Genes, Soy Isoflavones, and Virus - Preventing Airway Remodeling, Asthma, and Wheezing Study
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Eos3 transcriptional module expression
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 4 Months 至 24 Months（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Parent or guardian must be an adult (≥18 years of age) and able to understand and provide informed consent.
- •Age: Term infants (≥37 weeks) aged 4 months to 24 months at recruitment.
- •Admitted to Lurie Children's Hospital or presenting to ED for an acute viral lower respiratory tract infection within 1-3 days of onset.
排除标准
- •Inability or unwillingness of a parent or guardian to give written informed consent or comply with study protocol
- •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)
- •Currently on a soy based formula as determined by the judgement of the study investigators
- •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.
- •On provider prescribed treatment for recurrent wheezing such as regular or intermittent inhaled steroids
- •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).
- •Medication use:
- •Maternal use of tamoxifen during pregnancy or breastfeeding
- •Use of immunomodulatory medications such as methotrexate, mycophenolate, azathioprine, or other immunomodulatory agent in the mother if breastfeeding or in the infant.
- •Use of another investigational agent in the last 30 days prior
- •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
- •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.
- •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
- •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.
- •Any chronic condition requiring use of systemic corticosteroids or another immunomodulating agent prior to visit 1 (V1).
- •Non-adherence:
- •Inability / unwillingness of the parents to facilitate ingestion of the investigational product
- •Unwillingness of the parents to allow the staff to perform baseline procedures of nasal swabs
- •Participant is in foster care or is a ward of the state.
- •Caregiver does not have access to a phone (needed for scheduling appointments or responding to questionnaires)
- •Plan(s) for the family to move from the area during the study period
- •The infant's caretaker does not primarily speak English or Spanish.
研究组 & 干预措施
observational arm for more severe subjects
these subjects will have endotyping carried out by nasal swab at presentation and day 7
soy isoflavone
soy isoflavone at 1.5 mg/kg divided bid dosed from presentation for 2 - 3 day sof dosing
干预措施: Soy Isoflavone Nutritional Supplements (Drug)
结局指标
主要结局
Eos3 transcriptional module expression
时间窗: 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
次要结局
- Th2 and epithelial module expression(day 4-7 of illness)