Back to resultsRestoration of Microbiota in Neonates (RoMaNs)
Primary Purpose
Atopic Dermatitis, Atopic Asthma, Immunologic Activity Alteration
Status
Recruiting
Phase
Not Applicable
Locations
Sweden
Study Type
Interventional
Intervention
Maternal microbiota
Sponsored by
About this trial
This is an interventional treatment trial for Atopic Dermatitis focused on measuring microbiota, cesarean section, vaginal delivery, allergy, immunological programming
Eligibility Criteria
Inclusion Criteria:
- Infants of healthy mothers with uncomplicated pregnancies at term, mothers of any ethnic or social background that can speak, read, and understand Swedish to the extent that they can consent in Swedish. An additional inclusion criterion for mothers in the CS groups is vaginal pH ≤ 4 at the time of birth.
Exclusion Criteria:
- Infants of mothers with pre-eclampsia or complicated pregnancies, mothers <18 years or >40 years of age, genital herpes simplex, genital warts, HIV, Hepatitis B or complications during delivery, infants delivered prior to 37 weeks of gestation. Additional exclusion criteria for mothers in the CS group: Mothers positive to Group B Streptococcus, Group A Streptococcus, bacterial vaginosis, vaginal pH > 4 at the time of birth. Mothers with fecal samples positive for Salmonella, Shigella, Campylobacter or Yersinia.
Sites / Locations
- Karolinska InstitutetRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
No Intervention
Active Comparator
Placebo Comparator
Arm Label
vaginally delivered
CS intervention
CS placebo
Arm Description
A non-randomized reference group of vaginally delivered infants.
A piece of gauze soaked with saline (0.9%) will be placed in the birth canal 2 hours before the CS by the study midwife, using sterile glows. Before the CS procedure begins, the gauze will be removed from the vagina and then immediately "contaminated" by a swab carrying maternal fecal microbiota. The swab is contaminated by introducing it 3 cm into the anal canal and by rotating it for 10-20 s. Immediately after birth, the study midwife will swab the neonate with the gauze in multiple body sites by a standardized manner and then swab maternal breasts and chest skin. The neonate will then be placed on the maternal chest to initiate breast-feeding.
See above - the gauze will be exchanged to a clean gauze (soaked with saline). Immediately after birth, the study midwife will swab the neonate with the gauze in multiple body sites by a standardized manner and then swab maternal breasts and chest skin. The neonate will then be placed on the maternal chest to initiate breast-feeding.
Outcomes
Primary Outcome Measures
IgE-associated allergic disease
Incidence of Immunoglubulin E (IgE)-associated allergic disease at 2 years of age in CS delivered infants, compared with non-treated CS-delivered infants and vaginally delivered controls.
Skin-puncture tests will be performed at infant age 6 months, 12 months and child age 24 months.
Secondary Outcome Measures
Immunological programming
Immunological programming will be assessd via blood cell count from blood tests at 6,12 nad 24 months in infants delivered via scheduled CS, with or without exposure to the maternal vaginal and fecal microbiota in comparison to infants born vaginally.
Development of the microbiota
To compare microbial composition between groups, using shotgun metagenomics.
Full Information
NCT ID
NCT03928431
First Posted
April 24, 2019
Last Updated
April 3, 2023
Sponsor
Karolinska Institutet
Collaborators
Uppsala University, Linkoeping University, Umeå University, Örebro University, Sweden, Jonkoping University
1. Study Identification
Unique Protocol Identification Number
NCT03928431
Brief Title
Restoration of Microbiota in Neonates
Acronym
RoMaNs
Official Title
Restoration of Microbiota in Neonates - a Randomized Controlled Trial
Study Type
Interventional
2. Study Status
Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 1, 2019 (Actual)
Primary Completion Date
December 15, 2024 (Anticipated)
Study Completion Date
December 15, 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Karolinska Institutet
Collaborators
Uppsala University, Linkoeping University, Umeå University, Örebro University, Sweden, Jonkoping University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The aim of the study is to examine the effect of exposure of cesarean section (CS) delivered neonates to a natural condition of birth, i.e. to the microbiota of the birth canal, on the acquisition of microbial genes during development of the microbiome at multiple body sites, immune system maturation and allergy risk in childhood
Detailed Description
The primary outcome is to examine if exposure to the maternal vaginal and fecal microbiota directly after birth will halfen the cumulative incidence of Immunoglubulin E (IgE)-associated allergic disease at 2 years of age in CS delivered infants, compared with non-treated CS-delivered infants.
The secondary outcomes are to compare the community structure of microbes from mothers and their infants and immunological programming of infants delivered via scheduled CS, with or without exposure to the maternal vaginal and fecal microbiota, from birth until two years of age. The primary and secondary outcomes will also be compared with a reference group of vaginally delivered infants. Sex differences in the incidence and prevalence of allergic diseases have been described. The anticipated benefit of the intervention can be implemented in clinical practice regardless of sex, so that improved conditions for good health are created.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Atopic Dermatitis, Atopic Asthma, Immunologic Activity Alteration
Keywords
microbiota, cesarean section, vaginal delivery, allergy, immunological programming
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
In this RCT, 330 infants of healthy mothers (age 18 to 40 years) with uncomplicated pregnancies will be included and the infants followed primarily for two years. The number has been increased to cover for potential drop-outs.
Masking
ParticipantInvestigatorOutcomes Assessor
Masking Description
Mothers who give birth by CS will be randomized to expose their neonate to samples of their vaginal and fecal microbiome after birth or to placebo.
Allocation
Randomized
Enrollment
300 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
vaginally delivered
Arm Type
No Intervention
Arm Description
A non-randomized reference group of vaginally delivered infants.
Arm Title
CS intervention
Arm Type
Active Comparator
Arm Description
A piece of gauze soaked with saline (0.9%) will be placed in the birth canal 2 hours before the CS by the study midwife, using sterile glows. Before the CS procedure begins, the gauze will be removed from the vagina and then immediately "contaminated" by a swab carrying maternal fecal microbiota. The swab is contaminated by introducing it 3 cm into the anal canal and by rotating it for 10-20 s.
Immediately after birth, the study midwife will swab the neonate with the gauze in multiple body sites by a standardized manner and then swab maternal breasts and chest skin. The neonate will then be placed on the maternal chest to initiate breast-feeding.
Arm Title
CS placebo
Arm Type
Placebo Comparator
Arm Description
See above - the gauze will be exchanged to a clean gauze (soaked with saline). Immediately after birth, the study midwife will swab the neonate with the gauze in multiple body sites by a standardized manner and then swab maternal breasts and chest skin. The neonate will then be placed on the maternal chest to initiate breast-feeding.
Intervention Type
Other
Intervention Name(s)
Maternal microbiota
Intervention Description
See arm descriptions
Primary Outcome Measure Information:
Title
IgE-associated allergic disease
Description
Incidence of Immunoglubulin E (IgE)-associated allergic disease at 2 years of age in CS delivered infants, compared with non-treated CS-delivered infants and vaginally delivered controls.
Skin-puncture tests will be performed at infant age 6 months, 12 months and child age 24 months.
Time Frame
Two years
Secondary Outcome Measure Information:
Title
Immunological programming
Description
Immunological programming will be assessd via blood cell count from blood tests at 6,12 nad 24 months in infants delivered via scheduled CS, with or without exposure to the maternal vaginal and fecal microbiota in comparison to infants born vaginally.
Time Frame
Two years
Title
Development of the microbiota
Description
To compare microbial composition between groups, using shotgun metagenomics.
Time Frame
Two years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
5 Minutes
Maximum Age & Unit of Time
15 Minutes
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Infants of healthy mothers with uncomplicated pregnancies at term, mothers of any ethnic or social background that can speak, read, and understand Swedish to the extent that they can consent in Swedish. An additional inclusion criterion for mothers in the CS groups is vaginal pH ≤ 4 at the time of birth.
Exclusion Criteria:
Infants of mothers with pre-eclampsia or complicated pregnancies, mothers <18 years or >40 years of age, genital herpes simplex, genital warts, HIV, Hepatitis B or complications during delivery, infants delivered prior to 37 weeks of gestation. Additional exclusion criteria for mothers in the CS group: Mothers positive to Group B Streptococcus, Group A Streptococcus, bacterial vaginosis, vaginal pH > 4 at the time of birth. Mothers with fecal samples positive for Salmonella, Shigella, Campylobacter or Yersinia.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Lars G Engstrand, MD
Phone
+46706780318
Email
lars.engstrand@ki.se
First Name & Middle Initial & Last Name or Official Title & Degree
Marica C Hamsten, MSc
Phone
+46675555872
Email
marica.hamsten@ki.se
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Susanne Nylén, PhD
Organizational Affiliation
Dept Microbiology, Tumour and Cell Biology, Karolinska Institutet, Stockholm
Official's Role
Study Chair
Facility Information:
Facility Name
Karolinska Institutet
City
Stockholm
ZIP/Postal Code
171 65
Country
Sweden
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marica C Hamsten, MSc
Phone
+46765555872
Email
marica.hamsten@k.se
12. IPD Sharing Statement
Plan to Share IPD
Undecided
IPD Sharing Plan Description
Samples will be stored at Karolinska Biobank and metadata will be linked to these samples with access for all researchers in the study. No data will be available for researchers outside the consortium.
Learn more about this trial
Restoration of Microbiota in Neonates
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