Asthma
Conditions
Keywords
Asthma, Soy isoflavones, Eosinophils, Exhaled nitric oxide
Brief summary
An epidemiologic study of patients with asthma has shown that increased intake of soy isoflavones correlates with less severe asthma. In experimental animals, treatment with the soy isoflavone genistein reduces airways inflammation and hyper-responsiveness. In vitro studies performed by us have shows that genistein reduces release of inflammatory compounds by human blood eosinophils. The purpose of this pilot study is to determine whether dietary supplementation with soy isoflavones has effects in patients with asthma. 20 patients with asthma will supplement their diet with a soy isoflavone capsule for 4 weeks. Before and after the supplementation period, we will measure lung function, exhaled nitric oxide (a marker for airway inflammation), collect exhaled breath condensate to measure levels of inflammatory mediators in the airways, and isolate peripheral blood eosinophils to assess the impact of soy isoflavones on their function. We hypothesize that dietary supplementation with soy isoflavones will reduce exhaled nitric oxide level, reduce the inflammatory mediators in the exhaled breath condensate, and reduce the ability of eosinophils to release inflammatory molecules. Identifying if these hypothesized effects of soy isoflavones exist in asthma will provide a justification for further clinical studies.
Detailed description
This is a prospective pilot study to be conducted in 20 subjects with asthma. The participant will undergo the following procedures: 1. Completion of a questionnaire that asks for information about asthma including symptoms, medications, and ability to participate in activities. 2. Measurement of exhaled nitric oxide (NO) in which subjects will breathe slowly into a tube. This test takes about 5 minutes. 3. Collection of the air exhaled from the lungs and condensing it into a liquid form. This is called an exhaled breath condensate. This procedure involves breathing slowing into a tube for a period of 15 minutes. The measurements determined by this method are exclusively for research purposes and not used in routine clinical settings. 4. Measurement of lung function with a spirometer. This involves breathing in and out forcefully through a mouthpiece. 5. Collection of 60 ml (4 tablespoons) of blood to measure genistein (the major component of the soy isoflavone) levels and eosinophil function. These measurements are also for research purposes and not routinely used clinically. Each of the above measurements will be made before and after the 4 week period of dietary supplementation with soy isoflavones.
Interventions
DRUGSoy isoflavones
Sponsors
Northwestern University
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
* Ages 18-50, males and females * Physician diagnosis of asthma; requires daily asthma medication * Moderate persistent disease (NAEPP guidelines) * FEV1 65 to 90% of predicted * At least 12% increase in FEV1 15-30 minutes after inhaling 2-4 puffs of albuterol or positive methacholine challenge (20% fall in FEV1 at less than 8 mg/ml) - either of these can available from the previous 2 years * Generally good health
Exclusion criteria
* Oral corticosteroid use within the past 3 months * Use of high dose inhaled corticosteroids (greater than 500 mcg of fluticasone per day or greater) * Current or former smoker (quit less than 6 months prior to study enrollment or greater than 10 pack years) * Recent asthma exacerbation (within 6 weeks) * Current consumption of soy isoflavone supplements * Known adverse reaction to genistein, other phytoestrogens, or soy products * Pregnant * Unintentional weight loss of more than 10 pounds within the year * Major or unstable medical condition * Use of an investigational drug in the previous 30 days
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Exhaled Nitric Oxide | 0 and 4 weeks | Exhaled nitric oxide at baseline (week 0) and at 4 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Eosinophil LTC4 Synthesis | 0 and 4 weeks | Peripheral blood eosinophils were isolated before and after treatment with Novasoy, stimulated with calcium ionophore, and the amount of leukotriene C4 (LTC4) produced was measured by EIA. |
| Forced Expiratory Volume in One Second (FEV1) | 0 and 4 weeks | Forced expiratory volume in one second (FEV1) measured as liters/second |
Countries
United States
Participant flow
Recruitment details
Patients with asthma were recruited from Northwestern's medical clinics and by advertisements in the community.
Pre-assignment details
Patients with asthma were included in the study if they had mild-to-moderate disease not fully controlled on their current treatment.
Participants by arm
| Arm | Count |
|---|---|
| Soy Isoflavone Supplement This is a single blind study in which each participant was evaluated at baseline and then after receiving 100 mg of Novasoy once daily for 4 weeks. | 13 |
| Total | 13 |
Baseline characteristics
| Characteristic | Soy Isoflavone Supplement |
|---|---|
| Age Categorical <=18 years | 0 participants |
| Age Categorical >=65 years | 0 participants |
| Age Categorical Between 18 and 65 years | 15 participants |
| Age Continuous | 37.7 years STANDARD_DEVIATION 12.1 |
| Gender Female | 7 participants |
| Gender Male | 8 participants |
| Region of Enrollment United States | 15 participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 15 |
| serious Total, serious adverse events | 0 / 15 |
Outcome results
Primary
Exhaled Nitric Oxide
Exhaled nitric oxide at baseline (week 0) and at 4 weeks
Time frame: 0 and 4 weeks
Population: Per protocol
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Soy Isoflavone Supplement | Exhaled Nitric Oxide | Baseline | 67.0 parts per billion (ppb) | Standard Deviation 54.6 |
| Soy Isoflavone Supplement | Exhaled Nitric Oxide | 4 weeks | 54.8 parts per billion (ppb) | Standard Deviation 49.2 |
Comparison: The two groups tested were baseline and after 4 weeks of treatment with the soy isoflavone supplement.p-value: <0.03t-test, 2 sided
Secondary
Eosinophil LTC4 Synthesis
Peripheral blood eosinophils were isolated before and after treatment with Novasoy, stimulated with calcium ionophore, and the amount of leukotriene C4 (LTC4) produced was measured by EIA.
Time frame: 0 and 4 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Soy Isoflavone Supplement | Eosinophil LTC4 Synthesis | Baseline | 3.11 ng/ml | Standard Deviation 1.63 |
| Soy Isoflavone Supplement | Eosinophil LTC4 Synthesis | 4 weeks | 2.07 ng/ml | Standard Deviation 1.17 |
Comparison: The two groups tested were baseline and after 4 weeks of treatment with the soy isoflavone supplement.p-value: 0.02t-test, 2 sided
Secondary
Forced Expiratory Volume in One Second (FEV1)
Forced expiratory volume in one second (FEV1) measured as liters/second
Time frame: 0 and 4 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Soy Isoflavone Supplement | Forced Expiratory Volume in One Second (FEV1) | Baseline | 2.59 liters/sec | Standard Deviation 0.77 |
| Soy Isoflavone Supplement | Forced Expiratory Volume in One Second (FEV1) | 4 weeks | 2.56 liters/sec | Standard Deviation 0.92 |
Comparison: The two groups tested were baseline and after 4 weeks of treatment with the soy isoflavone supplement.p-value: 0.88t-test, 2 sided