Soy Isoflavones For Inner City Infants At Risk For Asthma (SIRA) Study

Prior treatment

• Parents who will not include either a puree or some form of bottle feeding such that the infant would be able to take the investigational product in a puree or a liquid (expressed breast milk, supplemental formula, or a small amount of water).
• Currently on a soy based formula.
• On treatment for recurrent wheezing such as regular inhaled steroids.
• Medication use
  • Maternal use of tamoxifen in pregnancy or if breastfeeding
  • Use of immunomodulatory medications such at methotrexate, mycophenolate, azathioprine, or other immunomodulatory agent in the mother if breastfeeding or in the infant.
• Use of another investigational agent in the last 30 days prior to randomization.
• Known allergy to soy protein (either by reported allergy or skin testing to soy prior to randomization) or reported allergy to NovaSoy, from which the investigational product is compounded.
• The infant is currently participating in another asthma-related pharmaceutical study or intervention study or who have participated in another asthma-related pharmaceutical study or intervention study in the month prior to enrollment.
• Infant requiring intubation prior to screening.
• Infant requiring \> 3 hospitalizations for asthma symptoms/ wheezing illness prior to screening.
• Infant requiring \> 3 five day bursts of oral steroid at least 14 days apart from each other prior to screening.
• Non-adherence:
  • Inability / unwillingness of the parents to induce the infant to swallow study medication
  • Unwillingness of the parents to allow the staff to perform baseline measurements
• Cannot have had more than two wheezing / "asthma" episodes (separated from each other by at least 14 days), each requiring at least a 5 day course of oral steroids in the time between screening visit A (V1) and randomization (V3).

Other illness

• The infant may not have the following specific contraindications: known congenital thyroid disease, or a history of estrogen sensitive clinically relevant mutations in the family (such as BRCA1).
• Current, parent reported, diagnosis of mental illness or current, diagnosed or self-reported drug or alcohol abuse (in the primary caregiver) that, in the opinion of the investigator, would interfere with the participant's ability to comply with study requirements.
• Any chronic condition requiring use of systemic corticosteroids or another immunomodulating agent at screening or before randomization, and during the course of the study.

Lab values

• Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study.

Age

• Must be ≥4 months and \<12 months of age at randomization

Other

• 1\. Inability or unwillingness of a parent or guardian to give written informed consent or comply with study protocol.
• Breastfeeding mothers who are taking soy supplements or soy enriched foods more than 2 times a week and will not stop this level of ingestion while breastfeeding.
• Living with a foster parent as a ward of the state.
• Caregiver does not have access to a phone (needed for scheduling appointments or responding to questionnaires).
• Plan(s) for the family to move from the area during the study period.
• The infant's caretaker does not primarily speak English or Spanish.
  • In order to be eligible to continue in the study following screening visit A (V1) , an individual must meet all of the following additional randomization criteria:
• Must have either 4G/4G or 4G/5G genotype
• Cannot have had a severe wheezing exacerbation requiring ICU admission between screening (V1) and randomization (V3)

• Parent/guardian must be an adult (≥18 years of age) and able to understand and provide informed consent.
• Age: Term infants (≥37 weeks gestational age) less than 12 months of age at recruitment
• High risk of asthma: As determined by one or more of the following:
  • A history of uni- or bi-parental asthma with onset in childhood by parent self report, OR
  • Uni- or bi-parental asthma with onset after childhood along with the presence of one or more other comorbid atopic condition including allergic rhinitis, atopic dermatitis, or food allergy, OR
  • atopic dermatitis in the child determined by parent report of a physician diagnosis
• Genotype: Either homozygous or heterozygous for the PAI-1 risk allele (i.e. 4G4G or 4G5G).
• Have a primary place of residence in one of the pre-selected recruitment census tracts as outlined in the SIRA Manual of Operations (MOP).
  • Participants who do not live in the pre-selected census tracts but live within the Office of Management and Budget (OMB) defined Metropolitan Statistical Area and have publicly funded health insurance will qualify for inclusion.