A Study of Gamma Tocopherol-enriched Supplement on Lower Airway Responses to Inhaled Wood Smoke in Healthy Adults
Condition: Airway Inflammation; Asthma
MeSH terms: Inflammation
Intervention: Gamma Tocopherol; Placebo
Intervention description: Each dose consists of two (700 mg) capsules by mouth once daily for a total of 7 days.; Each dose consists of two capsules by mouth once daily for a total of 7 days.
Intervention MeSH terms: Vitamin E; Tocopherols; Tocotrienols; alpha-Tocopherol; gamma-Tocopherol
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
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.
Enrollment: 16.0
Sex: All
Minimum age: 18 Years
Maximum age: 45 Years
Healthy volunteers: Accepts Healthy Volunteers

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.
    

Eligibility 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.