Effects of Chinese Medicine and Lactobacillus in Persistent HPV Infection (ELIMVLHPV)

Effects of Estrogen-like Chinese Medicine and Vaginal Lactobacillus on HPV Clearance and Vaginal Microbiota Change in Women With Persistent HPV Infection

High risk human papillomavirus (hr-HPV) persistent infection is a high risk factor for cervical cancer. 85% to 90% of hr-HPV infections have the ability to clear on their own, while 10% to 15% of HPV persists further will lead to the development of high-grade intraepithelial lesions (HSIL) and even to invasive cervical cancer. Long-term follow-up results for persistent hr-HPV infection showed that cervical HSIL mostly occurred after 5-7 years of persistent hr-HPV infection, among which the risk of HPV16 and 18 was the highest, followed by HPV31 and 33. The role of the vaginal microbiome (CVM) in persistent hr-HPV infection has been increasingly valued, and women with persistent HPV infection that progresses to HSIL have a more unstable vaginal microenvironment. The previous study found that Lactobacillus vaginalis may contribute to HPV clearance by improving the vaginal microenvironment. In addition, previous studies have found that estrogen-like Chinese medicine could increase glycogen, improve mucosal estrogen levels, increase lactobacillus content, and promote HPV clearance. It is a challenge to make clinical management on when and how to intervene among hr-HPV persistent infection but whose pathology does not suggest HSIL. This study intends to analyze the correlation between the duration of HPV infection and the current vaginal microbiome, HPV load and PAX1 methylation in people with persistent HPV infection at different ages, and observe the changes of the above indicators after the administration of drugs to improve the vaginal microenvironment, which is helpful for preventing HPV persistent infection and developing into true precancerous lesions. It has the clinical and practical value of "preparing for a rainy day".

Study Overview

• Status: Recruiting
• Conditions: Human Papilloma Virus Infection
• Intervention / Treatment: Drug: Chinese medicine and Lactobacillus; Drug: Chinese medicine; Drug: Lactobacillus

Detailed Description

1. Correlation of Previous Persistent HPV Infection Duration with Current CST, HPV Load, and PAX1 Methylation Participants: Select 240 women aged 25 and above who have had persistent high-risk HPV infection of the same type for 1 year or more but whose pathology does not indicate HSIL.

   Data Recording: Record the time of first confirmed HPV infection based on test reports.

   Initial Testing: After meeting the inclusion criteria, conduct initial tests for vaginal microbiota types (CST), HPV load, and PAX1 methylation.

   Correlation Analysis: Analyze the correlations based on different ages, menopausal status, and duration of HPV infection.

2. Changes in CST, HPV Load, and PAX1 Methylation After Treatment to Improve Vaginal Microenvironment

Study Design: Conduct a double-blind randomized medication trial with the participants divided into four groups:

Traditional Chinese Medicine Group: 10 days Lactobacillus Group: 10 days Combination Group: Traditional Chinese Medicine for 5 days + Lactobacillus for 5 days Control Group: Observation only, no medication Pre-Treatment: If applicable, treat any existing vaginitis before assigning medications.

Medication Regimen: Administer 10 consecutive days of vaginal medication each month, pausing during menstruation and resuming post-menstruation to complete the 10-day course. Sexual intercourse is prohibited during the medication period.

Follow-Up Testing: Conduct CST, HPV load, and PAX1 methylation tests at 6 and 12 months post-treatment.

Progression Monitoring: If HPV remains positive upon retesting, perform a colposcopy. Terminate the study and provide appropriate treatment if pathology progresses to HSIL.

• Study Type: Interventional
• Enrollment (Estimated): 240
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Mingzhu Li, doctor; Phone Number: 86+15910691947; Email: mingzhu1815@163.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100044
      • Recruiting
      • Peking University People's Hospital
      • Contact: Mingzhu Li

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Women over 25 years of age with the same type of high-risk HPV infection lasting for more than 1 year, atypical squamous cell (ASCUS) or Low-grade squamous intraepithelial disease (LSIL) cytologically negative or undiagnosable, and pathological biopsy results negative or LSIL
• Consent to use the device for contraception during the study period;
• agree with medicine and follow-up management procedure.

Exclusion Criteria:

• High cytological risk, including atypical squamous cells (ASC-H),HSIL and atypical glandular cell (AGC), which could not rule out high-grade squamous intraepithelial lesions;
• pathological biopsy for HSIL and above;
• for any drug allergies;
• pregnancy or lactation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: observation group; Observation and follow-up only, no medication
Experimental: combined drug group; Chinese medicine 5 days + Lactobacillus 5 days	Drug: Chinese medicine and Lactobacillus; combined drug group; Other Names: Baofukang and Dingjunsheng
Active Comparator: Single Chinese medicine group; Chinese medicine group 10 days	Drug: Chinese medicine; Single Chinese medicine group; Other Names: Baofukang
Active Comparator: Single Lactobacillus group; Lactobacillus group: 10 days	Drug: Lactobacillus; Single Lactobacillus group; Other Names: Dingjunsheng

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
community state type (CST)	Vaginal microflora type	Change of CST at 6 months and 12 months after medication
HPV VL	HPV viral load	Change of HPV VL at 6 months and 12 months after medication
PAX1 methylation test	Pairing box gene1 methylation test	Change of PAX1 methylation test at 6 months and 12 months after medication

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete remission (CR)	HPV subtypes with persistent infection turned negative at 6 and 12 months or positive at 6 months, and negative at 12 months	Change of CR at 6 months and 12 months after medication
Partial remission (PR)	Partial response (PR) : HPV subtypes with persistent infection turned negative at 6 months and returned positive at 12 months	Change of PR at 6 months and 12 months after medication
No response (NR)	HPV subtypes with persistent infection were positive at both follow-up visits	Change of NR at 6 months and 12 months after medication

Collaborators and Investigators

• Sponsor: Peking University People's Hospital
• Investigators: Principal Investigator: Mingzhu Li, Peking University People's Hosptial

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2023
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: February 17, 2023
• First Submitted That Met QC Criteria: June 15, 2024
• First Posted (Actual): June 21, 2024

Study Record Updates

• Last Update Posted (Actual): June 21, 2024
• Last Update Submitted That Met QC Criteria: June 15, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Virus 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; Infections; Communicable Diseases; Papillomavirus Infections; Papilloma
• Other Study ID Numbers: ELIM-HPV2023

Drug and device information, study documents

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