Exploratory Study to Evaluate the Effects of the Probiotics L. Rhamnosus GR-1 and L. Reuteri RC-14

A Single-Center Exploratory Study to Evaluate the Effects of the Probiotics L. Rhamnosus GR-1 and L. Reuteri RC-14 on Subjects With Intermediate Nugent Scores

The purpose of this study was to determine whether L. rhamnosus GR-1 and L. reuteri RC-14 delivered via capsules to the vagina of post-menopausal women over a three day course of treatment can restore and maintain a lactobacilli-dominated microbiota. Exploratory analysis of microbial ecology, human microarrays and multiplex immunological assessments are included to characterize potential effects.

Study Overview

• Status: Completed
• Conditions: Vaginosis, Bacterial
• Intervention / Treatment: Other: Lactobacillus capsules; Drug: Placebo gelatin pill

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • London, Ontario, Canada, N6J 0A8
      • Dorli Herman

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Willing and able to read, understand, and sign the Informed Consent Form (ICF);
• Post-menopausal females between the ages of 40 and 80 years old (subjects who have not had a menstrual period for the last 12 months);
• Currently in a mutually monogamous sexual relationship or not sexually active;
• Agree to be sexually abstinent 72 hours prior to each study visit. Also, agree to refrain from intercourse for 48 hours after treatment administration;
• Agree to abstain from the use of any other intravaginal product (e.g. gels, foams, lubricants, douches, etc.) throughout the study period, from the time of screening until Day 47;
• Willing and capable of following all study instructions; and
• Good general health.

Exclusion Criteria:

• Use of vaginal lubricants, or any products applied vaginally within three months prior to Visit 1and throughout the duration of study participation;
• A history or currently undergoing immunosuppressive drug therapy, chemotherapy, or radiation therapy;
• A medical condition which might compromise immune system functions (such as cancer, leucopenia, HIV-positive, or organ transplant);
• Antibiotics and/or antifungal medication use within the last four (4) weeks;
• Oral probiotic supplement use within 3 months prior to Visit 1 and throughout the duration of the study;
• Significant changes in diet during the course of the study based on self-report;
• Induced menopause due to surgical or medical interventions, such as bilateral oophorectomy, hysterectomy, chemotherapy or radiation treatment;
• Currently undergoing local or systemic estrogen therapy who are not willing to alter therapy during the course of the study;
• A Nugent Score of 0 - 3 or greater than 6;
• History of drug or alcohol abuse;
• Currently diagnosed with or being treated for a genital infection or urinary tract infection;
• Individuals with a sexually transmitted disease (self-reported or detected by the Principal Investigator);
• At enrollment, have any social or medical condition, or psychiatric illness that, in the opinion of the Investigator, would preclude provision of informed consent, make participation in the study unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives;
• Participation in a clinical trial involving an investigational product/device within the past three months; subjects who are scheduled to participate in another clinical study concurrently; and
• Known intolerance or allergy to L. rhamnosus GR-1® or L. reuteri RC-14® or to any product excipients.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Gelatin pill first	Other: Lactobacillus capsules; L. rhamnosus GR-1 and L. reuteri RC-14 capsules manufactured by Chr. Hansen; Drug: Placebo gelatin pill; Placebo Comparator capsules, identical in appearance to the active product; 98% Gelatin with no L. rhamnosus GR-1 and L. reuteri RC- 14.
Experimental: Lactobacillus capsules first	Other: Lactobacillus capsules; L. rhamnosus GR-1 and L. reuteri RC-14 capsules manufactured by Chr. Hansen; Drug: Placebo gelatin pill; Placebo Comparator capsules, identical in appearance to the active product; 98% Gelatin with no L. rhamnosus GR-1 and L. reuteri RC- 14.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline Nugent Score (arbitrary units) after treatment versus Change from baseline Nugent Score after placebo	Determine whether L. rhamnosus GR-1 and L. reuteri RC-14 delivered via capsules to the vagina of post-menopausal women over a three day course of treatment can restore and maintain a lactobacilli-dominated microbiota for one week as measured by a decrease in the Nugent Scores from an intermediate score (4 - 6) at baseline to a normal score (0 - 3) following treatment compared to a placebo.	Baseline Days 15 & 36, post treatment/control Days 19 & 40

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Lactobacilli abundance	Change in lactobacilli abundance before and after probiotic treatment and before and after placebo treatment. Lactobacilli abundance will be calculated as percentage of number of lactobacilli taxon divided by the total number of taxons.	Untreated (Days 1, 5, & 15), Baseline Treatment I (Days15), Treatment I (Days 19 & 26), Baseline Treatment II (Day 36), Treatment II (Days 40 & 47)
Change in presence of metabolites	Gas chromatography-mass spectrometry will be used to determine changes in metabolites (such as lactate, glutamic acid, and others) before and after probiotic and placebo treatments.	Untreated (Days 1, 5, & 15), Baseline Treatment I (Days15), Treatment I (Days 19 & 26), Baseline Treatment II (Day 36), Treatment II (Days 40 & 47)
Change in cytokine/chemokine levels	Multiplex ELISA based assay will be used to evaluate the modulation of cytokine and chemokine levels known regulate inflammation and host defense response before and after probiotic and placebo treatment.	Untreated (Days 1, 5, & 15), Baseline Treatment I (Days15), Treatment I (Days 19 & 26), Baseline Treatment II (Day 36), Treatment II (Days 40 & 47)
Change in global host gene expression	Microarray analysis using GeneChip Human 2.0 ST array will be used to measure gene expression changes (by mRNA analysis) to determine whether there are differences in gene regulation between probiotic, placebo, and no treatment conditions.	Untreated (Days 1, 5, & 15), Baseline Treatment I (Days15), Treatment I (Days 19 & 26), Baseline Treatment II (Day 36), Treatment II (Days 40 & 47)
Change in self-reported vaginal symptoms	Symptom analysis to evaluate whether probiotic treatment is associated with symptom relief.	Untreated (Days 1, 5, & 15), Baseline Treatment I (Days15), Treatment I (Days 19 & 26), Baseline Treatment II (Day 36), Treatment II (Days 40 & 47)

Collaborators and Investigators

• Sponsor: Kimberly-Clark Corporation
• Collaborators: Lawson Health Research Institute; Western University, Canada; Integrated Research Inc.

Publications and helpful links

General Publications

• Bisanz JE, Seney S, McMillan A, Vongsa R, Koenig D, Wong L, Dvoracek B, Gloor GB, Sumarah M, Ford B, Herman D, Burton JP, Reid G. A systems biology approach investigating the effect of probiotics on the vaginal microbiome and host responses in a double blind, placebo-controlled clinical trial of post-menopausal women. PLoS One. 2014 Aug 15;9(8):e104511. doi: 10.1371/journal.pone.0104511. eCollection 2014.

Study record dates

Study Major Dates

• Study Start: September 1, 2012
• Primary Completion (Actual): March 1, 2013
• Study Completion (Actual): May 1, 2013

Study Registration Dates

• First Submitted: May 2, 2014
• First Submitted That Met QC Criteria: May 13, 2014
• First Posted (Estimate): May 15, 2014

Study Record Updates

• Last Update Posted (Estimate): May 15, 2014
• Last Update Submitted That Met QC Criteria: May 13, 2014
• Last Verified: May 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Vaginal Diseases; Vaginitis; Vaginosis, Bacterial
• Other Study ID Numbers: 500-10-0002

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No