Effect of EGCG, Folic Acid, Vitamin B12 and Hyaluronic Acid on HPV DNA Integration
2026年7月6日 更新者：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.
研究概览
地位
尚未招聘
条件
详细说明
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.
研究类型
介入性
注册 (估计的)
42
阶段
- 不适用
联系人和位置
本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。
学习联系方式
- 姓名：Massimo Origoni, MD
- 电话号码：+39 0226432759
- 邮箱：massimo.origoni@hsr.it
学习地点
-
-
Italy
-
Milan、Italy、意大利、20100
- IRCCS San Raffele Hospital
-
接触：
- Massimo Origoni, MD
- 电话号码：+39 02-26432579
- 邮箱：massimo.origoni@hsr.it
-
-
参与标准
研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
- 成人
- 年长者
接受健康志愿者
不
描述
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
学习计划
本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：随机化
- 介入模型：并行分配
- 屏蔽：无（打开标签）
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
|
实验性的：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
|
|
无干预：Non treated group
Participants in this group will receive no treatment.
They will follow standard clinical practice
|
研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Rate of clearance of viral oncoproteins E6 and E7
大体时间：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
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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HPV DNA Clearance Rate
大体时间：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
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Treatment Adherence score
大体时间：6 months
|
Adherence to the oral supplementation protocol evaluated through the Morisky Medication Adherence Scale (MMAS-4) questionnaire
|
6 months
|
其他结果措施
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Quantitative Variation of E6/E7 Levels from baseline to T1
大体时间：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
|
合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
出版物和有用的链接
负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。
一般刊物
- 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.
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始 (估计的)
2026年7月1日
初级完成 (估计的)
2027年12月1日
研究完成 (估计的)
2028年6月1日
研究注册日期
首次提交
2026年6月23日
首先提交符合 QC 标准的
2026年7月6日
首次发布 (实际的)
2026年7月13日
研究记录更新
最后更新发布 (实际的)
2026年7月13日
上次提交的符合 QC 标准的更新
2026年7月6日
最后验证
2026年6月1日
更多信息
与本研究相关的术语
其他相关的 MeSH 术语
其他研究编号
- PERVISTOP_2025
计划个人参与者数据 (IPD)
计划共享个人参与者数据 (IPD)？
未定
IPD 计划说明
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
药物和器械信息、研究文件
研究美国 FDA 监管的药品
不
研究美国 FDA 监管的设备产品
不
此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.