HPV infection clearance with glucan and probiotics

Plain English Summary

Background and study aims
The aim of this study is to measure the effectiveness and safety of local treatment with a vaginal gel based on carboxy-methyl-beta-glucan in polycarbophil plus an oral probiotic containing an L. rhamnosus TOM 22.8 strain on genital human papillomavirus (HPV) infections. HPV is estimated to infect up to 80% of sexually active women by age 50 years. Although most HPV infections resolve over time, persistent infection can cause precancerous lesions and eventually lead to invasive cancer, mainly at the cervix. Nevertheless, HPV presence alone is not enough for cancer formation and local immunity in conjunction with low numbers of vaginal lactobacilli (bacteria) seem to be pivotal in cancer development. Beta-glucans have several roles in the human body such as increasing resistance to infectious diseases and a modulator action for the immune system. Probiotics have been studied in the context of HPV with study outcomes aimed at enhanced genital viral clearance

Who can participate?
Patients with low-grade pap smear anomalies or with a positive HPV DNA test

What does the study involve?
Participants are randomly allocated into four groups:
Group 1. Treatment with one capsule a day for 10 days per month for 3 months containing Lactobacillus rhamnosus TOM 22.8 10 x 10e9 U.F.C and vaginal gel-based carboxy-methyl-beta-glucan one application/day for 20 days per month for 3 months
Group 2. Treatment with one capsule a day for 10 days per month for 3 months containing Lactobacillus rhamnosus TOM 22.8 10 x 10e9 U.F.C., immediately after the end of each menstrual period
Group 3. Treatment with vaginal gel-based carboxy-methyl-beta-glucan 1 application/day for 20 days per month for 3 months, immediately after the end of each menstrual period
Group 4: Untreated women, as the control group
On study day 180 (follow-up visit) the Pap test, HPV-DNA test, colposcopy and vaginal samples are taken to evaluate bacteria. In Groups 1, 2 and 3 compliance, treatment security, and allergic reactions will be also evaluated.

What are the possible benefits and risks of participating?
The treatment may resolve pap smear anomalies and eliminate HPV infection. The researchers are not aware of adverse events related to the treatment.

Where is the study run from?
Ospedale dei Bambini Vittore Buzzi (Italy)

When is the study starting and how long is it expected to run for?
June 2022 to June 2023

Who is funding the study?
Investigator initiated and funded

Who is the main contact?
Prof. Filippo Murina, filippo.murina@unimi.it

Study website

Type

Principal Investigator

Contact name

Prof Ilippo Murina

ORCID ID

Contact details

Via Castelvetro
Milano
20122
Italy
+39 (0)263631
filippo.murina@unimi.it

EudraCT/CTIS number

Nil known

IRAS number

ClinicalTrials.gov number

Nil known

Protocol/serial number

SDSM-2021-01.1

Scientific title

Effects on cervical high-risk human papillomavirus clearance in patients undergoing treatment with vaginal gel based on carboxy-methyl-beta-glucan in polycarbophil plus an oral probiotic containing L. rhamnosus TOM 22.8 strain: a randomized controlled trial

Acronym

HPGC

Study hypothesis

The aim of this study is to prospectively document the efficacy and safety of local therapy with a vaginal gel based on carboxy-methyl-beta-glucan in polycarbophil plus an oral probiotic containing L. rhamnosus TOM 22.8 strain on genital high-risk human papillomavirus (HR-HPV) clearance and low-grade squamous intraepithelial lesion (LSIL)/cervical intraepithelial neoplasia (CIN) 1 regression.

Ethics approval(s)

Not provided at time of registration

Study design

Single-center randomized controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Study setting(s)

Hospital

Study type

Treatment

Patient information sheet

Not available in web format, please use the contact details to request a participant information sheet

Condition

HPV infection

Intervention

Patient recruitment: PAP smears with mild anomalies (atypical squamous cells of undetermined significance [ASCUS] or LSIL) and/or a cervical biopsy-confirmed CIN 1, and a positive HPV DNA test. HPV infection will be detected using polymerase chain reaction (PCR) amplification of the viral DNA, followed by dot blot hybridization. At time zero, a vaginal sample will be obtained through a rubbed swab against the vaginal wall finalized to evaluate bacterial community composition by sequencing the 16S rRNA genes amplified from total genomic DNA isolated from the samples.

Randomization is determined by a computer-generated number list (MedCalc Version 20.110). The study population will be randomized into four groups:
Group 1. Treatment with one capsule a day for 10 days per month for 3 months containing Lactobacillus rhamnosus TOM 22.8 10 x 10e9 U.F.C and vaginal gel-based carboxy-methyl-beta-glucan one application/day for 20 days per month for 3 months. The protocol will start immediately after the end of each menstrual period
Group 2. Treatment with one capsule a day for 10 days per month for 3 months containing Lactobacillus rhamnosus TOM 22.8 10 x 10e9 U.F.C., immediately after the end of each menstrual period
Group 3. Treatment with vaginal gel-based carboxy-methyl-beta-glucan 1 application/day for 20 days per month for 3 months, immediately after the end of each menstrual period
Group 4: Untreated women, as the control group

On study day 180 (follow-up visit) the Pap test, HPV-DNA test, colposcopy and vaginal sample to evaluate bacterial community composition by sequencing the 16S rRNA genes will be repeated. In Groups 1, 2 and 3 compliance, treatment security, and allergic reactions will be also evaluated.

Intervention type

Supplement

Primary outcome measure

HR-HPV clearance measured using PCR at 6 months

Secondary outcome measures

LSIL/CIN 1 regression measured using Pap smear/histology at 6 months

Overall study start date

01/06/2022

Overall study end date

30/06/2023

Reason abandoned (if study stopped)

Participant inclusion criteria

1. Women aged 30-45 years
2. Persistent positive cytological LSIL and/or histological CIN 1 and/or HPV HR test for at least 12 months
3. Absence of contraindications to the proposed therapies
4. Read and signed informed consent

Participant type(s)

Patient

Age group

Adult

Sex

Female

Target number of participants

80 patients total, 20 for each group

Participant exclusion criteria

1. Active vulvovaginal infections at the time of their gynaecological examination
2. Genital bleeding of unknown origin
3. Pregnancy
4. Menopause (absence of menstruation for 12 months)
5. Diagnosis of or under therapy for previous CIN2+ lesions
6. Immune-depressed, or with infections caused by human immunodeficiency virus (HIV-positive)
7. Patients concomitantly included in different interventional clinical trials
8. Unwillingness to provide informed consent to the trial

Recruitment start date

01/06/2022

Recruitment end date

31/12/2022

Countries of recruitment

Italy

Study participating centre

Ospedale dei Bambini Vittore Buzzi
Lower Genital Tract Unit
Obst. and Gyn Dept.
Via Castelvetro 22
Milano
20122
Italy

Organisation

Ospedale dei Bambini Vittore Buzzi

Sponsor details

Lower Genital Tract Unit
Obst. and Gyn Dept.
Via Castelvetro 22
Milan
20122
Italy
+39 (0)250042000
info@vulvodinia.org

Sponsor type

Hospital/treatment centre

Website

https://ospedaledeibambini.it/noi-e-il-buzzi/

ROR

https://ror.org/044ycg712

Funder type

Other

Funder name

Investigator initiated and funded

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Publication and dissemination plan

The researchers plan to publish the study around September 2023.

Intention to publish date

01/09/2023

Individual participant data (IPD) sharing plan

The data-sharing plans for the current study are unknown and will be made available at a later date

IPD sharing plan summary

Data sharing statement to be made available at a later date

Study outputs