Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study of Gamma Tocopherol-enriched Supplement on Lower Airway Responses to Inhaled Wood Smoke in Healthy Adults (SmokeyT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03444298
Recruitment Status : Recruiting
First Posted : February 23, 2018
Last Update Posted : April 5, 2019
Sponsor:
Collaborator:
National Institute of Environmental Health Sciences (NIEHS)
Information provided by (Responsible Party):
University of North Carolina, Chapel Hill

Brief Summary:
Purpose: To determine the efficacy of 1400 mg gamma tocopherol-enriched supplement for mitigating inhaled wood smoke particle-induced airway inflammation in healthy adults with no more than mild asthma.

Condition or disease Intervention/treatment Phase
Airway Inflammation Asthma Drug: Gamma Tocopherol Drug: Placebo Phase 2

Detailed Description:

Particulate matter (PM) is a leading cause of respiratory tract and cardiovascular disease in the United States and world-wide. Wood smoke particles (WSP) derived from wildland and other fires account for a significant fraction of ambient air PM. Health effects associated with WSP include acute bronchitis, asthma exacerbation, pneumonia, cough and systemic inflammation. While these effects are seen in both healthy and asthmatic individuals, many studies indicate that asthmatics have increased susceptibility to the effects of WSP. The investigators have developed a 500 μg/m3 WSP exposure protocol (levels similar to those encountered by firefighters and residents in close proximity to wildland burn sites) that induces airway and systemic inflammation in healthy volunteers. As with other pollutants, these inflammatory responses modulate non-specific bronchial reactivity (NSBR), inflammatory cell recruitment to the airways (primarily neutrophils), and potentially cardiovascular function.

The investigators have focused on gamma tocopherol (γT) as a nutritional intervention to prevent inflammatory responses to air pollutants such as WSP. Building on animal and in vitro preclinical studies, the investigators have established that 1400 mg/day of oral γT-enriched supplement for 7 and 14 days in healthy volunteers and mild asthmatics, respectively, inhibited neutrophil influx into the airways, reduced production of sputum mucins, and improved mucociliary clearance following challenge with inhaled endotoxin, another common component of PM. The findings occurred in the context of significantly increased plasma concentrations of γT and its active metabolite 2,7,8-trimethyl-2-(β-Carboxy-Ethyl)-6-Hydroxychroman (γ-CEHC). Given the findings in these early phase clinical trials, γT supplementation is an attractive approach to prevent WSP-induced adverse health effects. The investigators propose to use γT supplementation in a human model of WSP inhalation to mitigate key features of airway inflammation: inflammatory cell recruitment, production of inflammatory cytokines and mucous, and changes in airway physiology.

Gamma tocopherol will be administered in softgel form, with each softgel containing 700 mg of tocopherols, 89.5% of which is d-gamma tocopherol. Subjects will consume two softgels by mouth once daily for 7 days. This dosing regimen was chosen based on the results of the investigators' previous early phase clinical trials examining the impact of gamma tocopherol on lipopolysaccharide (LPS) -induced airway inflammation in healthy adults and adults with asthma. These studies tested a 7 and 14 day course of treatment, respectively, and found similar plasma concentrations of γT and active metabolites in both studies. Furthermore, the investigators showed in both studies that γT significantly reduced LPS-induced sputum neutrophilia compared to placebo. Based on the previous findings, the investigators will now study the efficacy of γT for mitigating WSP-induced airway inflammation.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 35 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: Subjects will be allocated to begin the first period of the crossover study with placebo or gamma tocopherol treatment using permuted block randomization with a block size of 4 (2 placebo, 2 gamma tocopherol for the first treatment period of the protocol).
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description:

The randomization schedule will be generated by the biostatistician and provided to the investigational pharmacy. Only the biostatistician and the pharmacist will have access to the randomization schedule.

Participants will consume 1400 mg of γT-enriched supplement or matching placebo once daily for 7 days.

Primary Purpose: Treatment
Official Title: A Phase II Randomized, Double Blinded, Placebo-controlled Study of Gamma Tocopherol-enriched Supplement on Lower Airway Responses to Inhaled Wood Smoke in Healthy Adults
Actual Study Start Date : June 8, 2018
Estimated Primary Completion Date : February 2021
Estimated Study Completion Date : March 2021


Arm Intervention/treatment
Placebo Comparator: Placebo first, then Gamma Tocopherol
Participants that are randomized to placebo treatment will take a short treatment course of Safflower Oil followed by chamber exposure with wood smoke particulate. After a 4-week washout period, participants will cross over to the gamma Tocopherol (active) treatment group.
Drug: Gamma Tocopherol
Each dose consists of two (700 mg) capsules by mouth once daily for a total of 7 days.
Other Name: Vitamin E

Drug: Placebo
Each dose consists of two (700 mg) capsules by mouth once daily for a total of 7 days.
Other Name: Safflower Oil

Active Comparator: GammaTocopherol first, then Placebo
Participants that are randomized γT treatment will take a short treatment course of gamma Tocopherol followed by chamber exposure with WSP. After a 4-week washout period, participants will cross over to the placebo treatment group.
Drug: Gamma Tocopherol
Each dose consists of two (700 mg) capsules by mouth once daily for a total of 7 days.
Other Name: Vitamin E

Drug: Placebo
Each dose consists of two (700 mg) capsules by mouth once daily for a total of 7 days.
Other Name: Safflower Oil




Primary Outcome Measures :
  1. change in sputum % neutrophils with WSP exposure [ Time Frame: baseline, and 4 hours post exposure ]
    A comparison of the WSP-induced change in sputum % neutrophils (Post-WSP sputum - Pre-WSP sputum) during gamma tocopherol treatment with the WSP-induced change in sputum % neutrophils during placebo treatment.


Secondary Outcome Measures :
  1. change in absolute neutrophil count (ANC) in peripheral blood with WSP exposure [ Time Frame: baseline, and 4 hours post exposure ]
    A comparison of the WSP-induced change in peripheral blood ANC (Post-WSP sputum - Pre-WSP sputum) during gamma tocopherol treatment with the WSP-induced change in peripheral blood ANC during placebo treatment.



Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Age 18-45 years, inclusive, of both genders
  2. Negative pregnancy test for females who are not s/p hysterectomy with oophorectomy
  3. Forced expiratory volume at one second (FEV1) of at least 75% of predicted (without use of bronchodilating medications for 12 hours), consistent with lung function of persons with no more than mild intermittent or mild persistent asthma.
  4. Oxygen saturation of <93% and blood pressure within the following limits: (Systolic between 150-85 mmHg, Diastolic between 90-50 mmHg).
  5. Ability to provide an induced sputum sample.
  6. Subject must demonstrate a ≥10% increase in sputum neutrophils following inhaled WSP exposure, when compared to baseline sputum (to be completed in a separate protocol).
  7. Ability/willingness to discontinue inhaled corticosteroids, montelukast, and cromolyn for 2 weeks without increased symptoms or increased need for beta agonist rescue medication prior to screening and through the course of the study.

Exclusion Criteria

Patients who meet any of these criteria are not eligible for enrollment as study participants:

  1. Clinical contraindications:

    1. Any chronic medical condition considered by the PI as a contraindication to the exposure study including significant cardiovascular disease, diabetes, chronic renal disease, chronic thyroid disease, history of chronic infections/immunodeficiency.
    2. Viral upper respiratory tract infection within 4 weeks of challenge.
    3. Any acute infection requiring antibiotics within 4 weeks of exposure or fever of unknown origin within 4 weeks of challenge.
    4. Abnormal physical findings at the baseline visit, including but not limited to abnormalities on auscultation, temperature of 37.8° C, Systolic BP > 150mm Hg or < 85 mm Hg; or Diastolic BP > 90 mm Hg or < 50 mm Hg, or pulse oximetry saturation reading less than 93%.
    5. Physician directed emergency treatment for an asthma exacerbation within the preceding 12 months.
    6. Moderate or severe asthma
    7. Exacerbation of asthma more than 2x/weeks which would be characteristic of a person with moderate or severe persistent asthma as outlined in the current National Asthma Education and Prevention Program (NAEPP) guidelines for diagnosis and management of asthma
    8. Daily requirement for albuterol due to asthma symptoms (cough, wheeze, chest tightness) which would be characteristic of a person with moderate or severe persistent asthma as outlined in the current NHLBI guidelines for diagnosis and management of asthma (not to include prophylactic use of albuterol prior to exercise).
    9. Nighttime symptoms of cough or wheeze greater than 1x/week at baseline (not during a clearly recognized viral induced asthma exacerbation) which would be characteristic of a person of moderate or severe persistent asthma as outlined in the current NHLBI guidelines for the diagnosis and management of asthma.
    10. History of intubation for asthma
    11. If there is a history of allergic rhinitis, subjects must be asymptomatic of allergic rhinitis at the time of study enrollment.
    12. Mental illness or history of drug or alcohol abuse that, in the opinion of the investigator, would interfere with the participant's ability to comply with study requirements.
    13. Cigarette smoking > 1 pack per month
    14. Unwillingness to use reliable contraception if sexually active (IUD, birth control pills/patch, condoms).
    15. Abnormal prothrombin time (PT) or activated partial thromboplastin time (aPTT) values at screening or during the treatment period. Normal values will be those published by the clinical lab (Labcorp, INC).
    16. Use of immunosuppressive or anticoagulant medications including routine use of NSAIDS. Oral contraceptives are acceptable, as are Antidepressants and other medications may be permitted if, in the opinion of the investigator, the medication will not interfere with the study procedures or compromise safety and if the dosage has been stable for 1 month.
    17. Orthopedic injuries or impediments that would preclude bicycle or treadmill exercise.
    18. Inability to avoid NSAIDS, Multivitamins, Vitamin C or E or herbal supplements.
    19. Allergy/sensitivity to study drugs or their formulations
    20. Known hypersensitivity to methacholine or to other parasympathomimetic agents
    21. Unwillingness to avoid coffee, tea, cola drinks, chocolate, or other foods containing caffeine after midnight on the days that methacholine challenge testing is to be performed.
  2. Pregnant/nursing women and children (< 18 years as this is age of majority in North Carolina) will also be excluded since the risks associated with woodsmoke exposure to the fetus or child, respectively, are unknown and cannot be justified for this non-therapeutic protocol. Individuals over 45 years of age will not be included due to the increased possibility of co-morbidities and need for prohibited medications.
  3. Inability or unwillingness of a participant to give written informed consent.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03444298


Contacts
Layout table for location contacts
Contact: Katie H Mills 919-843-6598 katherine_mills@med.unc.edu
Contact: Carole Robinette, MS 919-966-5638 carole_robinette@med.unc.edu

Locations
Layout table for location information
United States, North Carolina
UNC Center for Environmental Medicine, Asthma and Lung Biology Recruiting
Chapel Hill, North Carolina, United States, 27599
Contact: Katherine Mills    919-843-6598      
Sponsors and Collaborators
University of North Carolina, Chapel Hill
National Institute of Environmental Health Sciences (NIEHS)
Investigators
Layout table for investigator information
Principal Investigator: Allison J Burbank, MD Assistant Professor

Publications:
Layout table for additonal information
Responsible Party: University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier: NCT03444298     History of Changes
Other Study ID Numbers: 17-2303
5R01ES025124 ( U.S. NIH Grant/Contract )
First Posted: February 23, 2018    Key Record Dates
Last Update Posted: April 5, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Layout table for MeSH terms
Inflammation
Pathologic Processes
Tocopherols
Vitamin E
Tocotrienols
alpha-Tocopherol
gamma-Tocopherol
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Vitamins
Micronutrients
Nutrients
Growth Substances