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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.

研究概览

地位

尚未招聘

条件

详细说明

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.

研究类型

介入性

注册 (估计的)

60

阶段

  • 阶段2
  • 阶段1

联系人和位置

本节提供了进行研究的人员的详细联系信息,以及有关进行该研究的地点的信息。

学习联系方式

研究联系人备份

学习地点

    • Illinois
      • Chicago、Illinois、美国、60311

参与标准

研究人员寻找符合特定描述的人,称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

  • 孩子

接受健康志愿者

不

描述

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.

学习计划

本节提供研究计划的详细信息,包括研究的设计方式和研究的衡量标准。

研究是如何设计的?

设计细节

  • 主要用途:治疗
  • 分配:非随机化
  • 介入模型:单组作业
  • 屏蔽:无(打开标签)

武器和干预

参与者组/臂
干预/治疗
实验性的:soy isoflavone
soy isoflavone at 1.5 mg/kg divided bid dosed from presentation for 2 - 3 day sof dosing
Soy isoflavone will be administered orally at a dose of 1.5 mg/ kg divided bid from presentation to day 7 of illness
无干预:observational arm for more severe subjects
these subjects will have endotyping carried out by nasal swab at presentation and day 7

研究衡量的是什么?

主要结果指标

结果测量
措施说明
大体时间
Eos3 transcriptional module expression
大体时间:on day 4-7 of illness after 2-3 days of dosing
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

次要结果测量

结果测量
措施说明
大体时间
Th2 and epithelial module expression
大体时间:day 4-7 of illness
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

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

调查人员

  • 首席研究员:Rajesh Kumar, MD, MSCI、Ann & Robert H Lurie Children's hospital of Chicago

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查,以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (估计的)

2026年10月1日

初级完成 (估计的)

2027年12月31日

研究完成 (估计的)

2028年6月30日

研究注册日期

首次提交

2026年9月14日

首先提交符合 QC 标准的

2026年9月14日

首次发布 (实际的)

2026年9月18日

研究记录更新

最后更新发布 (实际的)

2026年9月18日

上次提交的符合 QC 标准的更新

2026年9月14日

最后验证

2026年9月1日

更多信息

与本研究相关的术语

其他研究编号

  • STUDY00001088 (University of Texas Health Science Center at San Antonio)

计划个人参与者数据 (IPD)

计划共享个人参与者数据 (IPD)?

是的

IPD 计划说明

Data will be available on request after publication.

IPD 共享时间框架

de-identified data will be available after study close.

IPD 共享访问标准

all investigators who request access after publication of findings will have a deidentified dataset shared with them

IPD 共享支持信息类型

  • 研究方案

药物和器械信息、研究文件

研究美国 FDA 监管的药品

是的

研究美国 FDA 监管的设备产品

不

此信息直接从 clinicaltrials.gov 网站检索,没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求,请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改,我们的网站上也会自动更新.

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