Airway Inflammation, Asthma
Conditions
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.
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. January 2022 update: The existing, custom source of gamma tocopherol expired during the protocol paused period during Covid. The Gamma t is replaced by Gamma E Gems, manufactured by Carlson Labs, each capsule with 577mg of gamma tocopherol, based on Certificate of Analysis. Subjects will continue to ingest 2 capsules at each dosing, for a total dose of 1154mg. The safflower oil placebo is replaced with a neutral oil capsule.
Interventions
DRUGGamma Tocopherol
Each dose consists of two (700 mg) capsules by mouth once daily for a total of 7 days.
DRUGPlacebo
Each dose consists of two capsules by mouth once daily for a total of 7 days.
Sponsors
National Institute of Environmental Health Sciences (NIEHS)
University of North Carolina, Chapel Hill
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, 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.
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).
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Sputum % Polymorphonuclear Neutrophils (PMN) With Wood Smoke Particulate (WSP) Exposure | baseline, and 4 hours post exposure | A comparison of the WSP-induced change in sputum % PMNs (Post-WSP sputum - Pre-WSP sputum) during gamma tocopherol treatment with the WSP-induced change in sputum % PMNs during placebo treatment. |
| Change in Sputum % PMNs With WSP Exposure | baseline, and 24 hours post exposure | A comparison of the WSP-induced change in sputum % PMNs (Post-WSP sputum - Pre-WSP sputum) during gamma tocopherol treatment with the WSP-induced change in sputum % PMNs during placebo treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Absolute PMN Count (ANC) in Sputum With WSP Exposure | baseline, and 4 hours post exposure | A comparison of the WSP-induced change in sputum ANC (Post-WSP sputum - Pre-WSP sputum) during gamma tocopherol treatment with the WSP-induced change in sputum ANC during placebo treatment. |
Countries
United States
Participant flow
Pre-assignment details
Eleven persons completed the study. The original gT dose was 1 dose every 12 hours x 4 (n=4 volunteers), but was ineffective in another study, so dosing was increased to 7 daily doses (n=4 volunteers). The gT expired during an 18 month pause for COVID-19 and could not be replaced, and a similarly potent commercially available gT-enriched preparation for 7 daily doses was then used for the final 3 persons. An intent-to-treat analysis of primary end points for all completed volunteers was used.
Participants by arm
| Arm | Count |
|---|---|
| Placebo First, Then Gamma Tocopherol Participants that are randomized to placebo treatment will take a short treatment course of Neutral 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.
Gamma Tocopherol: Each dose consists of two (700 mg) capsules by mouth once daily for a total of 7 days.
Placebo: Each dose consists of two capsules by mouth once daily for a total of 7 days. | 7 |
| 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.
Gamma Tocopherol: Each dose consists of two (700 mg) capsules by mouth once daily for a total of 7 days.
Placebo: Each dose consists of two capsules by mouth once daily for a total of 7 days. | 9 |
| Total | 16 |
Baseline characteristics
| Characteristic | Placebo First, Then Gamma Tocopherol | GammaTocopherol First, Then Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 00 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants | 9 Participants | 16 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 2 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 7 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 8 Participants | 11 Participants |
| Region of Enrollment United States | 7 Participants | 9 Participants | 16 Participants |
| Sex: Female, Male Female | 6 Participants | 5 Participants | 11 Participants |
| Sex: Female, Male Male | 1 Participants | 4 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 0 / 14 |
| other Total, other adverse events | 8 / 13 | 7 / 14 |
| serious Total, serious adverse events | 0 / 13 | 0 / 14 |
Outcome results
Primary
Change in Sputum % PMNs With WSP Exposure
A comparison of the WSP-induced change in sputum % PMNs (Post-WSP sputum - Pre-WSP sputum) during gamma tocopherol treatment with the WSP-induced change in sputum % PMNs during placebo treatment.
Time frame: baseline, and 24 hours post exposure
Population: Data are reported for participants who completed both arms and provided adequate sputum samples as outlined for each arm. Three participants did not have adequate sputum at 24 hours after active treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GammaTocopherol | Change in Sputum % PMNs With WSP Exposure | 39.87 percent PMNs | Standard Deviation 20.59 |
| Placebo | Change in Sputum % PMNs With WSP Exposure | 29.35 percent PMNs | Standard Deviation 28.3 |
p-value: 0.43Mixed Models Analysis
Primary
Change in Sputum % Polymorphonuclear Neutrophils (PMN) With Wood Smoke Particulate (WSP) Exposure
A comparison of the WSP-induced change in sputum % PMNs (Post-WSP sputum - Pre-WSP sputum) during gamma tocopherol treatment with the WSP-induced change in sputum % PMNs during placebo treatment.
Time frame: baseline, and 4 hours post exposure
Population: Data are reported for participants who completed both arms and provided adequate sputum samples.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GammaTocopherol | Change in Sputum % Polymorphonuclear Neutrophils (PMN) With Wood Smoke Particulate (WSP) Exposure | 18.00 percent PMNs | Standard Deviation 20.89 |
| Placebo | Change in Sputum % Polymorphonuclear Neutrophils (PMN) With Wood Smoke Particulate (WSP) Exposure | 14.75 percent PMNs | Standard Deviation 17.98 |
p-value: 0.67t-test, 2 sided
Secondary
Change in Absolute PMN Count (ANC) in Sputum With WSP Exposure
A comparison of the WSP-induced change in sputum ANC (Post-WSP sputum - Pre-WSP sputum) during gamma tocopherol treatment with the WSP-induced change in sputum ANC during placebo treatment.
Time frame: baseline, and 24 hours post exposure
Population: Data are reported for participants who completed both arms and provided adequate sputum samples as outlined for each arm. Three participants did not have adequate sputum at 24 hours after active treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GammaTocopherol | Change in Absolute PMN Count (ANC) in Sputum With WSP Exposure | 104.7 PMNs per mg sputum | Standard Deviation 146.5 |
| Placebo | Change in Absolute PMN Count (ANC) in Sputum With WSP Exposure | 96.7 PMNs per mg sputum | Standard Deviation 156.2 |
p-value: 0.92t-test, 2 sided
Secondary
Change in Absolute PMN Count (ANC) in Sputum With WSP Exposure
A comparison of the WSP-induced change in sputum ANC (Post-WSP sputum - Pre-WSP sputum) during gamma tocopherol treatment with the WSP-induced change in sputum ANC during placebo treatment.
Time frame: baseline, and 4 hours post exposure
Population: Data are reported for participants who completed both arms and provided adequate sputum samples as outlined for each arm. Three participants did not have adequate sputum at 24 hours after active treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GammaTocopherol | Change in Absolute PMN Count (ANC) in Sputum With WSP Exposure | 8.58 PMNs per mg sputum | Standard Deviation 150.6 |
| Placebo | Change in Absolute PMN Count (ANC) in Sputum With WSP Exposure | -20.51 PMNs per mg sputum | Standard Deviation 160.6 |
p-value: 0.27t-test, 2 sided
Post Hoc
2, 7,8-trimethyl-2S-(G-carboxyethyl)-6-hydroxychromane (g-CEHC) in Blood
The 2, 7,8-trimethyl-2S-(g-carboxyethyl)-6-hydroxychromane (g-CEHC) concentration will be determined in blood samples by high-performance liquid chromatography (HPLC).
Time frame: Baseline immediately before WSP challenge
Population: Data are reported for participants who completed both arms.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GammaTocopherol | 2, 7,8-trimethyl-2S-(G-carboxyethyl)-6-hydroxychromane (g-CEHC) in Blood | 1.912 microM | Standard Deviation 2.021 |
| Placebo | 2, 7,8-trimethyl-2S-(G-carboxyethyl)-6-hydroxychromane (g-CEHC) in Blood | 0.084 microM | Standard Deviation 0.08 |
p-value: <0.01t-test, 2 sided
Post Hoc
Alpha Tocopherol in Blood
The alpha tocopherol concentration will be determined in blood samples by high-performance liquid chromatography (HPLC).
Time frame: Baseline immediately before WSP challenge
Population: Data are reported for participants who completed both arms.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GammaTocopherol | Alpha Tocopherol in Blood | 22.54 microM | Standard Deviation 10.17 |
| Placebo | Alpha Tocopherol in Blood | 24.58 microM | Standard Deviation 3.4 |
p-value: 0.48t-test, 2 sided
Post Hoc
Eosinophils Per mg Sputum
A comparison of the WSP-induced sputum eosinophils after gamma tocopherol and placebo pre dosing values.
Time frame: up to 24 hours
Population: Data are reported for participants who completed both arms and provided adequate sputum samples.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GammaTocopherol | Eosinophils Per mg Sputum | 4 Hours | 0.17 Cells per mg (eosinophils) | Standard Deviation 0.33 |
| GammaTocopherol | Eosinophils Per mg Sputum | 24 Hours | 0.17 Cells per mg (eosinophils) | Standard Deviation 0.33 |
| Placebo | Eosinophils Per mg Sputum | 4 Hours | 0.20 Cells per mg (eosinophils) | Standard Deviation 0.52 |
| Placebo | Eosinophils Per mg Sputum | 24 Hours | 1.15 Cells per mg (eosinophils) | Standard Deviation 2.11 |
| Placebo | Eosinophils Per mg Sputum | 4 Hours | 7.10 Cells per mg (eosinophils) | Standard Deviation 12.33 |
| Placebo | Eosinophils Per mg Sputum | 24 Hours | 1.02 Cells per mg (eosinophils) | Standard Deviation 2.7 |
p-value: 0.98Mixed Models Analysis
p-value: 0.02Mixed Models Analysis
Post Hoc
GammaTocopherol in Blood
The gamma tocopherol concentration will be determined in blood samples by high-performance liquid chromatography (HPLC).
Time frame: Baseline immediately before WSP challenge
Population: Data are reported for participants who completed both arms.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GammaTocopherol | GammaTocopherol in Blood | 32.60 microM | Standard Deviation 7.45 |
| Placebo | GammaTocopherol in Blood | 4.64 microM | Standard Deviation 1.71 |
p-value: <0.0001t-test, 2 sided
Post Hoc
Interleukin-1 Beta (IL-1β) in Sputum
The IL-1β concentration will be determined in each sputum sample by immunoassay
Time frame: up to 24 hours
Population: Data are reported for participants who completed both arms and provided adequate sputum samples.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GammaTocopherol | Interleukin-1 Beta (IL-1β) in Sputum | 24 Hours | 798.3 pg/mL | Standard Deviation 497.1 |
| GammaTocopherol | Interleukin-1 Beta (IL-1β) in Sputum | 4 Hours | 798.3 pg/mL | Standard Deviation 497.1 |
| Placebo | Interleukin-1 Beta (IL-1β) in Sputum | 4 Hours | 674.2 pg/mL | Standard Deviation 494.9 |
| Placebo | Interleukin-1 Beta (IL-1β) in Sputum | 24 Hours | 469.6 pg/mL | Standard Deviation 237.4 |
| Placebo | Interleukin-1 Beta (IL-1β) in Sputum | 4 Hours | 654.4 pg/mL | Standard Deviation 438.3 |
| Placebo | Interleukin-1 Beta (IL-1β) in Sputum | 24 Hours | 675.2 pg/mL | Standard Deviation 630.6 |
p-value: 0.84Mixed Models Analysis
Post Hoc
Interleukin-6 (IL-6) in Sputum
The IL-6 concentration will be determined in each sputum sample by immunoassay
Time frame: up to 24 hours
Population: Data are reported for participants who completed both arms and provided adequate sputum samples.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GammaTocopherol | Interleukin-6 (IL-6) in Sputum | 4 Hours | 458.0 pg/mL | Standard Deviation 492.3 |
| GammaTocopherol | Interleukin-6 (IL-6) in Sputum | 24 Hours | 458.0 pg/mL | Standard Deviation 492.3 |
| Placebo | Interleukin-6 (IL-6) in Sputum | 4 Hours | 384.8 pg/mL | Standard Deviation 440.2 |
| Placebo | Interleukin-6 (IL-6) in Sputum | 24 Hours | 207.0 pg/mL | Standard Deviation 171.6 |
| Placebo | Interleukin-6 (IL-6) in Sputum | 4 Hours | 277.5 pg/mL | Standard Deviation 255.5 |
| Placebo | Interleukin-6 (IL-6) in Sputum | 24 Hours | 281.3 pg/mL | Standard Deviation 338 |
p-value: 0.59Mixed Models Analysis
Post Hoc
Interleukin-8 (IL-8) in Sputum
The IL-8 concentration will be determined in each sputum sample by immunoassay
Time frame: up to 24 hours
Population: Data are reported for participants who completed both arms and provided adequate sputum samples.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GammaTocopherol | Interleukin-8 (IL-8) in Sputum | 4 Hours | 30850 pg/mL | Standard Deviation 28306 |
| GammaTocopherol | Interleukin-8 (IL-8) in Sputum | 24 Hours | 30850 pg/mL | Standard Deviation 28306 |
| Placebo | Interleukin-8 (IL-8) in Sputum | 4 Hours | 31724 pg/mL | Standard Deviation 37505 |
| Placebo | Interleukin-8 (IL-8) in Sputum | 24 Hours | 17180 pg/mL | Standard Deviation 13083 |
| Placebo | Interleukin-8 (IL-8) in Sputum | 4 Hours | 25432 pg/mL | Standard Deviation 23198 |
| Placebo | Interleukin-8 (IL-8) in Sputum | 24 Hours | 36739 pg/mL | Standard Deviation 60134 |
p-value: 0.83Mixed Models Analysis
Post Hoc
Percent Eosinophils in Sputum
A comparison of the WSP-induced sputum % eosinophils versus predosing values with gamma tocopherol and placebo treatment.
Time frame: up to 24 hours
Population: Data are reported for participants who completed both arms and provided adequate sputum samples.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GammaTocopherol | Percent Eosinophils in Sputum | 24 Hours | 0.07 percent eosinophils | Standard Deviation 0.04 |
| GammaTocopherol | Percent Eosinophils in Sputum | 4 Hours | 0.07 percent eosinophils | Standard Deviation 0.04 |
| Placebo | Percent Eosinophils in Sputum | 24 Hours | 0.26 percent eosinophils | Standard Deviation 0.15 |
| Placebo | Percent Eosinophils in Sputum | 4 Hours | 0.04 percent eosinophils | Standard Deviation 0.08 |
| Placebo | Percent Eosinophils in Sputum | 4 Hours | 2.3 percent eosinophils | Standard Deviation 1.6 |
| Placebo | Percent Eosinophils in Sputum | 24 Hours | 0.39 percent eosinophils | Standard Deviation 0.33 |
p-value: 0.99Mixed Models Analysis
p-value: 0.04Mixed Models Analysis
Post Hoc
Tumor Necrosis Factor-alpha (TNF-a)
The TNF-a concentration will be determined in each sputum sample by immunoassay
Time frame: up to 24 hours
Population: Data are reported for participants who completed both arms and provided adequate sputum samples.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GammaTocopherol | Tumor Necrosis Factor-alpha (TNF-a) | 4 Hours | 35.67 pg/mL | Standard Deviation 25.88 |
| GammaTocopherol | Tumor Necrosis Factor-alpha (TNF-a) | 24 Hours | 35.67 pg/mL | Standard Deviation 25.88 |
| Placebo | Tumor Necrosis Factor-alpha (TNF-a) | 4 Hours | 127.7 pg/mL | Standard Deviation 342.7 |
| Placebo | Tumor Necrosis Factor-alpha (TNF-a) | 24 Hours | 13.77 pg/mL | Standard Deviation 12.63 |
| Placebo | Tumor Necrosis Factor-alpha (TNF-a) | 4 Hours | 25.18 pg/mL | Standard Deviation 20.84 |
| Placebo | Tumor Necrosis Factor-alpha (TNF-a) | 24 Hours | 29.23 pg/mL | Standard Deviation 26.18 |
p-value: 0.51Mixed Models Analysis