Effect of EGCG, Folic Acid, Vitamin B12 and Hyaluronic Acid on HPV DNA Integration
6 juli 2026 bijgewerkt door: Massimo Origoni, IRCCS San Raffaele
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.
Studie Overzicht
Toestand
Nog niet aan het werven
Conditie
Gedetailleerde beschrijving
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.
Studietype
Ingrijpend
Inschrijving (Geschat)
42
Fase
- Niet toepasbaar
Contacten en locaties
In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.
Studiecontact
- Naam: Massimo Origoni, MD
- Telefoonnummer: +39 0226432759
- E-mail: massimo.origoni@hsr.it
Studie Locaties
-
-
Italy
-
Milan, Italy, Italië, 20100
- IRCCS San Raffele Hospital
-
Contact:
- Massimo Origoni, MD
- Telefoonnummer: +39 02-26432579
- E-mail: massimo.origoni@hsr.it
-
-
Deelname Criteria
Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
- Volwassen
- Oudere volwassene
Accepteert gezonde vrijwilligers
Nee
Beschrijving
Inclusion Criteria:
- 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.
- 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
Exclusion Criteria:
- 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
Studie plan
Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: Gerandomiseerd
- Interventioneel model: Parallelle opdracht
- Masker: Geen (open label)
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
|---|---|
|
Experimenteel: Treated Group (Pervistop®)
Patients in this group will receive the oral supplement Pervistop®.
The intervention consists of 1 tablet per day for a total duration of 6 months.
|
Participants will self-administer one oral tablet of the dietary supplement Pervistop daily
|
|
Geen tussenkomst: Non treated group
Participants in this group will receive no treatment.
They will follow standard clinical practice
|
Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
|
Rate of clearance of viral oncoproteins E6 and E7
Tijdsspanne: 6 months
|
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.
|
6 months
|
Secundaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
|
HPV DNA Clearance Rate
Tijdsspanne: 6 months
|
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
|
6 months
|
|
Treatment Adherence score
Tijdsspanne: 6 months
|
Adherence to the oral supplementation protocol evaluated through the Morisky Medication Adherence Scale (MMAS-4) questionnaire
|
6 months
|
Andere uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
|
Quantitative Variation of E6/E7 Levels from baseline to T1
Tijdsspanne: 6 months
|
Variation of E6/E7 mRNA levels.
Exploratory analysis of quantitative signals generated by the Aptima assay in the form of Relative Luminescent Units (RLU).
The RLU value directly corresponds to the amount of target E6/E7 mRNA detected in the sample.
|
6 months
|
Medewerkers en onderzoekers
Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.
Sponsor
Publicaties en nuttige links
De persoon die verantwoordelijk is voor het invoeren van informatie over het onderzoek stelt deze publicaties vrijwillig ter beschikking. Dit kan gaan over alles wat met het onderzoek te maken heeft.
Algemene publicaties
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Qiao Y, Cao J, Xie L, Shi X. Cell growth inhibition and gene expression regulation by (-)-epigallocatechin-3-gallate in human cervical cancer cells. Arch Pharm Res. 2009 Sep;32(9):1309-15. doi: 10.1007/s12272-009-1917-3. Epub 2009 Sep 26.
- Xiao S, Jia H, Guo Y, Ding X, Zheng A. Chemoprophylactic Effects of Epigallocatechin Gallate in Female Reproductive Cancers - A Review. J Diet Suppl. 2025;22(4):487-510. doi: 10.1080/19390211.2025.2518409. Epub 2025 Jun 15.
- Yap JKW, Kehoe ST, Woodman CBJ, Dawson CW. The Major Constituent of Green Tea, Epigallocatechin-3-Gallate (EGCG), Inhibits the Growth of HPV18-Infected Keratinocytes by Stimulating Proteasomal Turnover of the E6 and E7 Oncoproteins. Pathogens. 2021 Apr 11;10(4):459. doi: 10.3390/pathogens10040459.
- Frega A, Gentili C, Proietti S, Lepore E, Unfer V, Fuso A. Epigallocatechin gallate, folic acid, vitamin B12, and hyaluronic acid significantly increase apoptosis and p53 expression in HeLa cells. Eur Rev Med Pharmacol Sci. 2023 Jun;27(11):5240-5245. doi: 10.26355/eurrev_202306_32642.
- Aarthy M, Panwar U, Singh SK. Structural dynamic studies on identification of EGCG analogues for the inhibition of Human Papillomavirus E7. Sci Rep. 2020 May 26;10(1):8661. doi: 10.1038/s41598-020-65446-7.
Studie record data
Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.
Bestudeer belangrijke data
Studie start (Geschat)
1 juli 2026
Primaire voltooiing (Geschat)
1 december 2027
Studie voltooiing (Geschat)
1 juni 2028
Studieregistratiedata
Eerst ingediend
23 juni 2026
Eerst ingediend dat voldeed aan de QC-criteria
6 juli 2026
Eerst geplaatst (Werkelijk)
13 juli 2026
Updates van studierecords
Laatste update geplaatst (Werkelijk)
13 juli 2026
Laatste update ingediend die voldeed aan QC-criteria
6 juli 2026
Laatst geverifieerd
1 juni 2026
Meer informatie
Termen gerelateerd aan deze studie
Aanvullende relevante MeSH-voorwaarden
- Urogenitale ziekten
- Genitale ziekten
- Pathologische processen
- Ziekte attributen
- Infecties
- Virusziekten
- Overdraagbare ziekten
- Seksueel overdraagbare aandoeningen, viraal
- Seksueel overdraagbare aandoeningen
- DNA-virusinfecties
- Tumorvirusinfecties
- Pathologische aandoeningen, tekenen en symptomen
- Papillomavirus-infecties
- Heterocyclische verbindingen, 1-ring
- Heterocyclische verbindingen
- Heterocyclische verbindingen, 2-ring
- Heterocyclische verbindingen, gefuseerd ring
- Azoles
- Koolhydraten
- Polycyclische verbindingen
- Pterins
- Pteridines
- Glycosaminoglycans
- Polysachariden
- Heterocyclische verbindingen, 4 of meer ringen
- Pyrroles
- Macrocyclische verbindingen
- Tetrapyrroles
- Corrinoïden
- Foliumzuur
- Hyaluronzuur
- Vitamine B12
- epigallocatechin gallate
Andere studie-ID-nummers
- PERVISTOP_2025
Plan Individuele Deelnemersgegevens (IPD)
Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?
ONBESLIST
Beschrijving IPD-plan
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
Informatie over medicijnen en apparaten, studiedocumenten
Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel
Nee
Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct
Nee
Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .