 2011
- Primary completion
- Nov 2011 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 14 Mar 2011 (estimated)
- Results
- Posted 6 Mar 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Placebo + Smoking Cessation | Experimental | Other: Placebo, Behavioral: Smoking cessationIndividuals will quit smoking without use of nicotine replacement therapy (NRT) and ingest a placebo for 7 days |
| Supplement + Smoking Cessation | Experimental | Dietary Supplement: Gamma-Tocopherol, Behavioral: Smoking cessationIndividuals will quit smoking without the use of nicotine replacement therapy (NRT) and ingest a gamma-tocopherol supplement for 7 days |
| Placebo + Nicotine Replacement Therapy | Experimental | Other: Nicotine Replacement Therapy (NRT), Other: PlaceboIndividuals will quit smoking with the use of nicotine replacement therapy (NRT) and ingest a placebo for 7 days |
| Supplement+Nicotine Replacement Therapy | Experimental | Other: Nicotine Replacement Therapy (NRT), Dietary Supplement: Gamma-TocopherolIndividuals will quit smoking with the use of nicotine replacement therapy (NRT) and ingest a gamma-tocopherol supplement for 7 days |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Nicotine Replacement Therapy (NRT)Also: Nicotine patches, NicoDermParticipants will quit smoking with nicotine patches | Other | Placebo + Nicotine Replacement Therapy, Supplement+Nicotine Replacement Therapy |
| Gamma-TocopherolAlso: Vitamin EParticipants will take gamma-tocopherol (500 mg/d) supplements for 7 days | Dietary supplement | Supplement + Smoking Cessation, Supplement+Nicotine Replacement Therapy |
| PlaceboAlso: Corn oilParticipants will take placebo for 7 days | Other | Placebo + Nicotine Replacement Therapy, Placebo + Smoking Cessation |
| Smoking cessationParticipants will quit smoking without any pharmacological aids | Behavioural | Placebo + Smoking Cessation, Supplement + Smoking Cessation |
Primary outcome
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.
2 secondary outcomes
Absolute Change From Baseline in Plasma Gamma-tocopherol (Vitamin E) at Day 7 From Day 0.
Time frame: 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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jan 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 24075893Mah 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.
- Derived from this study: PubMed 25361769Mah 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Richard S Bruno, PhD, RD principal investigator
University of Connecticut
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Nicotine Replacement Therapy (NRT), Gamma-Tocopherol and Smoking cessation in people with Endothelial Dysfunction, run by University of Connecticut at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Jan 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Mar 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Absolute Change in Brachial Artery Flow-mediated Dilation at Day 7 From Day 0 (time frame: Day 0 and 7 of intervention). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01314443, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jan 2015.