Pregnancy Complications - A Probiotic Interventional Study

NCT02693041 | Completed

• 1 other identifier: Dnr. 929-11
• Study Type: interventional
• Target: 105
• Locations: 1 country
• Sites: 1

Brief Summary

Investigators hypothesize that a) probiotics decrease the overall inflammatory state in the pregnant woman, especially in women with high risk pregnancies.

Conditions

Preeclampsia; Preterm Birth

Keywords

Probiotics; inflammation; immunological response; preterm birth; preeclampsia

Outcome Measures

Primary Outcomes (3)

• Inflammatory modulation of Lactobacillus Rhamnosus in low risk mothers.

  Intake of LGG Rhamnosus throughout the pregnancy and its effect on levels of subpopulations of lymphocytes in peripheral blood (T/B/NK-celler), and cytokine production (TNF alfa, IL10, IL12) after stimulation with E. Coli, L. paracasei and P. aerugnousa, measuring change from baseline to 25 and 35 weeks gestation.

  at recruitment, week 25, week 35 of gestation

• Inflammatory modulation of Lactobacillus Rhamnosus in mothers with previous preterm birth.

  Intake of LGG Rhamnosus throughout the pregnancy and its effect on levels of subpopulations of lymphocytes in peripheral blood (T/B/NK-celler), and cytokine production (TNF alfa, IL10, IL12) after stimulation with E. Coli, L. paracasei and P. aerugnousa, measuring change from baseline to 25 and 35 weeks gestation.

  at recruitment, week 25, week 35 of gestation

• Inflammatory modulation of Lactobacillus Rhamnosus in mothers with previous preeclampsia.

  Intake of LGG Rhamnosus throughout the pregnancy and its effect on levels of subpopulations of lymphocytes in peripheral blood (T/B/NK-celler), and cytokine production (TNF alfa, IL10, IL12) after stimulation with E. Coli, L. paracasei and P. aerugnousa, measuring change from baseline to 25 and 35 weeks gestation.

  at recruitment, week 25, week 35 of gestation

Study Arms (6)

PROBIOTIC in low-risk women

ACTIVE COMPARATOR

In low-risk women, probiotic group will be treated with the Active ingredient containing Lactobacillus rhamnosus (LGG) (\> 10x8 CFU) during all pregnancy until delivery. Capsules contain maltodextrin, LGG and vegetal magnesium stearate.

Drug: probiotic

PLACEBO in low-risk women

PLACEBO COMPARATOR

In low-risk women, placebo group will be treated with the placebo ingredient during all pregnancy until delivery. The capsules of the placebo Group have similar content but lack the probiotic lactic acid bacteria which has been replaced by maltodextrin to make the mg amount equal.

Drug: placebo

PROBIOTIC in women with a prior PTB

ACTIVE COMPARATOR

In women with a prior preterm birth (PTB), probiotic Group will be treated with the Active ingredient containing Lactobacillus rhamnosus (LGG) (\> 10x8 CFU) during all pregnancy until delivery. Capsules contain maltodextrin, LGG and vegetal magnesium stearate.

Drug: probiotic

PLACEBO in women with a prior PTB

PLACEBO COMPARATOR

In women with a prior preterm birth (PTB), placebo group will be treated with the placebo ingredient during all pregnancy until delivery. The capsules of the placebo Group have similar content but lack the probiotic lactic acid bacteria which has been replaced by maltodextrin to make the mg amount equal.

Drug: placebo

PROBIOTIC in women with a prior PE

ACTIVE COMPARATOR

In women with a prior preeclampsia (PE), probiotic Group will be treated with the Active ingredient containing Lactobacillus rhamnosus (LGG) (\> 10x8 CFU) during all pregnancy until delivery. Capsules contain maltodextrin, LGG and vegetal magnesium stearate.

Drug: probiotic

PLACEBO in women with a prior PE

PLACEBO COMPARATOR

In women with a prior preeclampsia (PE), placebo Group will be treated with the placebo ingredient during all pregnancy until delivery. The capsules of the placebo Group have similar content but lack the probiotic lactic acid bacteria which has been replaced by maltodextrin to make the mg amount equal.

Drug: placebo

Interventions

probiotic DRUG

Low-risk women, women with prior preeclampsia and women with a prior preterm birth will be randomized to be treated with LGG during pregnancy. Effect on maternal and perinatal outcome as well as the effect of treatment on immunological and inflammatory biomarkers will be evaluated.

Also known as: Lactobacillus rhamnosus, LGG

PROBIOTIC in low-risk women; PROBIOTIC in women with a prior PE; PROBIOTIC in women with a prior PTB

placebo DRUG

Low-risk women, women with prior preeclampsia and women with a prior preterm birth will be randomized to be treated with placebo during pregnancy. Effect on maternal and perinatal outcome as well as the effect of treatment on immunological and inflammatory biomarkers will be evaluated.

PLACEBO in low-risk women; PLACEBO in women with a prior PE; PLACEBO in women with a prior PTB

Eligibility Criteria

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

You may qualify if:

• Maternal age \> or = 18 y
• Singleton pregnancy
• Nulli or multiparous without maternal intercurrent diseases or pregnant women with a history of spontaneous preterm delivery or pregnant women with a history of preeclampsia.

You may not qualify if:

• Multiple pregnancy
• Gestational age \> 17+6 weeks at first visit
• Chronic intermittent diseases (e.g. diabetes mellitus, systemic lupus erythematosus, rheumatoid arthritis, Chron disease, ulcerative colitis)
• Uterus malformations
• Immunomodulatory medication
• Hormonal treatment (e.g. crinone, progesterone)
• Subject disagrees to stop intake of other products containing probiotics during study time.
• Subject is unable to provide written informed consent

Sponsors & Collaborators

• Sahlgrenska University Hospital: lead

Study Sites (1)

Bo Jacobsson

Gothenburg, 416 85, Sweden

Location

Related 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.

  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

• 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 RESULT

MeSH Terms

Conditions

Pre-Eclampsia; Premature Birth; Inflammation

Interventions

Probiotics

Condition Hierarchy (Ancestors)

Hypertension, Pregnancy-Induced; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Obstetric Labor, Premature; Obstetric Labor Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms

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: PREVENTION
• 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: June 1, 2012
• Primary Completion: September 27, 2021
• Study Completion: September 27, 2021
• Last Updated: June 3, 2022

Record last verified: 2022-06

Locations

SE (1)