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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.

연구 개요

상태

아직 모집하지 않음

정황

개입 / 치료

상세 설명

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.

연구 유형

중재적

등록 (추정된)

60

단계

  • 2 단계
  • 1단계

연락처 및 위치

이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.

연구 연락처

연구 연락처 백업

연구 장소

    • Illinois
      • Chicago, Illinois, 미국, 60311

참여기준

연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.

자격 기준

공부할 수 있는 나이

  • 어린이

건강한 자원 봉사자를 받아들입니다

아니

설명

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.

공부 계획

이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.

연구는 어떻게 설계됩니까?

디자인 세부사항

  • 주 목적: 치료
  • 할당: 무작위화되지 않음
  • 중재 모델: 단일 그룹 할당
  • 마스킹: 없음(오픈 라벨)

무기와 개입

참가자 그룹 / 팔
개입 / 치료
실험적: 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
간섭 없음: observational arm for more severe subjects
these subjects will have endotyping carried out by nasal swab at presentation and day 7

연구는 무엇을 측정합니까?

주요 결과 측정

결과 측정
측정값 설명
기간
Eos3 transcriptional module expression
기간: 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

2차 결과 측정

결과 측정
측정값 설명
기간
Th2 and epithelial module expression
기간: 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

공동 작업자 및 조사자

여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.

스폰서

수사관

  • 수석 연구원: Rajesh Kumar, MD, MSCI, Ann & Robert H Lurie Children's hospital of Chicago

연구 기록 날짜

이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.

연구 주요 날짜

연구 시작 (추정된)

2026년 10월 1일

기본 완료 (추정된)

2027년 12월 31일

연구 완료 (추정된)

2028년 6월 30일

연구 등록 날짜

최초 제출

2026년 9월 14일

QC 기준을 충족하는 최초 제출

2026년 9월 14일

처음 게시됨 (실제)

2026년 9월 18일

연구 기록 업데이트

마지막 업데이트 게시됨 (실제)

2026년 9월 18일

QC 기준을 충족하는 마지막 업데이트 제출

2026년 9월 14일

마지막으로 확인됨

2026년 9월 1일

추가 정보

이 연구와 관련된 용어

기타 연구 ID 번호

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

개별 참가자 데이터(IPD) 계획

개별 참가자 데이터(IPD)를 공유할 계획입니까?

예

IPD 계획 설명

Data will be available on request after publication.

IPD 공유 기간

de-identified data will be available after study close.

IPD 공유 액세스 기준

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

IPD 공유 지원 정보 유형

  • 연구_프로토콜

약물 및 장치 정보, 연구 문서

미국 FDA 규제 의약품 연구

예

미국 FDA 규제 기기 제품 연구

아니

이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .