Clinical trial NCT02139839: 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
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Vaginosis, Bacterial
Lead sponsor: Kimberly-Clark Corporation
Sponsor class: INDUSTRY
Collaborators: name: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
name: Western University, Canada
name: Integrated Research Inc.
First posted: 2014-05-15
Enrollment: 14
Sex: FEMALE
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Change from baseline Nugent Score (arbitrary units) after treatment versus Change from baseline Nugent Score after placebo
timeFrame: Baseline Days 15 & 36, post treatment/control Days 19 & 40
Secondary outcomes:
measure: Percent Lactobacilli abundance
timeFrame: Untreated (Days 1, 5, & 15), Baseline Treatment I (Days15), Treatment I (Days 19 & 26), Baseline Treatment II (Day 36), Treatment II (Days 40 & 47)
measure: Change in presence of metabolites
timeFrame: Untreated (Days 1, 5, & 15), Baseline Treatment I (Days15), Treatment I (Days 19 & 26), Baseline Treatment II (Day 36), Treatment II (Days 40 & 47)
measure: Change in cytokine/chemokine levels
timeFrame: Untreated (Days 1, 5, & 15), Baseline Treatment I (Days15), Treatment I (Days 19 & 26), Baseline Treatment II (Day 36), Treatment II (Days 40 & 47)
measure: Change in global host gene expression
timeFrame: Untreated (Days 1, 5, & 15), Baseline Treatment I (Days15), Treatment I (Days 19 & 26), Baseline Treatment II (Day 36), Treatment II (Days 40 & 47)
measure: Change in self-reported vaginal symptoms
timeFrame: Untreated (Days 1, 5, & 15), Baseline Treatment I (Days15), Treatment I (Days 19 & 26), Baseline Treatment II (Day 36), Treatment II (Days 40 & 47)
Other outcomes:
Locations:
city: London
country: Canada
facility: Dorli Herman
state: Ontario
Study officials:
References:
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.