Clinical trial NCT05505110: MOdification Of THe Early-Life Respiratory Microbiome Through Vaginal SEEDing
Official title: MOdification Of THe Early-Life Respiratory Microbiome Through Vaginal SEEDing
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: C-section
Vaginal Seeding
Respiratory
Microbiome
Keywords: C-section
Vaginal seeding
Respiratory
Microbiome
Lead sponsor: Vanderbilt University Medical Center
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2022-08-17
Enrollment: 20
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a single-center, parallel-arm, blind, sham-controlled, feasibility RCT to be conducted in healthy cesarean-born children.
Primary purpose: OTHER

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

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

Primary outcomes:
measure: Feasibility of the RCT
timeFrame: Six months following randomization
measure: Safety of the intervention
timeFrame: Six months following randomization
Secondary outcomes:
measure: Timing of the intervention
timeFrame: Immediately following administration of the intervention
measure: Proportion of in-person study visits completed
timeFrame: Six months following randomization
measure: Common microbial ecology metrics of the maternal vaginal microbiome and of the early-life URT microbiome
timeFrame: 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)
Other outcomes:
Locations:
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
Study officials:
affiliation: Vanderbilt University Medical Center
name: Christian Rosas-Salazar, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References: