Probiotic Efficacy in Postmenopausal Women with Bacterial Vaginosis

October 24, 2024 updated by: Yenti Purnamasari, Hasanuddin University

Modulation of Vaginal Microbiota by Lactobacillus Sp As a Probiotic and Immunomodulatory Agent in Postmenopausal Women with Bacterial Vaginosis

This study is a double-blind, randomized, controlled trial (RCT) aimed at evaluating the effects of Lactobacillus sp. probiotic administration on the vaginal microbiota changes in postmenopausal women with bacterial vaginosis and how its affect to immunology profile. Postmenopausal women diagnosed with bacterial vaginosis will be recruited as subjects as long as collected period in this study. All patients will receive Metronidazole antibiotic treatment then blind-randomly be divided into two groups: the treatment group, receiving Floragyn® probiotic tablets (Lapi, Indonesia), and the placebo group, receiving Cal 95® (Lapi, Indonesia). As a control, postmenopausal women without bacterial vaginosis will also be included and receive Floragyn® probiotic tablets only.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Postmenopausal women experience hormonal changes, particularly in estrogen and progesterone levels. The reduction or even cessation of estrogen secretion in postmenopausal women leads to an increased dominance of pathogenic bacteria in the vagina, which during the premenopausal period was inhibited by Lactobacillus sp. The presence of Lactobacillus in the vaginal epithelium acts as a barrier against external pathogens and produces metabolic byproducts that are unfavorable for the growth of other bacteria. The availability of glycogen, which is influenced by estrogen levels, supports the presence of Lactobacillus as an energy source. This association explains why women entering menopause are at increased risk of developing bacterial vaginosis. In addition, it is known that female reproductive hormones regulate both innate and adaptive immune responses and modulate endocrine functions that influence Th1 and Th2 cytokines, suppress excessive inflammation, and restore homeostasis.

This study conduct to investigate the effects of probiotic therapy on the vaginal microbiota changes in menopausal women and its impact on immunological profiles. Administering Lactobacillus sp. probiotics is expected to modulate bacterial growth disrupted during perimenopause and help restore homeostasis.

All postmenopausal women, during sample collected period, who meet the inclusion criteria will be enrolled as research subjects. Initially, vaginal swabs and venous blood samples will be collected to assess the bacterial vaginosis condition and hematological profiles. Once bacterial vaginosis is diagnosed, subjects will receive standard antibiotic therapy, metronidazole oral 400-500 mg twice daily or 0,75% metronidazole gel 5 grams intravaginally once daily for 5 days. 48 hours after antibiotic administration, participants will be randomly divided into two groups: the treatment group, receiving Floragyn® probiotics, and the placebo group, receiving Cal95®. Probiotic or placebo treatment will be administered orally once daily for two weeks. A healthy control group will also be included for comparison and will receive Floragyn® for two weeks.

Four weeks after the last probiotic dose, vaginal swabs and venous blood samples will be collected. The analysis will include pH, glucose, protein levels, and microbiome composition from the vaginal swabs, while venous blood samples will be analyzed for interleukin 6 and 10 levels, as well as inflammatory markers such as platelets, leukocytes, and differential leukocyte counts. The collected data will be analyzed to evaluate microbiome alterations and inflammatory markers in the treatment and placebo groups.

Study Type

Interventional

Enrollment (Estimated)

12

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Indonesia
    • South East Sulawesi
      • Kendari, South East Sulawesi, Indonesia, 93117
        • Recruiting
        • Alfa Farma Health Clinic, Obstetrics and Gynecology Doctor's Practice.
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  1. Postmenopausal with estradiol levels < 25 mg/ml
  2. Diagnosed have bacterial vaginosis by an obstetrician and gynecologist

Exclusion Criteria:

  1. Medically unable to perform a pap smear examination
  2. Experiencing vaginal bleeding of unknown cause
  3. Diagnosed or suspected of having a malignant disease
  4. Hypersensitivity to the research treatment to be carried out
  5. In the last 3 months have received hormone therapy
  6. Suffering from acute infectious diseases of the genital organs
  7. Using vaginal therapy in any form
  8. Suffering from systemic diseases

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Intervention
This group consist of postmenopausal women diagnosed with bacterial vaginosis. All subjects will receive metronidazole oral 400-500 mg twice daily or 0,75% metronidazole gel 5 grams intravaginally once daily for 5 days, then blind-randomly including to the treatment group and will receive Floragyn® probiotic tablets (Lapi, Indonesia) orally once daily for two weeks.
Dietary supplement: Metronidazole + Floragyn® probiotic tablets (Lapi, Indonesia)

Metronidazole, sold under the brand name Flagyl among others, is an antibiotic and antiprotozoal medication. It is used either alone or with other antibiotics to treat pelvic inflammatory disease, endocarditis, and bacterial vaginosis. It is effective for dracunculiasis, giardiasis, trichomoniasis, and amebiasis.

One tablet Floragyn contains Lactobacillus rhamnosus and lactobacillus reuteri, bacteria that are normal flora (good bacteria) of the vagina.
Placebo Comparator: Placebo
This group consist of postmenopausal women diagnosed with bacterial vaginosis. All subjects will receive metronidazole oral 400-500 mg twice daily or 0,75% metronidazole gel 5 grams intravaginally once daily for 5 days, then blind-randomly including to the placebo group and will receive Cal95® probiotic tablets (Lapi, Indonesia) orally once daily for two weeks.
Dietary supplement: Metronidazole + Cal95

Metronidazole, sold under the brand name Flagyl among others, is an antibiotic and antiprotozoal medication. It is used either alone or with other antibiotics to treat pelvic inflammatory disease, endocarditis, and bacterial vaginosis. It is effective for dracunculiasis, giardiasis, trichomoniasis, and amebiasis.

Cal 95 is a supplement containing multivitamins and minerals including: Calcium, Zinc, Boron and Magnesium. This tablet is used to help meet calcium needs and maintain bone health in menopausal women.
Active Comparator: Control
This group consist of postmenopausal women with no bacterial vaginosis. All subjects will receive Floragyn® probiotic tablets (Lapi, Indonesia) orally once daily for two weeks.
Dietary supplement: Floragyn® probiotic tablets (Lapi, Indonesia)
Given to the control group to ensure the ability of probiotics to maintain a healthy vaginal ecosystem and not the opposite.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Bacterial Vaginosis Status
Time Frame: At 0, 1, and 7 weeks duration of trial
A health status of woman reproduction diagnosed by nugent score. Nugent score calculations are carried out by looking at bacterial morphology ie Lactobacillus (parallel - sided, gram positive rods), Mobilincus (curved - Gram negative rods), and Gardnerella / Bacteriodes (tiny, gram-variable cocobacilli and rounded, pleomorphic, gram-negative rods with vacuoles). Score 0-3 is normal flora, score 4-6 is intermediate, score 7-10 is bacterial vaginosis.
At 0, 1, and 7 weeks duration of trial

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Total Leukocyte Count
Time Frame: 0 and 7 weeks duration of trial
Leukocytes function to detect and fight microorganisms or foreign pathogens that can cause disease, such as viruses, fungi, bacteria, and parasites. Increased levels in the body can be a sign of an ongoing inflammatory process. Leukocyte levels in this study were taken using venous blood samples. its level is expressed in units of 10^3/uL and normal values are 4-10 10^3/uL.
0 and 7 weeks duration of trial
Eosinophil Levels
Time Frame: 0 and 7 weeks duration of trial
Eosinophils are white blood cells that have a primary function in fighting infections and responding to various types of allergens in the body. Eosinophil levels that exceed the normal range should be watched out for because they can indicate an inflammatory disease. Calculation of eosinophil levels is done using venous blood samples. Eosinophil levels are expressed in % units and normal values are 2-4%.
0 and 7 weeks duration of trial
Monocytes level
Time Frame: 0 and 7 weeks duration of trial
This type of white blood cell functions to capture and fight attacks by fungi, bacteria, viruses, or parasites that enter the body. The normal level of monocytes is around 2-8% of the total number of white blood cells in the body. The sample used for measurement is venous blood.
0 and 7 weeks duration of trial
Lymphocytes level
Time Frame: 0 and 7 weeks duration of trial
Lymphocytes are white blood cells that play an important role in protecting the body from various infectious diseases. In addition, the level of lymphocytes in the body can also be a sign of certain medical conditions such as infection and inflammation. The normal level of monocytes is around 20-40% of the total number of white blood cells in the body. The sample used for measurement is venous blood.
0 and 7 weeks duration of trial
Interleukin-6 level
Time Frame: 0 and 7 weeks duration of trial
Interleukin-6 is a cytokine secreted from body tissues into blood plasma, especially in acute or chronic infection phases, and induces an inflammatory response. The sample used to assess interleukin 6 levels is venous blood with a normal value of interleukin 6 in the blood being <4 pg/ml.
0 and 7 weeks duration of trial
Interleukin-10 level
Time Frame: 0 and 7 weeks duration of trial
Interleukin-10 is a cytokine abundantly secreted by monocytes, which has pleiotropic effects on the immune system and inflammation by inhibiting the activation and effector functions of T cells, monocytes and macrophages. The sample used to assess interleukin 10 levels is venous blood with a normal value of interleukin 10 in the blood being <18 pg/ml.
0 and 7 weeks duration of trial

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hasanuddin University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 26, 2024

Primary Completion (Estimated)

December 31, 2024

Study Completion (Estimated)

December 31, 2024

Study Registration Dates

First Submitted

October 23, 2024

First Submitted That Met QC Criteria

October 24, 2024

First Posted (Actual)

October 26, 2024

Study Record Updates

Last Update Posted (Actual)

October 28, 2024

Last Update Submitted That Met QC Criteria

October 24, 2024

Last Verified

October 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • B3/UN4.6.4.5.31-1/ PP36 / 2024

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

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Subscribe