Vaginal Probiotics and Pessaries and Their Impact on the Vaginal Microenvironment

The Effect of Vaginal Probiotics on the Vaginal Microenvironment in Patients Using Vaginal Pessaries: a Randomized Controlled Trial.

In this study, the investigators are evaluating the effect of vaginal probiotics on the bothersome side effects of pessary use and the impact on the vaginal microenvironment (lactobacilli, anaerobic bacteria, mobiluncus bacteria, WBCs, cellular debris, epithelial cells, and BVAB-1), and inflammatory environment (cytokines).

Study Overview

• Status: Completed
• Conditions: Inflammatory Response; Pelvic Organ Prolapse; Dysbiosis
• Intervention / Treatment: Other: BiopHreshTM vaginal probiotic supplement (Good Clean Love, Inc. Eugene, OR) and RestoreTM gel.; Other: Standard Care

• Study Type: Interventional
• Enrollment (Actual): 141
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • Hartford, Connecticut, United States, 06103
      • Hartford Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 89 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Postmenopausal (no menstruation >12 months)
• Subjects presenting for 2 week post initial pessary insertion appointment or presenting for routine pessary care follow up appointment
• Planning on continuing to use a pessary for treatment for at least 3 months
• Pessary maintenance performed by provider (as opposed to self-care)
• Able to understand English
• Able/willing to sign informed consent document

Exclusion Criteria:

• Lack of cognitive ability to consent to participate in study and to complete the questionnaires
• Planned prolapse surgery less than 3 months from enrollment
• Presence of vaginal fistulas
• Pessary self-care (patient changes and cleans her own pessary)
• Receiving immunosuppressive therapy or history of immunodeficiency
• Presence of an indwelling vascular access line or structural heart disease
• Within 6 weeks from any abdominal or pelvic surgery or other major surgery
• Allergy to lactobacillus (contents of probiotic)
• Allergy to beta-lactam antibiotics, erythromycin and clindamycin
• Use of any probiotic pills, creams, or suppositories currently

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vaginal Probiotic Arm; BiopHreshTM vaginal probiotic supplement (Good Clean Love, Inc. Eugene, OR) is offered over the counter. It contains a total of 5 billion lactobacilli: L. crispatus, L. gasseri, L. jensenii, and L. rhamnosus. RestoreTM gel: moisturizing personal lubricant. We will recommend to participants to use the probiotic supplement and vaginal lubricant as a vaginal suppository three times weekly at night for 3 months.	Other: BiopHreshTM vaginal probiotic supplement (Good Clean Love, Inc. Eugene, OR) and RestoreTM gel.; BiopHreshTM is a vaginal probiotic supplement that is offered over the counter and contains four different lactobacilli strains (L. crispatus, L. gasseri, L. jensenii, and L. rhamnosus). RestoreTM is a moisturizing personal lubricant that has been on the market for three years. Participants will use 1 probiotic capsule with RestoreTM gel nightly three times weekly.
Other: Standard Care Arm; Women will perform standard care which includes follow up at 3 months for pessary removal/care.	Other: Standard Care; Standard care arm is standard care for pessary use. Pessary maintenance will be performed standardly by their provider.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in vaginal microenvironment	Change in vaginal microenvironment on gram stain measuring lactobacilli, anaerobic bacteria, and mobiluncus, WBCs and epithelial cell maturation reported as Nugent Subscore.	Vaginal specimen assessment with gram stain will be assessed upon enrollment and after 3 months of treatment.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pelvic Floor Disability Index (PFDI-20)	The PFDI-20 will be used in order to evaluate pelvic floor symptoms.	Participants will complete the PFDI-20 upon enrollment and after 3 months of treatment.
Vaginal probiotic feasibility, compliance with, and side effects of probiotic use.	Unvalidated questionnaires (vaginal products and hromonal therapy questionnaire, subjective vaginal experiences over the past month questionnaire, and a vaginal probiotic questionnaire) were created in order to evaluate participant experiences with vaginal probiotics including feasibility, impact on symptoms from pessary use, and side effects from use. These questionnaires do not have scales.	Participants will complete after 1 month of use as well as at 3 months.
Urinary tract infection incidence	Occurrences of urinary tract infections during the study period will be monitored.	During participant involvement in the study 3-4 months.
BVAB-1	Evaluate the incidence of BVAB-1 and impact of vaginal probiotics on BVAB-1 in postmenopausal women via gram stain.	Vaginal specimen will collect from participants upon enrollment and after 3 months.
Pro-inflammatory cytokines (Interleukin (IL-6)), Tumor Necrosis Factor-alpha (TNF-alpha), Interleukin(IL-1alpha) and Interleukin (IL-1beta)	Pro-inflammatory cytokines will be evaluated from vaginal specimens collected in order to evaluate (1) the impact of probiotics on the inflammatory environment of the vagina (2) longitudinal assessment of pro-inflammatory cytokines in pessary wearing patients.	Vaginal specimens will be collected for cytokine analysis at enrollment and after 3 months
Incidence of adverse events (safety and tolerability)	number of adverse events (vaginal irritation)	from enrollment to 3 month follow up visit

Collaborators and Investigators

• Sponsor: Hartford Hospital
• Collaborators: University of Maryland; University of Connecticut
• Investigators: Principal Investigator: Elisabeth Sappenfield, MD, Hartford Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 30, 2019
• Primary Completion (Actual): May 30, 2021
• Study Completion (Actual): May 30, 2021

Study Registration Dates

• First Submitted: October 1, 2019
• First Submitted That Met QC Criteria: October 4, 2019
• First Posted (Actual): October 7, 2019

Study Record Updates

• Last Update Posted (Actual): March 25, 2022
• Last Update Submitted That Met QC Criteria: March 24, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Probiotics; Cytokines; Pessary use; Microenvironment
• Additional Relevant MeSH Terms: Pathologic Processes; Pathological Conditions, Anatomical; Prolapse; Pelvic Organ Prolapse; Dysbiosis
• Other Study ID Numbers: R-HHC-2019-0069

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No