Effect of EGCG, Folic Acid, Vitamin B12 and Hyaluronic Acid on HPV DNA Integration
6 juli 2026 uppdaterad av: 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.
Studieöversikt
Status
Har inte rekryterat ännu
Betingelser
Detaljerad beskrivning
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.
Studietyp
Interventionell
Inskrivning (Beräknad)
42
Fas
- Inte tillämpbar
Kontakter och platser
Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.
Studiekontakt
- Namn: Massimo Origoni, MD
- Telefonnummer: +39 0226432759
- E-post: massimo.origoni@hsr.it
Studieorter
-
-
Italy
-
Milan, Italy, Italien, 20100
- IRCCS San Raffele Hospital
-
Kontakt:
- Massimo Origoni, MD
- Telefonnummer: +39 02-26432579
- E-post: massimo.origoni@hsr.it
-
-
Deltagandekriterier
Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.
Urvalskriterier
Åldrar som är berättigade till studier
- Vuxen
- Äldre vuxen
Tar emot friska volontärer
Nej
Beskrivning
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
Studieplan
Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.
Hur är studien utformad?
Designdetaljer
- Primärt syfte: Behandling
- Tilldelning: Randomiserad
- Interventionsmodell: Parallellt uppdrag
- Maskning: Ingen (Open Label)
Vapen och interventioner
Deltagargrupp / Arm |
Intervention / Behandling |
|---|---|
|
Experimentell: 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
|
|
Inget ingripande: Non treated group
Participants in this group will receive no treatment.
They will follow standard clinical practice
|
Vad mäter studien?
Primära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
|
Rate of clearance of viral oncoproteins E6 and E7
Tidsram: 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
|
Sekundära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
|
HPV DNA Clearance Rate
Tidsram: 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
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6 months
|
|
Treatment Adherence score
Tidsram: 6 months
|
Adherence to the oral supplementation protocol evaluated through the Morisky Medication Adherence Scale (MMAS-4) questionnaire
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6 months
|
Andra resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
|
Quantitative Variation of E6/E7 Levels from baseline to T1
Tidsram: 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
|
Samarbetspartners och utredare
Det är här du hittar personer och organisationer som är involverade i denna studie.
Sponsor
Publikationer och användbara länkar
Den som ansvarar för att lägga in information om studien tillhandahåller frivilligt dessa publikationer. Dessa kan handla om allt som har med studien att göra.
Allmänna publikationer
- 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.
Studieavstämningsdatum
Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.
Studera stora datum
Studiestart (Beräknad)
1 juli 2026
Primärt slutförande (Beräknad)
1 december 2027
Avslutad studie (Beräknad)
1 juni 2028
Studieregistreringsdatum
Först inskickad
23 juni 2026
Först inskickad som uppfyllde QC-kriterierna
6 juli 2026
Första postat (Faktisk)
13 juli 2026
Uppdateringar av studier
Senaste uppdatering publicerad (Faktisk)
13 juli 2026
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
6 juli 2026
Senast verifierad
1 juni 2026
Mer information
Termer relaterade till denna studie
Ytterligare relevanta MeSH-villkor
- Urogenitala sjukdomar
- Genitala sjukdomar
- Patologiska processer
- Sjukdomsegenskaper
- Infektioner
- Virussjukdomar
- Smittsamma sjukdomar
- Sexuellt överförbara sjukdomar, virala
- Sexuellt överförbara sjukdomar
- DNA-virusinfektioner
- Tumörvirusinfektioner
- Patologiska tillstånd, tecken och symtom
- Papillomavirusinfektioner
- Heterocykliska föreningar, 1-ring
- Heterocykliska föreningar
- Heterocykliska föreningar, 2-ring
- Heterocykliska föreningar, smältring
- Azoler
- Kolhydrater
- Polycykliska föreningar
- Pteriner
- Pteridiner
- Glykosaminoglykaner
- Polysackarider
- Heterocykliska föreningar, 4 eller fler ringar
- Pyrrol
- Makrocykliska föreningar
- Tetrapyrrol
- Korinoider
- Folsyra
- Hyaluronsyra
- Vitamin B 12
- epigallocatechin gallera
Andra studie-ID-nummer
- PERVISTOP_2025
Plan för individuella deltagardata (IPD)
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OBESLUTSAM
IPD-planbeskrivning
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
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