Lactobacillus Reuteri Feasibility Study on Probiotic Treatment and Perinatal Microbiome

NCT02693028 | Completed

• 1 other identifier: Dnr. 085-15
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Pregnancy

Keywords

Microbiome; probiotic

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• 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.

  Mother: From weeks 28-36 of pregnancy until 6 weeks post partum. Child: from birth till 4 years old.

• 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.

  Mother: From weeks 28-36 of pregnancy until 6 weeks post partum. Child: from birth till 4 years old.

Study Arms (5)

probiotic lozenge

ACTIVE COMPARATOR

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.

Drug: Probiotic lozenges

Probiotic capsule

ACTIVE COMPARATOR

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.

Drug: Probiotic capsules

Probiotic chewing gum

ACTIVE COMPARATOR

The probiotic chewing gum should be chewed on for about 10 minutes. Enrollment will be done in gestational week 28-36. The treatment will last for the rest of pregnancy and six weeks post partum.

Drug: Probiotic chewing gum

Placebo lozenge

PLACEBO COMPARATOR

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.

Drug: Placebo lozenges

Placebo capsule

PLACEBO COMPARATOR

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.

Drug: Placebo capsules

Interventions

Probiotic lozenges DRUG

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.

Also known as: Lactobacillus reuteri lozenges

probiotic lozenge

Placebo lozenges DRUG

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.

Also known as: "non active" treatment lozenges

Placebo lozenge

Probiotic capsules DRUG

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.

Also known as: Lactobacillus reuteri capsules

Probiotic capsule

Placebo capsules DRUG

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.

Also known as: "non active" treatment capsules

Placebo capsule

Probiotic chewing gum DRUG

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.

Also known as: Lactobacillus reuteri chewing gum

Probiotic chewing gum

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Single or multiple gestation
• Maternal age \> or = 18 y

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sahlgrenska University Hospital: lead
• BioGaia AB: collaborator

Study Sites (1)

Sahlgrenska University Hospital

Gothenburg, Sweden

Location

Related Publications (10)

• 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.

  PMID: 20811016 BACKGROUND

• 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.

  PMID: 24848255 RESULT

• 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. Epub 2012 Aug 20.

  PMID: 22916296 RESULT

• Goncalves LF, Chaiworapongsa T, Romero R. Intrauterine infection and prematurity. Ment Retard Dev Disabil Res Rev. 2002;8(1):3-13. doi: 10.1002/mrdd.10008.

  PMID: 11921380 RESULT

• Jimenez E, Fernandez L, Marin ML, Martin R, Odriozola JM, Nueno-Palop C, Narbad A, Olivares M, Xaus J, Rodriguez JM. Isolation of commensal bacteria from umbilical cord blood of healthy neonates born by cesarean section. Curr Microbiol. 2005 Oct;51(4):270-4. doi: 10.1007/s00284-005-0020-3. Epub 2005 Sep 20.

  PMID: 16187156 RESULT

• Jimenez E, Marin ML, Martin R, Odriozola JM, Olivares M, Xaus J, Fernandez L, Rodriguez 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.

  PMID: 18281199 RESULT

• Myhre R, Brantsaeter 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.

  PMID: 20980489 RESULT

• 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: 10.1093/aje/kwr168. Epub 2011 Aug 5.

  PMID: 21821542 RESULT

• Bertelsen RJ, Brantsaeter 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.e1-8. doi: 10.1016/j.jaci.2013.07.032. Epub 2013 Sep 10.

  PMID: 24034345 RESULT

• 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: implications for treatment of bacterial vaginosis and prevention of preterm labor. Am J Obstet Gynecol. 2009 May;200(5):532.e1-8. doi: 10.1016/j.ajog.2008.12.032. Epub 2009 Mar 14.

  PMID: 19285652 RESULT

MeSH Terms

Interventions

Probiotics

Intervention Hierarchy (Ancestors)

Dietary Supplements; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages

Study Officials

• Bo Jacobsson, Professor

  Göteborg University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical professor

Study Record Dates

• First Submitted: October 12, 2015
• First Posted: February 26, 2016
• Study Start: November 1, 2015
• Primary Completion: January 1, 2018
• Study Completion: January 1, 2018
• Last Updated: December 12, 2018

Record last verified: 2018-12

Locations

SE (1)