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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if soy isoflavones, a type of dietary supplement, can reduce asthma risk in children with a specific genetic variation that causes higher levels of a protein linked to inflammation. Researchers seek to find out if soy isoflavones can decrease the number of children with a specific asthma-related immune response and reduce wheezing episodes when administered in their first year. Participants will take either soy isoflavones or a placebo, mixed into food or drink, twice daily for seven months. Families with infants who have a family history of asthma or have been diagnosed with atopic dermatitis may be suitable candidates. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to significant findings in asthma prevention.

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.

Is there any evidence suggesting that soy isoflavones are likely to be safe for humans?

Research has shown that soy isoflavones are generally safe for consumption. Studies have found that these supplements have side effects similar to those of common dietary supplements. Some individuals might experience mild stomach issues, though this is uncommon. While soy isoflavones have not demonstrated strong benefits for asthma, they are usually well-tolerated. However, research on their safety during pregnancy or breastfeeding, especially at higher doses, remains insufficient. Overall, soy isoflavones appear to be a safe choice for most people, but monitoring for any changes or side effects and consulting a healthcare provider is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for asthma?

Unlike the standard asthma treatments, which often include inhalers or corticosteroids, soy isoflavones are derived from soybeans and offer a more natural approach. Researchers are excited about this treatment because soy isoflavones might reduce inflammation in the airways by acting as antioxidants. This unique mechanism of action could provide a complementary option for asthma management, especially for individuals looking for plant-based alternatives.

What evidence suggests that soy isoflavones might be an effective treatment for asthma?

This trial will compare soy isoflavones with a placebo to assess their potential benefits for asthma. Research shows that soy isoflavones might reduce severe asthma attacks. Some studies suggest that people taking soy isoflavones had better lung function than those who did not. However, other research found no significant improvement in lung function or asthma symptoms. These mixed results indicate that while some evidence supports benefits for asthma control, other studies do not show a clear advantage. Overall, the potential of soy isoflavones to treat asthma remains under investigation, and more research is needed to determine their effectiveness. ^{2 6 7 8 9}

Who Is on the Research Team?

Rajesh Kumar, MD

Principal Investigator

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

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/26010632/

Effect of a soy isoflavone supplement on lung function and ... Some data suggest that supplementation with soy isoflavone may be an effective treatment for patients with poor asthma control.

2. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/2297169

Effect of a Soy Isoflavone Supplement on Lung Function ... Some data suggest that supplementation with soy isoflavone may be an effective treatment for patients with poor asthma control. Objective To ...

3. news.feinberg.northwestern.edu news.feinberg.northwestern.edu/2015/05/26/soy-supplements-do-not-improve-asthma/

Soy Supplements Do Not Improve Asthma - News Center Smith and colleagues previously noticed that asthmatics taking soy isoflavone had better lung functioning than their counterparts.

4. jacionline.org jacionline.org/article/S0091-6749(19)30117-4/pdf

Soy isoflavones reduce asthma exacerbation in asthmatic ... Conclusions: This study demonstrates that soy isoflavone treatment provides a significant benefit in reducing the number of severe asthma ...

5. jwatch.org jwatch.org/na38008/2015/06/02/soy-isoflavones-arent-helpful-treating-asthma-patients

Soy Isoflavones Aren't Helpful in Treating Asthma Patients After 24 weeks, the two groups exhibited similar lung function, asthma symptoms, and exhaled nitric oxide levels, despite a marked increase in ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5443623/

Effect of a Soy Isoflavone Supplement on Lung Function ... Some data suggest that supplementation with soy isoflavone may be an effective treatment for patients with poor asthma control.

7. vkm.no vkm.no/download/18.645b840415d03a2fe8f25c54/1502712224209/Risk%20assessment%20of%20%22other%20substances%22%20%E2%80%93%20Isoflavones%20from%20soy.pdf

Risk assessment of "other substances" – Isoflavones from soy The authors concluded that phytoestrogens supplements had a safe side-effect profile with moderately elevated rates of gastrointestinal side ...

8. verywellhealth.com verywellhealth.com/isoflavones-benefits-side-effects-dosage-and-interactions-4687017

Benefits and Risks of Taking Isoflavones There is not enough clinical research data to support the safe use of soy products when pregnant or breastfeeding, particularly at higher doses.

9. alzdiscovery.org alzdiscovery.org/uploads/cognitive_vitality_media/Soy_isoflavones_UPDATE_(supplement).pdf

Soy Isoflavones Safety: Soy isoflavone intake via diet or supplementation is regarded as safe with a side effect profile that is similar to what is experienced ...