Clinical trial NCT05918848: Tocopherol Acetate Vaginal Administration in Pre-peri and Postmenopausal Women
Official title: Performance and Safety of Vaginal Administration of Tocopherol Acetate (Vitamin E) in Pre- Peri and Postmenopausal Women
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Pre- Peri, and Postmenopausal Women
Keywords: Premenopause
perimenopause
postmenopause
vaginal eubiosis
lactobacilli flora
microbiota
Lead sponsor: Gemelli Molise Hospital
Sponsor class: OTHER
Collaborators: name: Opera CRO, a TIGERMED Group Company
First posted: 2023-06-26
Enrollment: 50
Sex: FEMALE
Minimum age (years): 50
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The patients admitted in the Center for gynecologic visits in the period from January 1st, 2020 to December, 31st, 2022 and found eligible for inclusion in the study.

Brief summary: The purpose of this non-controlled Investigator Initiated Trail (IIT), with a retrospective design is to evaluate the performance and safety of the vaginal administration of tocopherol acetate (vitamin E) in pre-peri and postmenopausal women. The main objectives of the study will be the evaluation of the vaginal pH, of the vaginal eubiosis improving the lactobacilli flora and microbiota, and of sign and symptoms of women. The patients were visited at baseline (with the collection of vaginal swabs) and treated with vaginal administration of tocopherol acetate for 14 days. At the end of treatment (final visit) the patients were visited with the collection of vaginal swabs.

Detailed description: The vaginal microbiota has a significant bearing on a woman's mental and physical health at every stage of life. A balanced microflora of the vaginal environment (eubiosis) consists of a predominant presence of lactic acid bacteria. Lactobacilli ensure the maintenance of an acidic pH that effectively makes the environment inhospitable to pathogens by preventing infection and protecting the genital tract. At the end of the reproductive period, the reduction of sex hormones, particularly estrogen, results in a decrease in the lactobacillus component with consequent depletion of the vaginal microbiota and increased susceptibility to pathogens. Tocopherol (vitamin E) is an essential human nutrient found mainly in oily fruits. It is a fat-soluble molecule with high antioxidant power. Topically administered, it not only plays a key role in protecting epithelial cell membranes from oxidative damage but is also able to modulate bacterial growth by contributing to pH acidification. The latter feature, in the vaginal canal, creates a favorable environment for the lactobacilli flora, positively affecting the microbial population and thus contributing to the prevention of all those problems related to increased vaginal sensitivity to pathogens during "menopause." In addition, recent data show that vitamin E can counteract the production of biofilm produced by certain pathogens, which has detrimental effects on the homeostasis of the vaginal environment.

The period of observation is from January 1st, 2020 to December, 31st, 2022, while the Data Collection period will be from June, 30th, 2023 to July, 31st, 2023

Eligibility criteria: Inclusion Criteria:

* Women aged ≥ 50 to ≤ 70 years included.
* Premenopause, perimenopause,postmenopause women (according to STRAW criteria)
* Patients able to comply with the requirements for the study and freely willing to provide written informed consent to the retrospectively collection of their data.

Exclusion Criteria:

* Malignancy (also leukemic infiltrates) within 5 years prior to day 0 (except for treated basal cell/squamous cell carcinoma of the skin).
* Genital bleeding.
* Oestrogen topical (vaginal) treatment during the study period (it must have been terminated at least 6 months before the beginning of the study).
* Systemic oestrogen therapy during the study period (it must have been terminated at least 6 months before the beginning of the study).
* Patients with any illness, or any other medical condition, that, in the opinion of the Investigator, would compromise the participation or be likely to lead to hospitalisation during the study.
* Clinical evidence of acute infection currently requiring treatment (syphilis, herpes simplex, human papilloma virus, gonorrhoea, chlamydia, lymphogranuloma venereum, etc.); clinical evidence or history of chronic infectious disease (e.g., tuberculosis).
* Psychosis, schizophrenia, mania, depressive disorders, history of suicide attempt or suicidal ideation, or any other psychiatric illness (except for intermittent anxiety).
* Known allergy to tested medical device (tocopherol day 0.
* Participation in an interventional clinical study or administration of any investigational agents in the 30 days prior to day 0.
* Presence of any clinically significant medical condition judged by the Investigator to preclude the patient's inclusion in the study.

Primary outcomes:
measure: Acidity measure of vaginal secretions
timeFrame: 14 days
Secondary outcomes:
measure: Rate of vaginal mucosa dryness
timeFrame: 14 days
measure: Rate of vaginal mucosal integrity
timeFrame: 14 days
measure: Rate of mucosa pallor
timeFrame: 14 days
measure: Quantity of vaginal discharge assessment
timeFrame: 14 days
measure: Whiff test
timeFrame: 14 days
measure: Rate of Lactobacillus grade according to Ison Hay's classification by bacterioscopic smear
timeFrame: 14 days
measure: Microbiological evaluation by culture examination of the vaginal swab
timeFrame: 14 days
measure: Molecular sequencing-based microbiological analysis of vaginal microbiota by next-generation sequencing (NGS) method.
timeFrame: 14 days
measure: Serious Adverse Device Effects / Serious Adverse Events /Adverse Device Effects/ Adverse Events
timeFrame: 14 days
Other outcomes:
Locations:
Study officials:
affiliation: U.O.C. Ginecologia Oncologica Gemelli Molise
name: Francesco Cosentino, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Microbiologia e Microbiologia Clinica Dipartimento Medicina e Scienze per la salute "V. Tiberio" Università degli Studi del Molise Campobasso (Italy) Laboratory
name: Roberto Di Marco, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Costantino D, Guaraldi C. Effectiveness and safety of vaginal suppositories for the treatment of the vaginal atrophy in postmenopausal women: an open, non-controlled clinical trial. Eur Rev Med Pharmacol Sci. 2008 Nov-Dec;12(6):411-6.
citation: Palma F, Volpe A, Villa P, Cagnacci A; Writing group of AGATA study. Vaginal atrophy of women in postmenopause. Results from a multicentric observational study: The AGATA study. Maturitas. 2016 Jan;83:40-4. doi: 10.1016/j.maturitas.2015.09.001. Epub 2015 Sep 14.
citation: Dimery IW, Hong WK, Lee JJ, Guillory-Perez C, Pham F, Fritsche HA Jr, Lippman SM. Phase I trial of alpha-tocopherol effects on 13-cis-retinoic acid toxicity. Ann Oncol. 1997 Jan;8(1):85-9. doi: 10.1023/a:1008209525671.
citation: Panin G, Strumia R, Ursini F. Topical alpha-tocopherol acetate in the bulk phase: eight years of experience in skin treatment. Ann N Y Acad Sci. 2004 Dec;1031:443-7. doi: 10.1196/annals.1331.069.
citation: Burton GW, Ingold KU. Vitamin E as an in vitro and in vivo antioxidant. Ann N Y Acad Sci. 1989;570:7-22. doi: 10.1111/j.1749-6632.1989.tb14904.x.