The Study of Soy Isoflavones in Asthma

Asthma is a common disease that has a major impact on morbidity and health care costs.
Although the prevalence and severity of asthma have increased over the last several decades,
the specific causes remain unknown. One possible mechanism is a change in diet. Yet,
epidemiological and interventional studies designed to identify a key nutrient or
antioxidant vitamin that may be responsible for the increase in disease severity have
produced inconsistent results. A recent pilot study showed a soy isoflavone supplement
reduces exhaled nitric oxide (FeNO) and ex vivo LTC4 synthesis in patients with inadequately
controlled asthma. This clinical trial is designed to test the novel hypothesis that dietary
supplementation with soy isoflavones is an effective treatment in patients with poorly
controlled asthma. The study will include 380 patients with low dietary soy intake, 12 years
of age or older, who are taking either inhaled corticosteroids or leukotriene modifiers and
have inadequately controlled asthma. Participants will be randomly assigned to treatment
with either a soy isoflavone supplement (containing genistein, daidzein and glycitein; 100
mg daily of the glycoside forms) or placebo for six months. The results of this trial will
increase understanding of the role of diet in asthma; could identify a novel, safe and
relatively inexpensive treatment for patients with asthma; and potentially will have a
substantial impact on public health in the United States.

Inclusion Criteria:

- Age 12 or older

- Physician diagnosed asthma

- FEV1 equal or greater than 50% predicted pre-bronchodilator

- At least 12% increase in FEV1 15-3 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 be available from the previous 2 years

- Currently prescribed daily controller asthma medication

- Poor asthma control (at least one of the following)

- A score of 1.5 or greater on the Juniper Asthma Control Questionnaire

- Use of beta-agonist for asthma symptoms two or more times per week

- Nocturnal awakening with asthma symptoms more than once per week

- Two or more episodes of asthma symptoms in the past 12 months with each
requiring at least one of the following: emergency department visit, unscheduled
physician visit, prednisone course, hospitalization

- Smoking status

- Non-smoker for 6 months or longer

- Less than 10 pack-years smoking history

Exclusion Criteria:

- Pulmonary function

- FEV1 less than 50% predicted pre-bronchodilator

- Other major chronic illnesses

- Conditions which in the judgment of the study physician would interfere with
participation in the study, e.g., non-skin cancer, endocrine disease, coronary
artery disease, severe hypertension, immunodeficiency states

- History of thyroid disease, breast cancer, ovarian, or endometrial cancer

- History of physician diagnosis of chronic bronchitis, emphysema, or COPD

- Medication use

- Current consumption of soy isoflavone supplements

- Oral corticosteroid use within the past 6 weeks

- Use of tamoxifen

- Use of an investigational treatment in the previous 30 days

- "Drug" allergy

- Known adverse reaction to genistein, other phytoestrogens, or soy products

- Females of childbearing potential

- Pregnant or lactating. Participants must agree to use effective contraception
during the trial.

- Non-adherence

- Inability or unwillingness to provide consent or, in the case of children,
inability or unwillingness of the child to provide assent

- Inability to swallow study medication

- Inability to perform baseline measurements

- Completion of less than 10 of the last 14 days diary entries during screening
period

- Inability to be contacted by telephone

- Intention to move out of the area within 6 months

- Other

- Recent asthma exacerbation (within 6 weeks)

- Recent upper respiratory infection (within 2 weeks)

- Body weight less than 77 pounds (35 kg)

- Intake of soy or soy-enriched foods 1 or more times a week

- Change in diet over the past month or expected change in diet during the study