MOdification Of THe Early-Life Respiratory Microbiome Through Vaginal SEEDing
试验速览
- 阶段
- 早期 1 期
- 状态
- 招募中
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Feasibility of the RCT
研究概览
简要总结
This is a single-center, parallel-arm, blind, sham-controlled, feasibility randomized controlled trial (RCT) to be conducted in healthy cesarean-born children. Eligible children will be randomized 1:1 to have their nose swabbed with either maternal vaginal secretions or a sterile swab (intervention vs. control group, respectively). The main hypothesis is that conducting an RCT assessing the utility of vaginal seeding in modifying the early-life upper respiratory tract (URT) microbiome of children born by cesarean section (C-section) is feasible and that the intervention is safe.
详细描述
Eligible children will be randomized 1:1 to have their nose swabbed with either maternal vaginal secretions or a sterile swab (intervention vs. control group, respectively). The procedure will be performed following birth by C-section and immediately after the initial newborn care by the general pediatric team. The mother and child will then receive usual medical care as determined by their health care providers. Follow-up will occur at multiple time points during the child's first 6 months of life. One planned interim analysis to assess the safety of the procedure will be conducted.
The intervention aims to transfer the maternal vaginal microbiome to the nasal cavity of cesarean-born children at birth (i.e., vaginal seeding of the URT). Hence, the intervention simply attempts to replicate the natural exposure to maternal vaginal secretions during vaginal delivery in children born by C-section.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Participants, the principal investigator (PI), co-investigators, data manager, and the lead biostatistician will be blinded to the actual group assignment until all statistical analyses of the data required to meet the primary and co-primary endpoints have occurred. The Data and Safety Monitoring Board will remain unmasked to actual group allocation throughout the pre-specified blinding period.
入排标准
- 年龄范围
- 18 Years 至 40 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •For the mother:
- •Female 18-40 years of age who is in good general health, is fully able to provide consent to participate in the study, anticipates being available for the duration of the study, and is willing to comply with all study procedures
- •Singleton pregnancy
- •Completed ≧3 prenatal care visits at Vanderbilt University Medical Center (any facility)
- •Having rectovaginal swabs collected at ≧36 weeks of gestation to screen for Group B Streptococcus (GBS) as part of prenatal screening tests
- •Having a scheduled (planned or non-emergency) C-section at Vanderbilt University Medical Center (main campus only)
- •No intent to relocate outside the middle Tennessee region within 12 months of recruitment
- •For the child:
- •Estimated gestational age ≧37 weeks
- •Birth weight ≧2,500 grams
排除标准
- •For the mother:
- •Past medical history of any of the following:
- •Previous child with GBS infection or prior positive GBS testing
- •Hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection
- •Genital herpes simplex virus (HSV) infection, genital herpetic lesions, or prior positive genital HSV testing
- •Genital human papilloma virus (HPV) infection, genital HPV lesions, or prior positive genital HPV testing
- •Diabetes type I or type II
- •Laboratory evidence during the current pregnancy of any of the following:
- •GBS bacteriuria in urine samples collected at any time (performed as standard of care)
- •GBS colonization in rectovaginal swabs collected at ≧36 weeks of gestation (performed as standard of care)
- •Chlamydia, trichomoniasis, or gonorrhea in urine samples collected at ≧36 weeks of gestation (performed as part of the screening procedures for this study)
- •Hepatitis B, hepatitis C, HIV, or syphilis in blood samples collected at ≧36 weeks of gestation (performed as part of the screening procedures for this study)
- •Uncontrolled gestational diabetes
- •Any serious obstetric disease (e.g., preeclampsia with severe features, placental abruption or severe bleeding, or thromboembolic disease) as deemed by the PI or co-investigators
- •Prior abnormal Pap smear
- •C-section scheduled for a genitourinary infection that would have interfered with vaginal delivery (e.g., genital herpetic lesions)
- •Lack of available prenatal screening tests
- •Use of systemic (i.e., oral, intramuscular, or intravenous) antibiotics in the 4 weeks prior to delivery (except for those being administered as part of the C-section)
- •Use of systemic (i.e., oral, intramuscular, or intravenous) immunosuppressive, biologic, or chemotherapeutic agents in the 3 months prior to delivery (except for systemic immunosuppressive agents not being used for their immunosuppressive effects [e.g., prenatal intramuscular beclomethasone for fetal lung maturation])
- •Fever (≧100.4°F [38°C]) in the 72 hours prior to delivery
- •Symptoms (e.g., dysuria, pruritus, or discharge) suggestive of a genitourinary infection (e.g., bacterial vaginosis, vaginal yeast infection, chorioamnionitis, or urinary tract infection) on the day of delivery
- •Symptoms (e.g., pain, tenderness, tingling, burning, itching, or swollen lymph nodes) suggestive of genital HSV infection on the day of delivery
- •Other symptoms (e.g., new-onset rhinorrhea, sore throat, cough, body aches, chills, nausea, vomiting, or diarrhea) suggestive of an acute infectious disease on the day of delivery
- •Physical exam findings (e.g., fever [≧100.4°F (38°C)] or vesicles, warts, or ulcers in the genital, perineal, or anal region) suggestive of a genitourinary infection on the day of delivery (performed as part of the screening procedures for this study if not performed as standard of care)
- •Maternal vaginal pH>4.5 on the day of delivery (performed as part of the screening procedures for this study)
- •Need for a switch from a scheduled C-section to an emergency C-section
- •Prelabor prolonged rupture of membranes (i.e., ≧18 hours prior to delivery)
- •Pregnancy as the result of an assisted reproductive technology or surrogacy
- •Participation in another clinical trial that involves an intervention that could impact the quality or interpretation of the study data as deemed by the PI or co-investigators
- •Other past or current medical problems that could compromise the safety of participants, interfere with their ability to comply with study requirements, or impact the quality or interpretation of the study data as deemed by the PI or co-investigators
- •For the child:
- •Need for neonatal measures outside routine clinical care (i.e., drying, tactile stimulation, bulb syringe or catheter suction of nose and mouth, or temperature maintenance) in the delivery room
- •Transfer to the neonatal intensive care unit immediately after delivery
- •Thick particulate meconium noted during delivery
- •Physical exam findings (e.g., tachypnea, nasal flaring, retractions, cyanosis, or grunting) suggestive of neonatal acute respiratory distress immediately after delivery (performed as part of the screening procedures for this study)
- •Prenatal diagnosis of a serious genetic, respiratory, cardiovascular, or neurological disease
- •Prenatal diagnosis of intrauterine growth restriction
- •Prenatal diagnosis of a major congenital anomaly (e.g., cleft lip or palate, cystic hygroma, or giant omphalocele)
- •Participation in another clinical trial that involves an intervention that could impact the quality or interpretation of the study data as deemed by the PI or co-investigators
- •Other past or current medical problems that could compromise the safety of participants, interfere with their ability to comply with study requirements, or impact the quality or interpretation of the study data as deemed by the PI or co-investigators
研究组 & 干预措施
Intervention Group
Vaginal Seeding
干预措施: Vaginal Seeding (Biological)
Control Group
Sterile Swab
干预措施: Sterile Swab (Other)
结局指标
主要结局
Feasibility of the RCT
时间窗: Six months following randomization
The study will be considered "definitively feasible as proposed," "possibly feasible as proposed," or "not feasible as proposed" based on eligibility, consent, enrollment, and loss to follow-up rates, which could be used as preliminary data to inform the design of a future phase II RCT. For this study, "enrolled" will be defined as consented and screened, with eligibility verified, and the eligibility, consent, enrollment, and loss to follow-up rates will be calculated using the following formulas: 1) eligibility rate = number of participants who are eligible\*100 / number of participants pre-screened, 2) consent rate = number of participants who provide consent\*100 / number of participants who are eligible, 3) enrollment rate = number of participants who are enrolled\*100 / number of participants consented and who complete screening procedures, and 4) loss to follow-up = number of participants who did not complete the end-of-study visit\*100 rate / number of participants randomized.
Safety of the intervention
时间窗: Six months following randomization
To be determined by the number of adverse events, serious adverse events, and unanticipated problems throughout the study, as defined using the standards set forth in the National Cancer Institute's - Common Terminology Criteria (NCI-CTCAE) for AEs version 4.0 and the United States Department of Health and Human Services - Reviewing and Reporting Unanticipated Problems Involving Risks to Subjects or Others and Adverse Events: Office for Human Research Protections Guidance 2007
次要结局
- Timing of the intervention(Immediately following administration of the intervention)
- Proportion of in-person study visits completed(Six months following randomization)
- Common microbial ecology metrics of the maternal vaginal microbiome and of the early-life URT microbiome(At each study time point (birth, ~2 days, ~5 days, ~4 weeks, and ~6 months of age) and over time (longitudinally from birth to age 6 months))
研究者
Christian Rosas-Salazar
Assistant Professor of Pediatrics
Vanderbilt University Medical Center