Genes, Soy Isoflavones, and Virus (GSV)

Genes, Soy Isoflavones, and Virus - Preventing Airway Remodeling, Asthma, and Wheezing Study

In this study, we will assess whether children without established asthma who have a variation in the switch for the PAI-1 gene will have higher PAI-1 levels and remodeling / allergic inflammatory pathways in their airways than children who do not have the gene. We will also determine if soy isoflavones given when presenting for an acute respiratory illness can decrease these changes.

Study Overview

• Status: Not yet recruiting
• Conditions: Wheezing
• Intervention / Treatment: Drug: Soy Isoflavone Nutritional Supplements

Detailed Description

Pediatric asthma affects 8.3% of U.S. children, accounting for 5.92 billion dollars of U.S. health care expenditure annually. Approximately 80% of the children who progress to have asthma will have wheeze in early childhood, suggesting that primary prevention should target infancy. In particular, severe early life viral lower respiratory tract infection (LRTI) shows strong associations with asthma development which are modified by genetic predisposition.1-5 A gain of function plasminogen activator inhibitor-1 (PAI-1) promoter variant is present in up to 60% of the population who develop asthma in either homozygote or heterozygote form. If children with ≥1 copy of the PAI-1 risk allele had a respiratory viral illness requiring a physician visit before 2 years old, these subjects had a 12-fold (any virus) to 18-fold (self-reported Respiratory Syncytial Virus (RSV)) increased risk of developing asthma. PAI-1 production increases in the airway at the time of a viral illness and promotes both fibrosis and an allergic airway milieu. We have found that soy isoflavones decrease the production of PAI-1 and decrease rates of asthma exacerbations by 75% in subjects with the risk gene. This pilot will allow for preliminary data to determine if on-demand treatment with soy isoflavone improves epithelial integrity and decreases Th2 airway responses if dosed with onset of illness. This would establish the viability of on demand treatment for early life viral illness which may modulate acute outcomes. In this study, we will assess whether children without established asthma who have the PAI-1 genotype will have higher PAI-1 levels and remodeling / allergic inflammatory pathways in their airways than children who do not have the genotype. We will also determine if soy isoflavones given when presenting for an acute respiratory illness can decrease these changes in children both with and without the genotype. Finally, we will also study these questions in a lung organoid / Air Liquid Interface (ALI) model with cells from subjects with the risk allele, which will allow us to compare soy isoflavone pre-inoculation treatment with treatment post infection in a controlled experiment. These data would be essential to set up the team to assess the effects of on demand treatment of children with LRTI irrespective of asthma after presentation to the ED. This would be an important step forward compared to chronic treatment in high-risk populations which will have barriers to implementation.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Caroline Merck, MPH; Phone Number: 312-227-2469; Email: cmerck@luriechildrens.org
• Study Contact Backup: Name: Aliviya Schulze, BS; Phone Number: 312-227-5391; Email: aschulze@luriechildrens.org

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60311
      • Ann & Robert H Lurie Children's hospital of Chicago
      • Contact: Aliviya Schulze, BS; Phone Number: 312-227-5391; Email: aschulze@luriechildrens.org
      • Contact: Caroline Merck, MS; Phone Number: 312-227-2469; Email: cmerck@luriechildrens.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Parent or guardian must be an adult (≥18 years of age) and able to understand and provide informed consent.
2. Age: Term infants (≥37 weeks) aged 4 months to 24 months at recruitment.
3. Admitted to Lurie Children's Hospital or presenting to ED for an acute viral lower respiratory tract infection within 1-3 days of onset.

Exclusion Criteria:

1. Inability or unwillingness of a parent or guardian to give written informed consent or comply with study protocol
2. 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)
3. Currently on a soy based formula as determined by the judgement of the study investigators
4. 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 (assessed by soy intake questionnaire). Note there is no coercion to change dietary practices. This is simply an exclusion criteria if the mother does not want to limit soy intake to this level for the time of the study.
5. On provider prescribed treatment for recurrent wheezing such as regular or intermittent inhaled steroids
6. 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).

7. Medication use:

   1. Maternal use of tamoxifen during pregnancy or breastfeeding
   2. Use of immunomodulatory medications such as methotrexate, mycophenolate, azathioprine, or other immunomodulatory agent in the mother if breastfeeding or in the infant.
8. Use of another investigational agent in the last 30 days prior
9. Current parent reported diagnosis of mental illness or current 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
10. Known allergy to soy protein (either by reported allergy or prior positive allergy results and no history of ongoing ingestion) or reported allergy to NovaSoyTM, from which the investigational product is compounded.
11. The infant is currently participating in another allergic disease (asthma, food allergy, or AD) -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
12. 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.
13. Any chronic condition requiring use of systemic corticosteroids or another immunomodulating agent prior to visit 1 (V1).

14. Non-adherence:

    1. Inability / unwillingness of the parents to facilitate ingestion of the investigational product
    2. Unwillingness of the parents to allow the staff to perform baseline procedures of nasal swabs
15. Participant is in foster care or is a ward of the state.
16. Caregiver does not have access to a phone (needed for scheduling appointments or responding to questionnaires)
17. Plan(s) for the family to move from the area during the study period
18. The infant's caretaker does not primarily speak English or Spanish.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: soy isoflavone; soy isoflavone at 1.5 mg/kg divided bid dosed from presentation for 2 - 3 day sof dosing	Drug: Soy Isoflavone Nutritional Supplements; Soy isoflavone will be administered orally at a dose of 1.5 mg/ kg divided bid from presentation to day 7 of illness
No Intervention: observational arm for more severe subjects; these subjects will have endotyping carried out by nasal swab at presentation and day 7

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Eos3 transcriptional module expression	The mean expression level of the Th2 and ciliated epithelium (eos3) transcriptional module at day 4-7 of viral illness	on day 4-7 of illness after 2-3 days of dosing

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Th2 and epithelial module expression	This will include the mean expression level of other key transcriptional modules representing Th2 and epithelial processes, including expression of m24<squamous epithelium>, squa1 <tight junctions and epithelial integrity>, and m27 <TGFB/SMAD3 regulation of PAI-1> modules at day 4-7 of viral illness of viral illness	day 4-7 of illness

Collaborators and Investigators

• Sponsor: Ann & Robert H Lurie Children's Hospital of Chicago
• Investigators: Principal Investigator: Rajesh Kumar, MD, MSCI, Ann & Robert H Lurie Children's hospital of Chicago

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): June 30, 2028

Study Registration Dates

• First Submitted: September 14, 2026
• First Submitted That Met QC Criteria: September 14, 2026
• First Posted (Actual): September 18, 2026

Study Record Updates

• Last Update Posted (Actual): September 18, 2026
• Last Update Submitted That Met QC Criteria: September 14, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Keywords: soy isoflavone; PAI-1
• Additional Relevant MeSH Terms: Signs and Symptoms, Respiratory; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Respiratory Sounds
• Other Study ID Numbers: STUDY00001088 (University of Texas Health Science Center at San Antonio)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data will be available on request after publication.
• IPD Sharing Time Frame: de-identified data will be available after study close.
• IPD Sharing Access Criteria: all investigators who request access after publication of findings will have a deidentified dataset shared with them
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No