Intestinal Microbiota Composition After Antibiotic Treatment in Early Life

Eczema Clinical Trial

— INCA  

Official title:

"Intestinal Microbiota Composition After Antibiotic Treatment in Early Life. The INCA Study"

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02536560
• Other study ID #: NL.37233.100.11, R-11.26AM
• Status: Recruiting
• Phase: N/A
• First received: August 21, 2015
• Last updated: August 28, 2015
• Start date: January 2012
• Est. completion date: October 2016

Study information

• Verified date: August 2015
• Source: Agentschap NL
• Contact: Nicole B Rutten, MD
• Phone: +31 88 320 6325
• Email: n.rutten[@]antoniusziekenhuis.nl
• Is FDA regulated: No
• Health authority: Netherlands: Medical Ethics Review Committee (METC)
• Study type: Observational

Clinical Trial Summary

In this prospective observational cohort study the potential clinical consequences of antibiotic use in early life and perturbations in the gastrointestinal microbiota composition due to that antibiotic use are studied. It is hypothesized that altered microbiota may be an important underlying mechanism for impediments in the developing immune system.

Differentiation will be made between a group of neonates who received antibiotics in the first week of life, and control infants who were not exposed to antibiotics in the neonatal period.

Description:

Healthy newborns born in the hospital, observed for low probability of neonatal infection will be compared to newborns exposed to antibiotic therapy in early life (first 1-2 weeks).

Infants are recruited from the maternity wards and neonatal wards of four teaching hospitals in the Netherlands. In total 150 infants, treated with antibiotics because of (a high suspicion of) a perinatal infection during the first week of life, will be recruited. The control group comprises 300 healthy newborns, born in the hospital and needing clinical observation for 24-48 hours for several reasons like maternal comorbidity, low probability of neonatal infection, blood sugar monitoring, meconium containing amniotic fluid, or delivery by caesarean section.

Differences in clinical outcomes between antibiotic treated infants and controls are investigated. Incidence of atopic dermatitis (eczema), food allergy, upper respiratory tract infections (URTI), lower respiratory tract infections (LRTI), gastrointestinal infections (GITI) and excessive crying are evaluated, prospectively assessed by parental reports and retrospectively assessed by doctor's diagnoses. The clinical endpoints will be linked to the developing intestinal microbiota during the first year of life.

Potential differences in intestinal fecal microbiota composition and diversity can be determined at eight time points during the first year of life, as sampling moments include: day one (T1), day two (T2), one week (T3), two weeks (T4), one month (T5), three months (T6), six months (T7), one year (T8).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 450
• Est. completion date: October 2016
• Est. primary completion date: April 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: N/A to 7 Days

Eligibility

Inclusion Criteria:

1. Term-born babies (= 36 weeks gestational age)

2. (Short) stay on maternal ward or admission to neonatal ward because of antibiotic treatment

3. Signed informed consent by the parents

Exclusion Criteria:

1. Congenital illness or malformations

2. Severe perinatal infections for which transfer to the neonatal intensive care unit is needed

3. Maternal probiotic use = six weeks before delivery

4. Insufficient knowledge of the Dutch language.

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Atopy
• Eczema
• Microbiota

Locations

Country	Name	City	State
Netherlands	Meander Medical Centre	Amersfoort	Utrecht
Netherlands	Gelre Hospitals	Apeldoorn	Gelderland
Netherlands	Tergooi Hospital	Blaricum	Utrecht
Netherlands	St Antonius Hospital	Nieuwegein	Utrecht

Sponsors (3)

Lead Sponsor	Collaborator
Agentschap NL	Danone Research, VU University Medical Center

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	infant height	Individual height is monitored during the first year of life. Parents report the most recently measured height of the child on the calendar lists.; (height is measured in centimeters)	Participant's height is monitored during the first year of life	No
Other	infant weight	Individual weight is monitored during the first year of life. Parents report the most recently measured weight of the child on the calendar lists.; (weight is measured in kilograms)	Participant's weight is monitored during the first year of life	No
Other	coughing	Parental reported symptom on calendar list (yes/no). Description: The child coughs several times a day and/or has coughing. Regularly there are signs of cold. Cough because of choking does not have to be recorded.	the symptom is daily reported as present or not present (by the parents, on the calendar list), during the infant's first year of life	No
Other	wheezing	Parental reported symptom on calendar list (yes/no). Description: During expiration the parents notice a whistling, wheezy sound coming from the lower airways of the child. During expiration the child is trying to squeeze the air outwards. Wheezing coming from or through the nose does not have to be recorded.	the symptom is daily reported as present or not present (by the parents, on the calendar list), during the infant's first year of life	No
Other	fever >38 degrees Celsius	Parental reported symptom on calendar list (yes/no). Description: Clear from itself, whereby it is important that parents use a rectal thermometer, measure twice and the temperature is >38 degrees Celsius on both occasions.	the symptom is daily reported as present or not present (by the parents, on the calendar list), during the infant's first year of life	No
Other	runny nose	Parental reported symptom on calendar list (yes/no). Description: Signs of cold with white/yellow/green mucus running from the nose.	the symptom is daily reported as present or not present (by the parents, on the calendar list), during the infant's first year of life	No
Other	glue ear	Parental reported symptom on calendar list (yes/no). Description: The child seems to have earache and/or grasps its ear (the ear frequently is high-colored or bends) and/or glue egresses from the ear.	the symptom is daily reported as present or not present (by the parents, on the calendar list), during the infant's first year of life	No
Other	rash	Parental reported symptom on calendar list (yes/no). Description: More than one day existing skin-redness (spots, rash, pimples) on the face, arms or legs, trunk. Disease-symptoms are not necessarily present. The rash can be eczema; eczema mostly is red, scaly and may itch. Infants cheeks are affected mostly. When children grow up, elbow and knees are preferred sites.	the symptom is daily reported as present or not present (by the parents, on the calendar list), during the infant's first year of life	No
Other	diarrhea	Parental reported symptom on calendar list (yes/no). Description: Watery or mucous defecation, more than three times a day, that continues more than one day.	the symptom is daily reported as present or not present (by the parents, on the calendar list), during the infant's first year of life	No
Other	>3 crying hours a day	Parental reported symptom on calendar list (yes/no). Description: Clear from itself, whereby the total crying episodes add up to more than three hours a day (24 hours) in total.	the symptom is daily reported as present or not present (by the parents, on the calendar list), during the infant's first year of life	No
Other	prescribed antibiotics	Any prescribed (systemic) antibiotic treatments during the first year of life are investigated. Measured as number of antibiotic courses during the first year of life, [1] parental reported (on the calendar list) and [2] checked via pharmacist's medication records.	Participants will be followed during their first year of life and prescription of antibiotic courses will be monitored	No
Other	allergic sensitization	(serum) allergen antibodies to food and inhalant allergens are determined. Measured in kilo unit.	around 1 year of age	No
Primary	Clinical endpoints	Differences in clinical outcomes between antibiotic treated infants and controls are investigated. Incidence of atopic dermatitis (eczema), food allergy, upper respiratory tract infections (URTI), lower respiratory tract infections (LRTI), gastrointestinal infections (GITI) and excessive crying are evaluated. Data are prospectively assessed by parental reports (calendar lists).	Participants will be followed during their first year of life	No
Secondary	Microbiota composition	Fecal bacterial composition and diversity is determined at eight time points during the first year of life, from birth on. Sampling points include: day one (T1), day two (T2), one week (T3), two weeks (T4), one month (T5), three months (T6), six months (T7), one year (T8).; Potential differences in microbiota composition and diversity will be determined by use of 16S-23S ribosomal ribonucleic acid (rRNA) gene analysis (IS-pro).	Samples will be taken at eight time points during the participant's first year of life	No
Secondary	Vaccine response	Immunoglobulin G antibodies against Tetanus toxoid, Diphtheria toxoid, Haemophilus influenza type B, and the capsular polysaccharides of the pneumococcal 10-valent conjugate vaccine will be determined.; Antibody concentrations will be determined from blood samples. Measured in international units per milliliter or microgram per milliliter.	around 1 year of age	No
Secondary	Doctor's diagnosis	Diagnoses are defined by selected International Classification system of Primary Care (ICPC) codes, diagnosticated during the first year of life.; These include: dyspnea (R02), wheezing (R03), cough (R05), acute upper tract infection (R74), acute bronchi(oli)tis (R78), pneumonia (R81), asthma like symptoms (R96), breath problems [R04], sneeze [R07], other symptoms of the nose [R08], symptoms of the throat [R21], abnormal sputum [R25], concern about respiratory illness [R27], acute laryngitis [R77], influenza [R88], other infections of the airways [R83], and other respiratory diseases [R99], infectious diarrhea (D70), vomiting (D10), susceptible gastro-intestinal infection (D73), other symptoms/complaints of the skin (S21), dry skin/ flaking (S21.01), infantile colic (A14).	Participants will be followed during their first year of life	No