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

Primary Purpose

Vaginosis, Bacterial

Status
Completed
Phase
Early Phase 1
Locations
Canada
Study Type
Interventional
Intervention
Lactobacillus capsules
Placebo gelatin pill
Sponsored by
Kimberly-Clark Corporation
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Vaginosis, Bacterial

Eligibility Criteria

40 Years - 80 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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.

Sites / Locations

  • Dorli Herman

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Gelatin pill first

Lactobacillus capsules first

Arm Description

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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.
Change in self-reported vaginal symptoms
Symptom analysis to evaluate whether probiotic treatment is associated with symptom relief.

Full Information

First Posted
May 2, 2014
Last Updated
May 13, 2014
Sponsor
Kimberly-Clark Corporation
Collaborators
Lawson Health Research Institute, Western University, Canada, Integrated Research Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT02139839
Brief Title
Exploratory Study to Evaluate the Effects of the Probiotics L. Rhamnosus GR-1 and L. Reuteri RC-14
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2014
Overall Recruitment Status
Completed
Study Start Date
September 2012 (undefined)
Primary Completion Date
March 2013 (Actual)
Study Completion Date
May 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Kimberly-Clark Corporation
Collaborators
Lawson Health Research Institute, Western University, Canada, Integrated Research Inc.

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Vaginosis, Bacterial

7. Study Design

Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
14 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Gelatin pill first
Arm Type
Placebo Comparator
Arm Title
Lactobacillus capsules first
Arm Type
Experimental
Intervention Type
Other
Intervention Name(s)
Lactobacillus capsules
Intervention Description
L. rhamnosus GR-1 and L. reuteri RC-14 capsules manufactured by Chr. Hansen
Intervention Type
Drug
Intervention Name(s)
Placebo gelatin pill
Intervention Description
Placebo Comparator capsules, identical in appearance to the active product; 98% Gelatin with no L. rhamnosus GR-1 and L. reuteri RC- 14.
Primary Outcome Measure Information:
Title
Change from baseline Nugent Score (arbitrary units) after treatment versus Change from baseline Nugent Score after placebo
Description
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.
Time Frame
Baseline Days 15 & 36, post treatment/control Days 19 & 40
Secondary Outcome Measure Information:
Title
Percent Lactobacilli abundance
Description
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.
Time Frame
Untreated (Days 1, 5, & 15), Baseline Treatment I (Days15), Treatment I (Days 19 & 26), Baseline Treatment II (Day 36), Treatment II (Days 40 & 47)
Title
Change in presence of metabolites
Description
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.
Time Frame
Untreated (Days 1, 5, & 15), Baseline Treatment I (Days15), Treatment I (Days 19 & 26), Baseline Treatment II (Day 36), Treatment II (Days 40 & 47)
Title
Change in cytokine/chemokine levels
Description
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.
Time Frame
Untreated (Days 1, 5, & 15), Baseline Treatment I (Days15), Treatment I (Days 19 & 26), Baseline Treatment II (Day 36), Treatment II (Days 40 & 47)
Title
Change in global host gene expression
Description
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.
Time Frame
Untreated (Days 1, 5, & 15), Baseline Treatment I (Days15), Treatment I (Days 19 & 26), Baseline Treatment II (Day 36), Treatment II (Days 40 & 47)
Title
Change in self-reported vaginal symptoms
Description
Symptom analysis to evaluate whether probiotic treatment is associated with symptom relief.
Time Frame
Untreated (Days 1, 5, & 15), Baseline Treatment I (Days15), Treatment I (Days 19 & 26), Baseline Treatment II (Day 36), Treatment II (Days 40 & 47)

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Facility Information:
Facility Name
Dorli Herman
City
London
State/Province
Ontario
ZIP/Postal Code
N6J 0A8
Country
Canada

12. IPD Sharing Statement

Citations:
PubMed Identifier
25127240
Citation
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.
Results Reference
derived

Learn more about this trial

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

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