Soy Isoflavones for Asthma

(SIRA Trial)

Recruiting at 1 trial location

Overseen By Sarah Godley, RN

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: Rajesh Kumar

Must not be taking: Immunomodulatory agents, Inhaled steroids

Disqualifiers: Soy formula, Thyroid disease, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 5

Duration: 7 months

65 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this clinical trial is to compare soy isoflavones to placebo in children who at risk of asthma and have a genetic variation which results in them making more of a pro-inflammatory protein, plasminogen activator inhibitor-1. The main questions this trail seeks to answer is: will soy isoflavones decrease the proportion of infants with aT2 high endotype at the end of treatment, and secondarily decrease the number of wheezing episodes in these children when given in the first year of life. Participants will be asked to ingest soy isoflavone or placebo twice daily mixed into a liquid or puree vehicle for 7 months from randomization. There will be 3 mandatory in-person visits, and 6 virtual visits in the first year. There will also be 11 monthly questionnaires and 1 in person visit in the observation year. Participants will have 4 nasal swabs, 3 blood draws, and also provide 4 stool samples over the course of the study.

Will I have to stop taking my current medications?

The trial requires that participants do not use certain medications. Specifically, infants cannot be on treatment for recurrent wheezing like regular inhaled steroids, and neither the mother nor the infant can use immunomodulatory medications. If the mother is breastfeeding, she cannot use tamoxifen or certain other medications.

What data supports the effectiveness of the treatment Soy Isoflavones for Asthma?

Research suggests that soy isoflavones, particularly genistein, may improve lung function in asthma patients by reducing inflammation and airway hyperresponsiveness. Studies have shown that people who consume more genistein tend to have better lung function, and animal studies indicate that soy isoflavones can reduce airway inflammation and mucus production. ^{1 2 3 4 5}

Is it safe for humans to take soy isoflavones or genistein?

The research does not specifically address the safety of soy isoflavones or genistein, but they are commonly used in supplements for various conditions, suggesting they are generally considered safe. However, more studies are needed to confirm their safety in humans. ^{1 2 3 5 6}

How does the treatment with soy isoflavones differ from other asthma treatments?

Soy isoflavones, particularly genistein, are unique in asthma treatment because they have anti-inflammatory effects and can improve lung function by inhibiting certain inflammatory processes in the airways, unlike traditional asthma medications that primarily focus on bronchodilation or corticosteroid effects. ^{1 2 3 4 5}

Research Team

Rajesh Kumar, MD

Principal Investigator

Ann and Robert H. Lurie Children's Hospital of Chicago

Eligibility Criteria

This trial is for full-term infants born within specific dates, who are at risk for asthma and have a genetic variation linked to inflammation. They must have a family history of asthma or related conditions, or the child must have been diagnosed with atopic dermatitis. Parents need to consent and participate in several visits and tests.

Inclusion Criteria

My child was born full-term between January 1 and May 15 of this year.

Parent guardian must be able to understand and provide informed consent

My genetic test shows I have the PAI-1 risk allele.

Exclusion Criteria

I am breastfeeding and either I or my baby is on immune system medications.

Inability or unwillingness of a parent guardian to give written informed consent or comply with study protocol

Currently on a soy based formula

Timeline

Screening

Participants are screened for eligibility to participate in the trial

Up to 6 months

1 visit (in-person)

Treatment

Participants receive soy isoflavone or placebo twice daily for 7 months

7 months

3 visits (in-person), 6 visits (virtual)

Observation

Participants are monitored for wheezing episodes and other respiratory outcomes

1 year

1 visit (in-person), 11 monthly questionnaires

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Soy Isoflavones

Trial Overview The study compares soy isoflavones with a placebo in preventing wheezing in high-risk infants during their first year. Infants will take the treatment twice daily for 7 months, attend physical and virtual check-ups, answer monthly questionnaires, and provide nasal swabs, blood samples, and stool samples.

Participant Groups

Group I: Soy isoflavone Experimental Treatment 1 Intervention

Soy isoflavone powder dosed in puree or liquid twice daily

Group II: Placebo Placebo Group 2 Interventions

Matching placebo powder dosed in puree or liquid twice daily

Who Is Running the Clinical Trial?

Rajesh Kumar

Lead Sponsor

Trials

1

Recruited

70+

Northwestern University

Collaborator

Trials

1,674

Recruited

989,000+

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborator

Trials

3,361

Recruited

5,516,000+

University of Colorado, Denver

Collaborator

Trials

1,842

Recruited

3,028,000+

University of South Florida

Collaborator

Trials

433

Recruited

198,000+

Findings from Research

Genistein, a soy isoflavone, effectively inhibits the synthesis of leukotriene C(4) (LTC(4)) in eosinophils, which is linked to asthma inflammation, by blocking specific signaling pathways (p38 MAP kinase and MAPKAP-2).

A 4-week dietary supplementation of 100 mg/day of soy isoflavones in asthma patients led to a significant 33% reduction in eosinophil LTC(4) production and an 18% decrease in exhaled nitric oxide, indicating reduced eosinophilic inflammation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A mechanism of benefit of soy genistein in asthma: inhibition of eosinophil p38-dependent leukotriene synthesis. Kalhan, R., Smith, LJ., Nlend, MC., et al.[2023]

In a study of 300 patients with inadequately controlled asthma, those with moderate to high intake of soy genistein showed better lung function (higher FEV1) compared to those with little or no intake.

Participants with low genistein intake experienced more episodes of poor asthma control, suggesting that dietary soy genistein may play a beneficial role in managing asthma symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of dietary soy genistein intake with lung function and asthma control: a post-hoc analysis of patients enrolled in a prospective multicentre clinical trial. Bime, C., Wei, CY., Holbrook, J., et al.[2021]

In a study of 1,033 participants aged 12-75, higher intake of genistein, a soy isoflavone, was linked to better lung function in asthma patients, with significant improvements in forced expiratory volume (FEV1) and peak expiratory flow (PEF).

No other nutrients evaluated showed a consistent relationship with asthma severity or exacerbation rates, suggesting that genistein may be a unique dietary factor worth further investigation for its potential to improve asthma outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dietary intake of soy genistein is associated with lung function in patients with asthma. Smith, LJ., Holbrook, JT., Wise, R., et al.[2019]

In a murine model of asthma, oral administration of soy isoflavone significantly reduced airway hyperresponsiveness and inflammation, as evidenced by decreased eosinophil counts and improved lung function after ovalbumin exposure.

Soy isoflavone also modulated inflammatory biomarkers, increasing levels of interferon (IFN)-γ while decreasing interleukin (IL)-4 and IL-5, suggesting its potential as a nutritional supplement for treating airway inflammatory diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibition of airway inflammation, hyperresponsiveness and remodeling by soy isoflavone in a murine model of allergic asthma. Bao, ZS., Hong, L., Guan, Y., et al.[2023]

A study involving 386 participants with poorly controlled asthma found that a soy isoflavone supplement did not significantly improve lung function or asthma control compared to a placebo after 24 weeks.

Despite an increase in plasma genistein levels in those taking the supplement, the results indicate that soy isoflavones should not be recommended for asthma management in patients already on controller medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of a soy isoflavone supplement on lung function and clinical outcomes in patients with poorly controlled asthma: a randomized clinical trial. Smith, LJ., Kalhan, R., Wise, RA., et al.[2018]

In a murine asthma model, genistein significantly reduced airway inflammation and altered the balance of T helper cytokines by decreasing Th2-type cytokines and increasing Th1-type cytokines.

Genistein's mechanism of action appears to involve the down-regulation of GATA-3 and STAT-6, which are associated with Th2 responses, and the up-regulation of T-bet, which is linked to Th1 responses, suggesting it may effectively modulate immune reactions in asthma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genistein attenuated allergic airway inflammation by modulating the transcription factors T-bet, GATA-3 and STAT-6 in a murine model of asthma. Gao, F., Wei, D., Bian, T., et al.[2014]

References

1. England pubmed.ncbi.nlm.nih.gov

A mechanism of benefit of soy genistein in asthma: inhibition of eosinophil p38-dependent leukotriene synthesis. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Association of dietary soy genistein intake with lung function and asthma control: a post-hoc analysis of patients enrolled in a prospective multicentre clinical trial. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Dietary intake of soy genistein is associated with lung function in patients with asthma. [2019]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Inhibition of airway inflammation, hyperresponsiveness and remodeling by soy isoflavone in a murine model of allergic asthma. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Effect of a soy isoflavone supplement on lung function and clinical outcomes in patients with poorly controlled asthma: a randomized clinical trial. [2018]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Genistein attenuated allergic airway inflammation by modulating the transcription factors T-bet, GATA-3 and STAT-6 in a murine model of asthma. [2014]