Lactobacillus Reuteri Feasibility Study on Probiotic Treatment and Perinatal Microbiome

Pregnancy Clinical Trial

Official title:

Lactobacillus Reuteri Feasibility Study on Probiotic Lozenges, Probiotic Chewing Gum and Probiotic Capsules and Perinatal Microbiome Seeding During Pregnancy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02693028
• Other study ID #: Dnr. 085-15
• Status: Completed
• Phase: N/A
• Start date: November 2015
• Est. completion date: January 2018

Study information

• Verified date: December 2018
• Source: Sahlgrenska University Hospital, Sweden
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Investigators want to investigate if the Lactobacillus Reuteri (probiotic bacteria) given to pregnant women can be found in different maternal compartments and in the first stool and oral swab collected immediately after birth of a newborn delivered by cesarean delivery. Investigators also want to explore if exposure to this Lactobacillus Reuteri alters the level of inflammation in different compartments of the mother and the infant.

Description:

The purpose of this project is to better understand the following issues:

1. How does bacteria transmit from the mother to the fetus and placenta during pregnancy and to the infant during the first 2-6 weeks after birth?

2. Does colonization of the pregnant mother and fetus/Child occur? How and when?

3. Can orally given probiotic bacteria be found in the newborn 2-6 weeks after birth, and if so where?

4. How is bacteria transported from the mother's intestinal lumen to the Child/fetus gut?

5. What impact has these bacteria on the level of inflammation in maternal and fetal compartments, especially that normally seen in the intestine of all newborns?

6. What impact has these bacteria in the bowel on a normal intestinal flora establishment?

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: January 2018
• Est. primary completion date: January 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Single or multiple gestation

• Maternal age > or = 18 y

Exclusion Criteria:

• Known structural or chromosomal fetal malformation or abnormality

• Occlusive placenta previa, placenta previa in the anterior wall of the uterus, suspicion of accreta/increta/percreta infiltration

• Unable to understand information about the study due to language or severe mental disease

• Known Hepatitis B, C, HIV

• Known immunosuppressive illness if they are under treatment

• Treatment with cytokine, methotrexate or immunosuppresses cytotoxics in the last 6 months before the study.

• Gastro-intestinal surgery including gastric bypass or huge intestinal resection.

• Anaphylactic shock

• Uterus malformation that occludes cervical Canal or uterus segment.

Related Conditions & MeSH terms

• Pregnancy

Intervention

Drug:
• Probiotic lozenges
The women participating in the study will take two probiotic lozenges per day (morning and evening) after meals.Enrollment will be done in gestational week 28-36. The treatment will last for the rest of pregnancy and six weeks post partum.
• Placebo lozenges
The women participating in the study will take two placebo lozenges per day (morning and evening) after meals. Enrollment will be done in gestational week 28-36. The treatment will last for the rest of pregnancy and six weeks post partum.
• Probiotic capsules
The women participating in the study will take two probiotic capsules per day (morning and evening) after meals. Enrollment will be done in gestational week 28-36. The treatment will last for the rest of pregnancy and six weeks post partum.
• Placebo capsules
The women participating in the study will take two placebo capsules per day (morning and evening) after meals. Enrollment will be done in gestational week 28-36. The treatment will last for the rest of pregnancy and six weeks post partum.
• Probiotic chewing gum
The women participating in the study will take two probiotic chewing gums per day (morning and evening) after meals. Enrollment will be done in gestational week 28-36. The treatment will last for the rest of pregnancy and six weeks post partum.

Locations

Country	Name	City	State
Sweden	Sahlgrenska University Hospital	Gothenburg

Sponsors (2)

Lead Sponsor	Collaborator
Sahlgrenska University Hospital, Sweden	BioGaia AB

Country where clinical trial is conducted

Sweden, 

References & Publications (10)

Aagaard K, Ma J, Antony KM, Ganu R, Petrosino J, Versalovic J. The placenta harbors a unique microbiome. Sci Transl Med. 2014 May 21;6(237):237ra65. doi: 10.1126/scitranslmed.3008599. — View Citation

Bertelsen RJ, Brantsæter AL, Magnus MC, Haugen M, Myhre R, Jacobsson B, Longnecker MP, Meltzer HM, London SJ. Probiotic milk consumption in pregnancy and infancy and subsequent childhood allergic diseases. J Allergy Clin Immunol. 2014 Jan;133(1):165-71.e1 — View Citation

Brantsaeter AL, Myhre R, Haugen M, Myking S, Sengpiel V, Magnus P, Jacobsson B, Meltzer HM. Intake of probiotic food and risk of preeclampsia in primiparous women: the Norwegian Mother and Child Cohort Study. Am J Epidemiol. 2011 Oct 1;174(7):807-15. doi: — View Citation

Cobo T, Kacerovsky M, Palacio M, Hornychova H, Hougaard DM, Skogstrand K, Jacobsson B. Intra-amniotic inflammatory response in subgroups of women with preterm prelabor rupture of the membranes. PLoS One. 2012;7(8):e43677. doi: 10.1371/journal.pone.0043677 — View Citation

Gonçalves LF, Chaiworapongsa T, Romero R. Intrauterine infection and prematurity. Ment Retard Dev Disabil Res Rev. 2002;8(1):3-13. Review. — View Citation

Jiménez E, Fernández L, Marín ML, Martín R, Odriozola JM, Nueno-Palop C, Narbad A, Olivares M, Xaus J, Rodríguez JM. Isolation of commensal bacteria from umbilical cord blood of healthy neonates born by cesarean section. Curr Microbiol. 2005 Oct;51(4):270 — View Citation

Jiménez E, Marín ML, Martín R, Odriozola JM, Olivares M, Xaus J, Fernández L, Rodríguez JM. Is meconium from healthy newborns actually sterile? Res Microbiol. 2008 Apr;159(3):187-93. doi: 10.1016/j.resmic.2007.12.007. Epub 2008 Jan 11. — View Citation

Myhre R, Brantsæter AL, Myking S, Gjessing HK, Sengpiel V, Meltzer HM, Haugen M, Jacobsson B. Intake of probiotic food and risk of spontaneous preterm delivery. Am J Clin Nutr. 2011 Jan;93(1):151-7. doi: 10.3945/ajcn.110.004085. Epub 2010 Oct 27. — View Citation

Yeganegi M, Leung CG, Martins A, Kim SO, Reid G, Challis JR, Bocking AD. Lactobacillus rhamnosus GR-1 stimulates colony-stimulating factor 3 (granulocyte) (CSF3) output in placental trophoblast cells in a fetal sex-dependent manner. Biol Reprod. 2011 Jan;84(1):18-25. doi: 10.1095/biolreprod.110.085167. Epub 2010 Sep 1. — View Citation

Yeganegi M, Watson CS, Martins A, Kim SO, Reid G, Challis JR, Bocking AD. Effect of Lactobacillus rhamnosus GR-1 supernatant and fetal sex on lipopolysaccharide-induced cytokine and prostaglandin-regulating enzymes in human placental trophoblast cells: im — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Presence of Lactobacillus reuteri in different compartments in the mother and the Child.	Both cultivation techniques for the specific bacteria and metagenomic techniques will be used to be able to study both cultivable and non-cultivable bacteria.	Mother: From weeks 28-36 of pregnancy until 6 weeks post partum. Child: from birth till 4 years old.
Secondary	Levels of Toll-like receptor stimulated with Lactobacillus plantarum, Pseudomonas aeruginosa and LPS after probiotic treatment and after placebo in different maternal and neonatal compartments.	To evaluate whether there are differences in Toll-like receptor stimulation with Lactobacillus plantarum, Pseudomonas aeruginosa and LPS in different compartments between women treated with probiotic and the placebo group	Mother: From weeks 28-36 of pregnancy until 6 weeks post partum. Child: from birth till 4 years old.
Secondary	Levels of IL-6, IL-10, IL-1beta, MCP-1, IL-17, TNF-alfa after probiotic treatment and after placebo in different maternal and neonatal compartments.	To evaluate whether there are differences in the levels of cytokines and chemokines in different compartments between women treated with probiotic and the placebo group	Mother: From weeks 28-36 of pregnancy until 6 weeks post partum. Child: from birth till 4 years old.