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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.

調査の概要

状態

まだ募集していません

条件

詳細な説明

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.

研究の種類

介入

入学 (推定)

60

段階

  • フェーズ2
  • フェーズ 1

連絡先と場所

このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。

研究連絡先

研究連絡先のバックアップ

研究場所

    • Illinois
      • Chicago、Illinois、アメリカ、60311
        • Ann & Robert H Lurie Children's hospital of Chicago
        • コンタクト:
        • コンタクト:

参加基準

研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。

適格基準

就学可能な年齢

  • 子

健康ボランティアの受け入れ

いいえ

説明

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.

研究計画

このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。

研究はどのように設計されていますか?

デザインの詳細

  • 主な目的:処理
  • 割り当て:非ランダム化
  • 介入モデル:単一グループの割り当て
  • マスキング:なし(オープンラベル)

武器と介入

参加者グループ / アーム
介入・治療
実験的: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
介入なし:observational arm for more severe subjects
these subjects will have endotyping carried out by nasal swab at presentation and day 7

この研究は何を測定していますか?

主要な結果の測定

結果測定
メジャーの説明
時間枠
Eos3 transcriptional module expression
時間枠: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

二次結果の測定

結果測定
メジャーの説明
時間枠
Th2 and epithelial module expression
時間枠: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

協力者と研究者

ここでは、この調査に関係する人々や組織を見つけることができます。

捜査官

  • 主任研究者:Rajesh Kumar, MD, MSCI、Ann & Robert H Lurie Children's hospital of Chicago

研究記録日

これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。

主要日程の研究

研究開始 (推定)

2026年10月1日

一次修了 (推定)

2027年12月31日

研究の完了 (推定)

2028年6月30日

試験登録日

最初に提出

2026年9月14日

QC基準を満たした最初の提出物

2026年9月14日

最初の投稿 (実際)

2026年9月18日

学習記録の更新

投稿された最後の更新 (実際)

2026年9月18日

QC基準を満たした最後の更新が送信されました

2026年9月14日

最終確認日

2026年9月1日

詳しくは

本研究に関する用語

その他の研究ID番号

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

個々の参加者データ (IPD) の計画

個々の参加者データ (IPD) を共有する予定はありますか?

はい

IPD プランの説明

Data will be available on request after publication.

IPD 共有時間枠

de-identified data will be available after study close.

IPD 共有アクセス基準

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

IPD 共有サポート情報タイプ

  • STUDY_PROTOCOL

医薬品およびデバイス情報、研究文書

米国FDA規制医薬品の研究

はい

米国FDA規制機器製品の研究

いいえ

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