Reducing Abundance of Human Papilloma Virus in Women by Taking Probiotic

The Effects of Probiotic Against Reducing Abundance of Human Papilloma Virus (HPV) in Women

The purpose of this study is to evaluate the efficacy of oral administration of probiotic at 9 log colony forming unit (CFU)/day to reduce vaginal abundance of HPV in women compared to placebo via the use of vaginal self-swab.

Study Overview

• Status: Withdrawn
• Conditions: Human Papilloma Virus Infection
• Intervention / Treatment: Biological: probiotic; Other: placebo

Detailed Description

Probiotics have shown an antiviral activity and several mechanisms have been demonstrated. In respiratory tract infections (RTIs), the majority of probiotics can inhibit the most important respiratory viruses by immunomodulatory mechanisms. There are over 200 different types of viruses, which cause RTIs in humans. Human rhinoviruses (HRV) are the largest group of respiratory viruses, comprising over 150 serotypes. In humans, the predominant illness caused by HRV is the acute upper RTI, also known as the common cold. The second most common viruses infecting humans are the human enteroviruses (HEV), which are associated with clinical manifestations ranging from mild respiratory symptoms to serious conditions. Influenza viruses, respiratory syncytial virus (RSV), and adenoviruses are also major causative agents of both upper and lower RTIs. In addition, many other viruses or virus groups cause RTIs, e.g., parainfluenza viruses and coronaviruses can cause a broad spectrum of respiratory diseases, ranging from mild upper RTIs to pneumonia. In recent years, with the rapid development of high-throughput molecular techniques, several new viruses associated with respiratory diseases, such as human bocavirus, human metapneumovirus, and the new coronaviruses HKU1 and NL63, have been identified as well. Recently, COVID-19 had cause huge effect worldwide. With this, to reduce the burden and severity of this pandemic, the use of probiotic in preventing of COVID-19 has been ongoing. Probiotics also had given out significant outcome in gastroenteritis infections where a study suggested that probiotics had be effective in alleviating the duration and severity of acute rotavirus gastroenteritis. Apart from this, for viruses that cause hepatitis, skin virus infections, human immunodeficiency virus (HIV), or HPV, probiotics could directly or indirectly, help reduce their symptoms or prevent infection.

Probiotics are known as a good natural non-drug, which was widely used to boost immune cells in host to fight against infection. Generally, probiotic effects are mediated through immune regulation, particularly through balance control of proinflammatory and anti-inflammatory cytokines. The immune response is initiated by innate immunity following exposure to foreign substances or tissue injury. Innate immunity exerts protective roles in host homeostasis in part by priming adaptive immune responses against persisting insults and inducing inflammation. However, the unbalanced immune response leads to severe inflammation and uncontrolled tissue damage and disease. Probiotics have been found to enhance the innate immunity and modulate pathogen-induced inflammation via toll-like receptor-regulated signaling pathways.

• Study Type: Interventional
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Malaysia
  • Penang
    • Pulau pinang, Penang, Malaysia, 13700
      • Hospital Seberang Jaya

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 26 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Sexually active women
• Age above 26 years old
• Determined as HPV positive against L1 variant
• Willing to commit throughout the experiment

Exclusion Criteria:

• On long term medication (6 months and above) for any illnesses
• Pregnant
• Uterus and/or cervix removed
• Prior HPV vaccination
• Cervical intraepithelial neoplasia

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: probiotic 9 log CFU/day; Intervention consists of daily oral administration of one sachet/day of probiotic for 12 weeks, where each sachet contains 9 log CFU of probiotic.	Biological: probiotic; oral administration of probiotic at 9 log CFU/day for 12 weeks to reduce vaginal abundance of HPV in women compared to placebo via the use of vaginal self-swab.
Placebo Comparator: placebo; placebo contains primarily carrier without probiotic and it is identical in taste and appearance and appear as light-yellow powder. It is also taken by the participants for 12 weeks.	Other: placebo; oral administration of primarily carrier without the probiotic for 12 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in vaginal abundance of HPV of women upon administration of probiotic.	Differences in vaginal HPV abundance in women upon administration of probiotic at 9 log CFU/day compared to placebo via real-time PCR quantification of the L1 capsid gene as a conserved region of the HPV genome using consensus primers PGMY09 and PGMY1.	12-weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in vaginal microbiota of women upon administration of probiotic.	Differences in vaginal microbiota in women upon administration of probiotic at 9 log CFU/day compared to placebo via microbiota profiling using DNA of vaginal samples amplified for bacterial 16S rRNA and analyzed for high-throughput community sequencing.	12-weeks
Changes in gut microbiota of women upon administration of probiotic.	Differences in gut microbiota profiles of women on probiotic and placebo via microbiota profiling using DNA of fecal samples amplified for bacterial 16S rRNA and analyzed for high-throughput community sequencing.	12-weeks
Changes in vaginal health of women upon administration of probiotic via the use of questionnaire.	Differences in total scores of women upon administration of probiotic at 9 log CFU/day compared to placebo via the use of vulvovaginal symptom questionnaire (VSQ) containing 21-items on a two-point scale with higher scores indicating poorer health status.	12-weeks
Changes in immunity of women upon administration of probiotic 9 log CFU/day as assessed via biochemical tests.	To evaluate differences in immunity of women on probiotic and placebo in terms of blood immunity profiling via measuring concentrations of immunoglobulins such as IgA, IgG and IgM, and cytokines such as interleukin (IL)-1b, IL-4, IL-10, TNF-α and IFN-γ using commercially available ELISA kits.	12-weeks

Collaborators and Investigators

• Sponsor: Universiti Sains Malaysia
• Investigators: Study Director: MingTze Liong, Doctor, School of Industrial Technology USM; Principal Investigator: Binti Sany Salina, Doctor, Institut Perubatan & Pergigian Termaju USM

Study record dates

Study Major Dates

• Study Start (Actual): December 27, 2021
• Primary Completion (Estimated): November 28, 2023
• Study Completion (Estimated): November 28, 2023

Study Registration Dates

• First Submitted: March 17, 2022
• First Submitted That Met QC Criteria: March 29, 2022
• First Posted (Actual): April 7, 2022

Study Record Updates

• Last Update Posted (Actual): May 10, 2024
• Last Update Submitted That Met QC Criteria: May 8, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: probiotics; human papilloma virus
• Additional Relevant MeSH Terms: Pathologic Processes; Virus Diseases; Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Disease Attributes; DNA Virus Infections; Tumor Virus Infections; Neoplasms, Squamous Cell; Urogenital Diseases; Genital Diseases; Papillomavirus Infections; Papilloma
• Other Study ID Numbers: NMRR-21-1819-61300 (IIR)

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