Probiotic Therapy for the Reversal of Bacterial Vaginosis in Pregnancy (ProVIP)

This study will add to the current knowledge and literature on the ability of an oral lactobacilli preparation to return the vaginal flora to a normal state in pregnant women. The results will potentially serve as the basis for a multi-centre Phase III randomized clinical trial to determine the efficacy of this treatment in preventing preterm birth.

Study Overview

• Status: Completed
• Conditions: Pregnant Women Who Test Positive for Bacterial Vaginosis
• Intervention / Treatment: Drug: Placebo; Drug: Probiotic Lactobacilli

Detailed Description

Preterm birth continues to provide the greatest challenge in perinatal health care in the developed world. It is a syndrome involving multiple causes and arises from a number of social, psychological, and biological determinants. It has been estimated that intrauterine infection accounts for at least 25-40% of spontaneous preterm births, with infection being the primary cause of extreme prematurity. Because infection-mediated preterm delivery mainly occurs in younger gestational ages (less than 28 weeks), these extremely premature babies not only have the risks associated with being born early, but are also likely to have severe morbidities associated with infection. Bacterial vaginosis (BV) is defined as a loss or significant depletion of lactobacilli coupled with an overgrowth of pathogenic bacteria and an increase in vaginal pH (>4.5). BV is common and occurs in 20% of the general female population, often without symptoms and is associated with a 40% increased risk of preterm birth. The clinical finding that lactobacilli is the dominant microbe in the vagina of women with a healthy pregnancy and full term delivery, supports the association of this species with a healthy pregnancy. BV is associated with an elevation of cervico-vaginal pro-inflammatory cytokines including IL-1β and IL-8 that are also associated with preterm labour; initiating the inflammatory cascade of events involved in labour may be the mechanism by which BV triggers preterm birth. However, not all women with BV will deliver preterm suggesting that variations in genetic susceptibility may underlie the host response to the presence of BV and the risk for preterm birth. Antibiotic therapy is the current treatment for BV, but the extent to which antibiotics can prevent preterm birth in women with BV remains somewhat uncertain, with conflicting results published in the literature. The apparent ineffective nature of antibiotic therapy, perhaps due to a lack of regrowth of lactobacilli following treatment, and the possibility that the pathogens have already induced inflammatory processes that will eventually induce preterm birth, emphasizes the need to continue to investigate the role of microbes during pregnancy. Probiotics have been suggested as an alternative to antibiotic therapy in restoring vaginal lactobacilli and reversing BV. The study seeks to determine whether Lactobacillus rhamnosus, GR-1 and Lactobacillus reuteri, RC-14 when administered to pregnant women diagnosed with bacterial vaginosis or intermediate flora will reverse the condition leading to a decrease in the inflammatory mediators involved in the cascade of infection/inflammation-mediated preterm birth.

• Study Type: Interventional
• Enrollment (Actual): 86
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X5
      • Mount Sinai Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• pregnant women prior to 17 weeks gestation
• singleton pregnancy
• over 18 years of age
• able to provide informed consent

Exclusion Criteria:

• multifetal pregnancies (twins, triplets, etc)
• fetal complications (congenital anomaly, chromosomal abnormality)
• maternal history of previous preterm birth or second trimester loss
• significant maternal medical or surgical complications (eg. hypertension, diabetes)
• less than 18 years of age
• unable to provide informed consent
• HIV Positive
• Immuno-compromised

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Sugar pill	Drug: Placebo
Active Comparator: Probiotic Rhamnosus Lactobacilli	Drug: Probiotic Lactobacilli; Two capsules per day containing either probiotic lactobacilli or placebo for 12 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Microbial DNA profile	A change in the Vaginal Microbial DNA profile	At 28 and at 35 weeks gestation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Microbial function	A change in microbial function as measured by RNA transcriptomics	At 28 and at 35 weeks gestation

Collaborators and Investigators

• Sponsor: Mount Sinai Hospital, Canada
• Collaborators: Unity Health Toronto
• Investigators: Principal Investigator: Alan Bocking, MD, Mount Sinai Hospital

Study record dates

Study Major Dates

• Study Start: May 1, 2012
• Primary Completion (Actual): March 1, 2014
• Study Completion (Actual): March 1, 2014

Study Registration Dates

• First Submitted: September 28, 2012
• First Submitted That Met QC Criteria: October 1, 2012
• First Posted (Estimate): October 2, 2012

Study Record Updates

• Last Update Posted (Estimate): March 24, 2014
• Last Update Submitted That Met QC Criteria: March 20, 2014
• Last Verified: March 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Vaginitis; Vaginal Diseases; Vaginosis, Bacterial
• Other Study ID Numbers: 08-0005-A