Effect of Probiotics on GBS Colonization Status During Pregnancy: A Pilot Randomized Controlled Trial

NCT02528981 | Completed

• 1 other identifier: REB 2012-165
• Study Type: interventional
• Target: 114
• Locations: 1 country
• Sites: 1

Brief Summary

Group B Streptococcus (GBS) is the leading cause of neonatal morbidity and mortality in Canada. It may be passed from a study participant colonized in the genital tract by GBS to their baby during vaginal birth. While approximately 10 to 30% of pregnant people harbour GBS in the vagina or rectum, the incidence of neonatal GBS disease is 1 to 2 infants per 1000 births. The use of intrapartum antibiotics to treat colonized individuals with or without risk factors has led to a 70% decline in the incidence of early-onset GBS sepsis in the past decade. Despite this impressive decline, antibiotic resistance has become a major public health concern. Association between intrapartum antibiotic use and ampicillin resistance in E. coli isolated from neonates has previously been documented. Furthermore, while GBS has remained sensitive to penicillin, 20% are resistant to erythromycin and clindamycin, which are alternate drugs for patients allergic to penicillin. Alternative approaches are therefore needed to reduce the risk of GBS infection. We therefore propose to study the use of Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 (Lactobacillus fermentum RC-14) in the colonization status of GBS in pregnant people. Lactobacilli are part of normal gut and vaginal flora and have been widely used as probiotics to treat various conditions. In particular, these two strains have shown to be beneficial in the treatment of urinary tract infections and bacterial vaginosis. Our study design involves recruiting two hundred pregnant people (one hundred in each arm) through various midwifery practices in the GTA at the end of their first trimester of pregnancy. These individuals will be randomized to receive probiotics or placebo for twelve weeks of their pregnancies and will be cultured before delivery to determine their colonization status. The capsules with probiotics and placebo will be provided free of charge. The study design was chosen to minimize the cost and clients' visits to the clinic as vaginal/rectal swabs are routinely offered at 35-37 weeks of gestation.

Conditions

Group B Streptococcal Infection

Keywords

GBS; Probiotics; Group B Streptococcal; Pregnancy

Outcome Measures

Primary Outcomes (1)

• The GBS colonization status of people as determined by a vaginal/rectal swab

  The primary outcome of this study is the GBS colonization status of people as determined by a vaginal/rectal swab, routine to the standard course of midwifery care, taken at 35-37 weeks of pregnancy. Thus, clients are asked to participate in the study for approximately 12 weeks, as per the course of probiotic/placebo. Clients will stop taking the capsules after 12 weeks and once the swab has been performed

  After 12 weeks of taking capsules

Study Arms (2)

Probiotic

EXPERIMENTAL

L. rhamnosus GR-1 and L. reuteri RC-14 will be supplied to 100 randomized pregnant people in gelatin capsules containing 2.5 billion viable cells of each strain (CFU). These organisms have been previously shown to colonize the vagina after being taken orally (11) and displace the pathogens causing bacterial vaginosis (12) and vaginal yeast infections (13), and have been shown to be an effective treatment, or accessory to treatment of these conditions. (7- 9, 13)

Drug: Probiotic

Placebo

PLACEBO COMPARATOR

Placebo capsules will be supplied to 100 randomized pregnant people in gelatin capsules that are identical to the probiotics that the experimental group will receive.

Drug: Placebo

Interventions

Probiotic DRUG

Lactobacillus GR-1 and RC-14

Probiotic

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Pregnant prior to 23 weeks' gestation
• Singleton pregnancy
• Greater than 18 years of age
• Lesser than 45 years of age
• Signed Informed Consent
• Consent to GBS swab that will be offered at the 35-37 week visit
• Consent to chart review at study conclusion

You may not qualify if:

• Multifetal pregnancy
• Fetal complications
• History of preterm birth/second trimester loss
• Significant maternal medical complications
• Unable to provide informed consent
• years of age or lesser than 18 years of age
• years of age or greater than 45 years of age
• HIV positive
• Immuno-compromised E.g.: Persons with AIDS; cancer and transplant patients who are taking certain immunosuppressive drugs; and those with inherited diseases that affect the immune system (e.g., congenital agammaglobulinemia, congenital IgA deficiency).
• History of previous child affected by Early Onset GBS Disease (EOGBSD)
• GBS bacteruria in pregnancy
• Antibiotic treatment required during study period
• Enrolled in other research with a drug
• Taking another probiotic supplement

Sponsors & Collaborators

• Toronto Metropolitan University: lead
• Chr Hansen: collaborator

Study Sites (1)

Ryerson University

Toronto, Ontario, Canada

Location

Related Publications (15)

• Stoll BJ, Hansen NI, Sanchez PJ, Faix RG, Poindexter BB, Van Meurs KP, Bizzarro MJ, Goldberg RN, Frantz ID 3rd, Hale EC, Shankaran S, Kennedy K, Carlo WA, Watterberg KL, Bell EF, Walsh MC, Schibler K, Laptook AR, Shane AL, Schrag SJ, Das A, Higgins RD; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Early onset neonatal sepsis: the burden of group B Streptococcal and E. coli disease continues. Pediatrics. 2011 May;127(5):817-26. doi: 10.1542/peds.2010-2217. Epub 2011 Apr 25.

  PMID: 21518717 BACKGROUND

• Verani JR, McGee L, Schrag SJ; Division of Bacterial Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention (CDC). Prevention of perinatal group B streptococcal disease--revised guidelines from CDC, 2010. MMWR Recomm Rep. 2010 Nov 19;59(RR-10):1-36.

  PMID: 21088663 BACKGROUND

• Darling E, Saurette K. Clinical Practice Guideline No.11: Group B Streptococcus: Prevention and Management in Labour. Toronto: Association of Ontario Midwives 2010.

  BACKGROUND

• Money DM, Dobson S; Canadian Paediatric Society, Infectious Diseases Commitee. RETIRED: The prevention of early-onset neonatal group B streptococcal disease. J Obstet Gynaecol Can. 2004 Sep;26(9):826-40. doi: 10.1016/s1701-2163(16)30157-8. English, French.

  PMID: 15361281 BACKGROUND

• Kalliomaki M, Salminen S, Isolauri E. Positive interactions with the microbiota: probiotics. Adv Exp Med Biol. 2008;635:57-66. doi: 10.1007/978-0-387-09550-9_5.

  PMID: 18841703 BACKGROUND

• Reid G, Dols J, Miller W. Targeting the vaginal microbiota with probiotics as a means to counteract infections. Curr Opin Clin Nutr Metab Care. 2009 Nov;12(6):583-7. doi: 10.1097/MCO.0b013e328331b611.

  PMID: 19741517 BACKGROUND

• Anukam K, Osazuwa E, Ahonkhai I, Ngwu M, Osemene G, Bruce AW, Reid G. Augmentation of antimicrobial metronidazole therapy of bacterial vaginosis with oral probiotic Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14: randomized, double-blind, placebo controlled trial. Microbes Infect. 2006 May;8(6):1450-4. doi: 10.1016/j.micinf.2006.01.003. Epub 2006 Mar 29.

  PMID: 16697231 BACKGROUND

• Martinez RC, Franceschini SA, Patta MC, Quintana SM, Gomes BC, De Martinis EC, Reid G. Improved cure of bacterial vaginosis with single dose of tinidazole (2 g), Lactobacillus rhamnosus GR-1, and Lactobacillus reuteri RC-14: a randomized, double-blind, placebo-controlled trial. Can J Microbiol. 2009 Feb;55(2):133-8. doi: 10.1139/w08-102.

  PMID: 19295645 BACKGROUND

• Martinez RC, Franceschini SA, Patta MC, Quintana SM, Candido RC, Ferreira JC, De Martinis EC, Reid G. Improved treatment of vulvovaginal candidiasis with fluconazole plus probiotic Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14. Lett Appl Microbiol. 2009 Mar;48(3):269-74. doi: 10.1111/j.1472-765X.2008.02477.x. Epub 2009 Feb 2.

  PMID: 19187507 BACKGROUND

• Reid G, Kirjaivanen P. Taking probiotics during pregnancy. Are they useful therapy for mothers and newborns? Can Fam Physician. 2005 Nov;51(11):1477-9.

  PMID: 16353828 BACKGROUND

• Morelli L, Zonenenschain D, Del Piano M, Cognein P. Utilization of the intestinal tract as a delivery system for urogenital probiotics. J Clin Gastroenterol. 2004 Jul;38(6 Suppl):S107-10. doi: 10.1097/01.mcg.0000128938.32835.98.

  PMID: 15220672 BACKGROUND

• Burton JP, Cadieux PA, Reid G. Improved understanding of the bacterial vaginal microbiota of women before and after probiotic instillation. Appl Environ Microbiol. 2003 Jan;69(1):97-101. doi: 10.1128/AEM.69.1.97-101.2003.

  PMID: 12513982 BACKGROUND

• Reid G, Beuerman D, Heinemann C, Bruce AW. Probiotic Lactobacillus dose required to restore and maintain a normal vaginal flora. FEMS Immunol Med Microbiol. 2001 Dec;32(1):37-41. doi: 10.1111/j.1574-695X.2001.tb00531.x.

  PMID: 11750220 BACKGROUND

• Bocking A. Probiotic therapy for the reversal of Bacterial Vaginosis in pregnancy (ProVIP). ClinicalTrials.gov [Internet]. Accessed January 2013. Available from: http://www.clinicaltrials.gov/ct2/show/NCT01697683?term=Bocking%2C+A&rank=10

  BACKGROUND

• Reid G. Effects of probiotics on rheumatoid arthritis patients. ClinicalTrials.gov [Internet]. Accessed January 2013. Available from: http://www.clinicaltrials.gov/ct2/show/NCT00664820?term=%22Canada%22+AND+%22Probiotics%22&rank=2

  BACKGROUND

MeSH Terms

Conditions

Streptococcal Infections

Interventions

Probiotics

Condition Hierarchy (Ancestors)

Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

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

Study Officials

• Mary Sharpe, PhD

  Toronto Metropolitan University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: August 18, 2015
• First Posted: August 19, 2015
• Study Start: August 1, 2015
• Primary Completion: June 1, 2016
• Study Completion: July 1, 2016
• Last Updated: March 7, 2017

Record last verified: 2017-03

Locations

CA (1)