Clinical trial NCT06659380: Probiotic Efficacy in Postmenopausal Women with Bacterial Vaginosis
Official title: Modulation of Vaginal Microbiota by Lactobacillus Sp As a Probiotic and Immunomodulatory Agent in Postmenopausal Women with Bacterial Vaginosis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Bacterial Vaginosis (BV)
Menopause
Keywords: NO
Lead sponsor: Hasanuddin University
Sponsor class: OTHER
First posted: 2024-10-26
Enrollment: 12
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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. Patients are assessed at T0, T1 and T7 week.
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Bacterial Vaginosis Status
timeFrame: At 0, 1, and 7 weeks duration of trial
Secondary outcomes:
measure: Total Leukocyte Count
timeFrame: 0 and 7 weeks duration of trial
measure: Eosinophil Levels
timeFrame: 0 and 7 weeks duration of trial
measure: Monocytes level
timeFrame: 0 and 7 weeks duration of trial
measure: Lymphocytes level
timeFrame: 0 and 7 weeks duration of trial
measure: Interleukin-6 level
timeFrame: 0 and 7 weeks duration of trial
measure: Interleukin-10 level
timeFrame: 0 and 7 weeks duration of trial
Other outcomes:
Locations:
city: Kendari
country: Indonesia
facility: Alfa Farma Health Clinic, Obstetrics and Gynecology Doctor's Practice.
state: South East Sulawesi
Study officials:
References:
citation: Munoz-Barreno A, Cabezas-Mera F, Tejera E, Machado A. Comparative Effectiveness of Treatments for Bacterial Vaginosis: A Network Meta-Analysis. Antibiotics (Basel). 2021 Aug 13;10(8):978. doi: 10.3390/antibiotics10080978.
citation: Cohen CR, Wierzbicki MR, French AL, Morris S, Newmann S, Reno H, Green L, Miller S, Powell J, Parks T, Hemmerling A. Randomized Trial of Lactin-V to Prevent Recurrence of Bacterial Vaginosis. N Engl J Med. 2020 May 14;382(20):1906-1915. doi: 10.1056/NEJMoa1915254.
citation: France M, Alizadeh M, Brown S, Ma B, Ravel J. Towards a deeper understanding of the vaginal microbiota. Nat Microbiol. 2022 Mar;7(3):367-378. doi: 10.1038/s41564-022-01083-2. Epub 2022 Mar 4.
citation: Laniewski P, Herbst-Kralovetz MM. Connecting microbiome and menopause for healthy ageing. Nat Microbiol. 2022 Mar;7(3):354-358. doi: 10.1038/s41564-022-01071-6.
citation: Peacock K, Carlson K, Ketvertis KM. Menopause. 2023 Dec 21. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from http://www.ncbi.nlm.nih.gov/books/NBK507826/
citation: Peebles K, Velloza J, Balkus JE, McClelland RS, Barnabas RV. High Global Burden and Costs of Bacterial Vaginosis: A Systematic Review and Meta-Analysis. Sex Transm Dis. 2019 May;46(5):304-311. doi: 10.1097/OLQ.0000000000000972.