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

• Status: Suspended
• Trial end date: 2022-03-31
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: University of North Carolina, Chapel Hill
• Collaborator: National Institute of Environmental Health Sciences (NIEHS)
• Treatments: alpha-Tocopherol; gamma-Tocopherol; Tocopherols; Tocotrienols; Vitamin E

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.