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HPV InfectionNCT07697196

Effect of EGCG, Folic Acid, Vitamin B12 and Hyaluronic Acid on HPV DNA Integration

A study testing Epigallocatechin gallate (EGCG), Folic Acid (FA), Vitamin B12 (B12), and Hyaluronic Acid (HA) in people with HPV Infection and HPV Integration, run by IRCCS San Raffaele at 1 site in Italy.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
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Trial summary

This interventional, single-center, open-label randomized clinical study evaluates the efficacy of an oral dietary supplement (Pervistop®) in women with persistent Human Papillomavirus (HPV) infection. Read more about this study

Who is it for?
Ages 25 years and older, women only
Conditions the study is for
HPV Infection, HPV Integration, HPV Disease
What is being tested?
Epigallocatechin gallate (EGCG), Folic Acid (FA), Vitamin B12 (B12), and Hyaluronic Acid (HA)
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
42 participants
Where
1 siteItaly
Study dates
Jul 2026to Jun 2028
Phase
Interventional
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 25 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age ≥ 25 years old
  • Positive HPV DNA test with genotyping 9-24 months prior to Day 0
  • Positive HPV DNA test with genotyping at Day 0
  • Presence of an HPV-related cervical lesion within 5-24 months prior to Day 0. This lesion will be defined alternatively as:
  • Pap test: LSIL, ASC-US.
  • Colposcopic impression suggestive of a low-grade lesion.
Show all 10Show fewer
  • Histologic report of a colposcopic biopsy consistent with a low-grade lesion.
  • Previous HPV vaccination (latest dose at least 24 months earlier than Day 0)
  • Patients able to accept and sign informed consent for the study
  • Patients able to adhere to the proposed study protocol

Who cannot join

  • High grade cervical lesions (HSIL)
  • Ongoing pregnancy, evaluated through a rapid chromatographic immunoassay for qualitative detection of hCG in urine
  • Ongoing breastfeeding
  • Primary or secondary immunodepression due to pharmacological treatments
  • No HPV vaccination
  • Daily assumption of other products containing green tea
  • Hypersensitivity or allergy to the substances contained in the supplement

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Massimo Origoni, MD contact

+39 0226432759

massimo.origoni@hsr.it

Italy1 site
  • IRCCS San Raffele Hospital

    Milan, Italy, 20100

    Massimo Origoni, MD, +39 02-26432579, massimo.origoni@hsr.it

Other trials in Italy

About this study

Official title: An Interventional Study Evaluating the Effect of Epigallocatechin Gallate (EGCG), Folic Acid (FA), Vitamin B12 (B12) and Hyaluronic Acid (HA) in Affecting the DNA Integration of Human Papilloma Virus (HPV) in Women With Persistent Infection

This interventional, single-center, open-label randomized clinical study evaluates the efficacy of an oral dietary supplement (Pervistop®) in women with persistent Human Papillomavirus (HPV) infection. The supplement is a combination of four natural molecules: Epigallocatechin gallate (EGCG), folic acid (FA), vitamin B12 (B12), and hyaluronic acid (HA).The primary objective is to describe the effect of this association on HPV DNA integration into the host genome by measuring the clearance rate of viral oncoproteins E6 and E7. A total of 42 women aged 25 or older with persistent HPV infection and low-grade cervical lesions will be randomized 1:1 into two groups. The treated group will receive one tablet of Pervistop® daily for six months, while the control group will follow standard clinical practice. The study aims to determine if this nutritional intervention can counteract viral persistence.

Read the detailed description

Human Papillomavirus (HPV) is a common sexually transmitted infection that, while often regressing spontaneously, can persist. Persistent high-risk HPV infection is a major risk factor for cervical cancer because it allows viral DNA to integrate into the host genome. This integration triggers the constitutive expression of viral oncoproteins E6 and E7, which block the host's tumor suppressor genes (p53 and prb), leading to uncontrolled cell proliferation.Currently, clinical practice for low-grade lesions typically involves a surveillance approach. This study explores the use of a synergic combination of EGCG (anti-proliferative/pro-apoptotic), Vitamin B12 and Folic Acid (methylation agents), and Hyaluronic Acid (epithelial integrity) to promote viral clearance and inhibit E6/E7 expression.

Being tested
Epigallocatechin gallate (EGCG), Folic Acid (FA), Vitamin B12 (B12), and Hyaluronic Acid (HA)
Medical subject headings
Papillomavirus Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Epigallocatechin gallate (EGCG), Folic Acid (FA), Vitamin B12 (B12), and Hyaluronic Acid (HA)Dietary supplement

    Participants will self-administer one oral tablet of the dietary supplement Pervistop daily

Study groups in NCT07697196
Study groupRoleWhat they receive
Treated Group (Pervistop®)ExperimentalPatients in this group will receive the oral supplement Pervistop®. The intervention consists of 1 tablet per day for a total duration of 6 months.
Receives: Dietary Supplement: Epigallocatechin gallate (EGCG), Folic Acid (FA), Vitamin B12 (B12), and Hyaluronic Acid (HA)
Non treated groupNo interventionParticipants in this group will receive no treatment. They will follow standard clinical practice

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Rate of clearance of viral oncoproteins E6 and E7

    The percentage of participants showing a negative result for viral E6/E7 mRNA, which are key indicators of HPV DNA integration into the host genome. Analysis will be performed using the Aptima HPV assay, a transcription-mediated amplification (TMA) technique. A negative test result indicates viral clearance or loss of viral integration.

    Measured: 6 months

Secondary outcomes (2)
  1. HPV DNA Clearance Rate

    The rate of participants who test negative for high-risk HPV DNA using a multiplex PCR kit (Allplex II HPV 28 Detection). A negative result is defined as the absence of detectable high-risk HPV DNA above the analytical limit of detection

    Measured: 6 months

  2. Treatment Adherence score

    Adherence to the oral supplementation protocol evaluated through the Morisky Medication Adherence Scale (MMAS-4) questionnaire

    Measured: 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Jul 2026
  2. Study startJul 2026 (estimated)
  3. Primary completionDec 2027 (estimated)
  4. Study completionJun 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
42 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07697196
Sponsor's protocol ID
PERVISTOP_2025
Status last verified
Jun 2026
First submitted
23 Jun 2026
Last updated
13 Jul 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided: Individual participant data will not be shared to protect participant privacy and maintain data confidentiality as per institutional policy. The study data are property of the Sponsor

Publications

  • Porcaro G, Pavone-Cossut MR, Moretti S, Bilotta G, Aragona C, Unfer V. Oral Treatment with EGCG, Folic Acid, Vitamin B12, and Hyaluronic Acid Improves HPV Clearance and Counteracts Its Persistence: A Clinical Study. Int J Mol Sci. 2025 May 29;26(11):5251. doi: 10.3390/ijms26115251.

    PubMed 40508059
  • Serrano L, Lopez AC, Gonzalez SP, Palacios S, Dexeus D, Centeno-Mediavilla C, Coronado P, de la Fuente J, Lopez JA, Vanrell C, Cortes J. Efficacy of a Coriolus versicolor-Based Vaginal Gel in Women With Human Papillomavirus-Dependent Cervical Lesions: The PALOMA Study. J Low Genit Tract Dis. 2021 Apr 1;25(2):130-136. doi: 10.1097/LGT.0000000000000596.

    PubMed 33746195
  • Abate A, Munshea A, Nibret E, Alemayehu DH, Alemu A, Abdissa A, Mihret A, Abebe M, Mulu A. Persistence and clearance rates of human papillomaviruses in a cohort of women treated or not treated for cervical dysplasia in northwest Ethiopia. Sci Rep. 2025 Mar 10;15(1):8218. doi: 10.1038/s41598-025-87568-6.

    PubMed 40064999
  • Zhou SG, Wu DF, Yao H, Zhang WY, Tian FJ, Chen G, Zhang CF. REBACIN(R) inhibits E6/E7 oncogenes in clearance of human papillomavirus infection. Front Oncol. 2022 Dec 6;12:1047222. doi: 10.3389/fonc.2022.1047222. eCollection 2022.

    PubMed 36561517
  • Tinelli A, Gustapane S, Licchelli M, Coluccia AC, Panese G, Proietti S, Gambioli R. Treatment with Epigallocatechin Gallate, Folic Acid, Vitamin B12, and Hyaluronic Acid Decreases HPV Positivity in Women Attending Regional Screening in Puglia. Microorganisms. 2024 Sep 14;12(9):1897. doi: 10.3390/microorganisms12091897.

    PubMed 39338571
  • Calcagno M, Incocciati B, Di Fraia L, Unfer V. Counteracting HPV Cervical and Anal Infection through Dietary Supplementation of EGCG, Folic Acid, Vitamin B12 and Hyaluronic Acid: Clinical Case Reports. J Clin Med. 2024 Jun 19;13(12):3597. doi: 10.3390/jcm13123597.

    PubMed 38930126
  • Grandi G, Botticelli L, Fraia PD, Babalini C, Masini M, Unfer V. The Association of Four Natural Molecules-EGCG, Folic Acid, Vitamin B12, and HA-To Counteract HPV Cervical Lesions: A Case Report. J Pers Med. 2023 Mar 22;13(3):567. doi: 10.3390/jpm13030567.

    PubMed 36983748
  • Aragona C, Bezerra Espinola MS, Bilotta G, Porcaro G, Calcagno M. Evaluating the Efficacy of Pervistop(R), a New Combination Based on EGCG, Folic Acid, Vitamin B12 and Hyaluronic Acid on Patients with Human Papilloma Virus (HPV) Persistent Infections and Cervical Lesions: A Pilot Study. J Clin Med. 2023 Mar 10;12(6):2171. doi: 10.3390/jcm12062171.

    PubMed 36983172
  • Cullen AP, Reid R, Campion M, Lorincz AT. Analysis of the physical state of different human papillomavirus DNAs in intraepithelial and invasive cervical neoplasm. J Virol. 1991 Feb;65(2):606-12. doi: 10.1128/JVI.65.2.606-612.1991.

    PubMed 1846186
  • Pirami L, Giache V, Becciolini A. Analysis of HPV16, 18, 31, and 35 DNA in pre-invasive and invasive lesions of the uterine cervix. J Clin Pathol. 1997 Jul;50(7):600-4. doi: 10.1136/jcp.50.7.600.

    PubMed 9306943
  • Pal A, Kundu R. Human Papillomavirus E6 and E7: The Cervical Cancer Hallmarks and Targets for Therapy. Front Microbiol. 2020 Jan 21;10:3116. doi: 10.3389/fmicb.2019.03116. eCollection 2019.

    PubMed 32038557
  • Giuliano AR, Nyitray AG, Kreimer AR, Pierce Campbell CM, Goodman MT, Sudenga SL, Monsonego J, Franceschi S. EUROGIN 2014 roadmap: differences in human papillomavirus infection natural history, transmission and human papillomavirus-related cancer incidence by gender and anatomic site of infection. Int J Cancer. 2015 Jun 15;136(12):2752-60. doi: 10.1002/ijc.29082. Epub 2014 Jul 26.

    PubMed 25043222
  • de Sanjose S, Serrano B, Castellsague X, Brotons M, Munoz J, Bruni L, Bosch FX. Human papillomavirus (HPV) and related cancers in the Global Alliance for Vaccines and Immunization (GAVI) countries. A WHO/ICO HPV Information Centre Report. Vaccine. 2012 Nov 20;30 Suppl 4:D1-83, vi. doi: 10.1016/S0264-410X(12)01435-1. No abstract available.

    PubMed 23510764
  • McLaughlin-Drubin ME, Munger K. Oncogenic activities of human papillomaviruses. Virus Res. 2009 Aug;143(2):195-208. doi: 10.1016/j.virusres.2009.06.008. Epub 2009 Jun 18.

    PubMed 19540281
  • Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021 May;71(3):209-249. doi: 10.3322/caac.21660. Epub 2021 Feb 4.

    PubMed 33538338

Questions about this trial

What is this clinical trial studying?

A study testing Epigallocatechin gallate (EGCG), Folic Acid (FA), Vitamin B12 (B12), and Hyaluronic Acid (HA) in people with HPV Infection and HPV Integration, run by IRCCS San Raffaele at 1 site in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: opening soon, as of the sponsor's last update on 13 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Massimo Origoni, MD (+39 0226432759, massimo.origoni@hsr.it), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Rate of clearance of viral oncoproteins E6 and E7 (time frame: 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07697196, which also lists 20 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jul 2026; AzTrials last refreshed its copy on 8 Nov 2026.

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