NCT07344337 — Evaluation of the Effect of a Dietary Supplement Based on EGCG, Vitamin B12, Hyaluronic Acid, and Folic Acid on the Maintenance of Physiological Balance and the Natural Defenses of the Male Genital System in Subjects Exposed to HPV Infection. · CancerIndex
Clinical trial · Interventional
Evaluation of the Effect of a Dietary Supplement Based on EGCG, Vitamin B12, Hyaluronic Acid, and Folic Acid on the Maintenance of Physiological Balance and the Natural Defenses of the Male Genital System in Subjects Exposed to HPV Infection.
This is a randomized pilot interventional study aimed at evaluating the effect of a dietary supplement containing EGCG, vitamin B12, hyaluronic acid, and folic acid on the maintenance of physiological balance and natural defenses of the male genital tract in subjects exposed to HPV infection and seeking care for infertility at natural procreation centers. The study includes 48 couples (96 participants) recruited at the International Scientific Institute "Paolo VI" of the A. Gemelli Policlinico, randomly assigned to two groups: 24 couples in which both partners receive one oral tablet per day of the supplement for 6 months, and 24 control couples receiving no supplementation. In addition to the primary objective, secondary outcomes assess potential support of sperm parameters, reproductive well-being of the couples, maintenance of genital mucosal physiological balance with possible reduction of HPV transmission risk to female partners, and support of physiological balance in the presence of co-infections or alterations of the genital microbiota.
Conditions
Conditions (2)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
Condition (as posted)
Mapped entity
Match
Confidence
HPV Infection
—
UNRESOLVED
—
Infertilities
—
UNRESOLVED
—
Interventions
Interventions (1)
Intervention
Type
Mapped drug
Match
Pervistop
Dietary Supplement
—
UNRESOLVED
Design
Arms and outcomes
Arms (2)
type
EXPERIMENTAL
label
Patients taking Pervistop
description
24 couples in which both partners will be treated with a combination of EGCG (200 mg), vitamin B12 (1 mg), hyaluronic acid (50 mg), and folic acid (400 µg), administered orally as one tablet once daily for 6 months.
interventionNames
Dietary Supplement: Pervistop
type
NO_INTERVENTION
label
Patients NO taking Pervistop
description
24 couples who will not receive any supplementation
Primary outcomes (1)
measure
The aim of the study is to evaluate the effect of a combination of EGCG, vitamin B12, hyaluronic acid, and folic acid on the maintenance of physiological balance and natural defense mechanisms of the male genital tract in subjects who, due to infertility
timeFrame
From enrollment to the end of treatment at 6 months
Eligibility
Eligibility (as posted)
Sex
All
Minimum age
25 Years
Maximum age
65 Years
Show eligibility criteria text
Inclusion Criteria:
* Signed informed consent
* Couple seeking pregnancy
* Male partner aged 25-65 years
* HPV DNA test indicating active HPV infection in the male partner
* HPV DNA test indicating negativity for HPV infection in the female partner
Exclusion Criteria:
* Concomitant diseases causing immunosuppression
* Treatment with immunomodulatory therapies
* Use of EGCG or other green tea extracts
References
Publications (41)
BACKGROUNDOno A, Koshiyama M, Nakagawa M, Watanabe Y, Ikuta E, Seki K, Oowaki M. The Preventive Effect of Dietary Antioxidants on Cervical Cancer Development. Medicina (Kaunas). 2020 Nov 10;56(11):604. doi: 10.3390/medicina56110604. PMID 33182663
BACKGROUNDZhang D, Wen X, Wu W, Guo Y, Cui W. Elevated homocysteine level and folate deficiency associated with increased overall risk of carcinogenesis: meta-analysis of 83 case-control studies involving 35,758 individuals. PLoS One. 2015 May 18;10(5):e0123423. doi: 10.1371/journal.pone.0123423. eCollection 2015. PMID 25985325
BACKGROUNDAhn WS, Yoo J, Huh SW, Kim CK, Lee JM, Namkoong SE, Bae SM, Lee IP. Protective effects of green tea extracts (polyphenon E and EGCG) on human cervical lesions. Eur J Cancer Prev. 2003 Oct;12(5):383-90. doi: 10.1097/00008469-200310000-00007. PMID 14512803
RESULTWeinberg M, Sar-Shalom Nahshon C, Feferkorn I, Bornstein J. Evaluation of human papilloma virus in semen as a risk factor for low sperm quality and poor in vitro fertilization outcomes: a systematic review and meta-analysis. Fertil Steril. 2020 May;113(5):955-969.e4. doi: 10.1016/j.fertnstert.2020.01.010. PMID 32386620
RESULTPorcaro 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. PMID 40508059
RESULTTinelli 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. PMID 39338571
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.
description
The aim is to ensure continued HPV test negativity in the male partner throughout the six-month course of Pervistop therapy. The presence of the viral genotype will be determined by urethral swab sampling, followed by gene amplification using polymerase chain reaction (PCR) methodology.
RESULTKwanbunjan K., Saengkar P., Cheeramakara C., Thanomsak W., Benjachai W.,Laisupasin P., Buchachart K., Songmuaeng K., Boontaveeyuwat N. Low folate status as a risk factor for cervical dysplasia in Thai women. Nutr. Res. 2005;25:641-654. doi: 10.1016/j.nutres.2005.05.004.
RESULTHernandez BY, McDuffie K, Wilkens LR, Kamemoto L, Goodman MT. Diet and premalignant lesions of the cervix: evidence of a protective role for folate, riboflavin, thiamin, and vitamin B12. Cancer Causes Control. 2003 Nov;14(9):859-70. doi: 10.1023/b:caco.0000003841.54413.98. PMID 14682443
RESULTPiyathilake CJ, Henao OL, Macaluso M, Cornwell PE, Meleth S, Heimburger DC, Partridge EE. Folate is associated with the natural history of high-risk human papillomaviruses. Cancer Res. 2004 Dec 1;64(23):8788-93. doi: 10.1158/0008-5472.CAN-04-2402. PMID 15574793
RESULTPiyathilake CJ, Macaluso M, Chambers MM, Badiga S, Siddiqui NR, Bell WC, Edberg JC, Partridge EE, Alvarez RD, Johanning GL. Folate and vitamin B12 may play a critical role in lowering the HPV 16 methylation-associated risk of developing higher grades of CIN. Cancer Prev Res (Phila). 2014 Nov;7(11):1128-37. doi: 10.1158/1940-6207.CAPR-14-0143. Epub 2014 Aug 21. PMID 25145486
RESULTSedjo RL, Inserra P, Abrahamsen M, Harris RB, Roe DJ, Baldwin S, Giuliano AR. Human papillomavirus persistence and nutrients involved in the methylation pathway among a cohort of young women. Cancer Epidemiol Biomarkers Prev. 2002 Apr;11(4):353-9. PMID 11927495
RESULTYap 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. PMID 33920477
RESULTZou C, Liu H, Feugang JM, Hao Z, Chow HH, Garcia F. Green tea compound in chemoprevention of cervical cancer. Int J Gynecol Cancer. 2010 May;20(4):617-24. doi: 10.1111/IGC.0b013e3181c7ca5c. PMID 20686382
RESULTChu C, Deng J, Man Y, Qu Y. Green Tea Extracts Epigallocatechin-3-gallate for Different Treatments. Biomed Res Int. 2017;2017:5615647. doi: 10.1155/2017/5615647. Epub 2017 Aug 13. PMID 28884125
RESULTTzellos TG, Sardeli C, Lallas A, Papazisis G, Chourdakis M, Kouvelas D. Efficacy, safety and tolerability of green tea catechins in the treatment of external anogenital warts: a systematic review and meta-analysis. J Eur Acad Dermatol Venereol. 2011 Mar;25(3):345-53. doi: 10.1111/j.1468-3083.2010.03796.x. PMID 21294779
RESULTTatti S, Swinehart JM, Thielert C, Tawfik H, Mescheder A, Beutner KR. Sinecatechins, a defined green tea extract, in the treatment of external anogenital warts: a randomized controlled trial. Obstet Gynecol. 2008 Jun;111(6):1371-9. doi: 10.1097/AOG.0b013e3181719b60. PMID 18515521
RESULTStockfleth E, Beti H, Orasan R, Grigorian F, Mescheder A, Tawfik H, Thielert C. Topical Polyphenon E in the treatment of external genital and perianal warts: a randomized controlled trial. Br J Dermatol. 2008 Jun;158(6):1329-38. doi: 10.1111/j.1365-2133.2008.08520.x. Epub 2008 Mar 20. PMID 18363746
RESULTGross G, Meyer KG, Pres H, Thielert C, Tawfik H, Mescheder A. A randomized, double-blind, four-arm parallel-group, placebo-controlled Phase II/III study to investigate the clinical efficacy of two galenic formulations of Polyphenon E in the treatment of external genital warts. J Eur Acad Dermatol Venereol. 2007 Nov;21(10):1404-12. doi: 10.1111/j.1468-3083.2007.02441.x. PMID 17958849
RESULTFiorillo L, Cervino G, Surace G, De Stefano R, Laino L, D'Amico C, Fiorillo MT, Meto A, Herford AS, Arzukanyan AV, Spagnuolo G, Cicciu M. Human Papilloma Virus: Current Knowledge and Focus on Oral Health. Biomed Res Int. 2021 Feb 1;2021:6631757. doi: 10.1155/2021/6631757. eCollection 2021. PMID 33623784
RESULTPal 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. PMID 32038557
RESULTKato Y, Shigehara K, Nakagawa T, Nakata H, Iijima M, Nakashima K, Kawaguchi S, Izumi K, Kadono Y, Mizokami A. Human papillomavirus detected in sperm of Japanese infertile males affects reproductive parameters. Int J Infect Dis. 2021 Nov;112:294-299. doi: 10.1016/j.ijid.2021.09.029. Epub 2021 Sep 20. PMID 34547493
RESULTSchillaci R, Capra G, Bellavia C, Ruvolo G, Scazzone C, Venezia R, Perino A. Detection of oncogenic human papillomavirus genotypes on spermatozoa from male partners of infertile couples. Fertil Steril. 2013 Nov;100(5):1236-40. doi: 10.1016/j.fertnstert.2013.06.042. Epub 2013 Jul 24. PMID 23891022
RESULTDe Toni L, Muscianisi F, Corsini C, Ghezzi M, Di Nisio A, Foresta C, Garolla A. Serum Anti-HPV Antibody Titer as a Marker of Vaccine Effectiveness in Males with Genital Infection. Vaccines (Basel). 2020 Dec 7;8(4):743. doi: 10.3390/vaccines8040743. PMID 33297367
RESULTForesta C, Noventa M, De Toni L, Gizzo S, Garolla A. HPV-DNA sperm infection and infertility: from a systematic literature review to a possible clinical management proposal. Andrology. 2015 Mar;3(2):163-73. doi: 10.1111/andr.284. Epub 2014 Oct 1. PMID 25270519
RESULTForesta C, Garolla A, Zuccarello D, Pizzol D, Moretti A, Barzon L, Palu G. Human papillomavirus found in sperm head of young adult males affects the progressive motility. Fertil Steril. 2010 Feb;93(3):802-6. doi: 10.1016/j.fertnstert.2008.10.050. Epub 2008 Dec 18. PMID 19100537
RESULTLenzi A, Mirone V, Gentile V, Bartoletti R, Ficarra V, Foresta C, Mariani L, Mazzoli S, Parisi SG, Perino A, Picardo M, Zotti CM. Rome Consensus Conference - statement; human papilloma virus diseases in males. BMC Public Health. 2013 Feb 7;13:117. doi: 10.1186/1471-2458-13-117. PMID 23391351
RESULTLaprise C, Trottier H, Monnier P, Coutlee F, Mayrand MH. Prevalence of human papillomaviruses in semen: a systematic review and meta-analysis. Hum Reprod. 2014 Apr;29(4):640-51. doi: 10.1093/humrep/det453. Epub 2013 Dec 22. PMID 24365799
RESULTPerez-Andino J, Buck CB, Ribbeck K. Adsorption of human papillomavirus 16 to live human sperm. PLoS One. 2009 Jun 9;4(6):e5847. doi: 10.1371/journal.pone.0005847. PMID 19513123
RESULTZacharis K, Messini CI, Anifandis G, Koukoulis G, Satra M, Daponte A. Human Papilloma Virus (HPV) and Fertilization: A Mini Review. Medicina (Kaunas). 2018 Jul 27;54(4):50. doi: 10.3390/medicina54040050. PMID 30344281
RESULTGarolla A, Engl B, Pizzol D, Ghezzi M, Bertoldo A, Bottacin A, Noventa M, Foresta C. Spontaneous fertility and in vitro fertilization outcome: new evidence of human papillomavirus sperm infection. Fertil Steril. 2016 Jan;105(1):65-72.e1. doi: 10.1016/j.fertnstert.2015.09.018. Epub 2015 Oct 9. PMID 26453270
RESULTLorenzon L, Terrenato I, Dona MG, Ronchetti L, Rollo F, Marandino F, Carosi M, Diodoro MG, Sentinelli S, Visca P, Vocaturo G, Bellardini P, Vocaturo A, Benevolo M. Prevalence of HPV infection among clinically healthy Italian males and genotype concordance between stable sexual partners. J Clin Virol. 2014 Jul;60(3):264-9. doi: 10.1016/j.jcv.2014.04.003. Epub 2014 Apr 15. PMID 24794396
RESULTKero K, Rautava J. HPV Infections in Heterosexual Couples: Mechanisms and Covariates of Virus Transmission. Acta Cytol. 2019;63(2):143-147. doi: 10.1159/000494710. Epub 2019 Feb 22. PMID 30799413
RESULTWiddice L, Ma Y, Jonte J, Farhat S, Breland D, Shiboski S, Moscicki AB. Concordance and transmission of human papillomavirus within heterosexual couples observed over short intervals. J Infect Dis. 2013 Apr 15;207(8):1286-94. doi: 10.1093/infdis/jit018. Epub 2013 Jan 14. PMID 23319742
RESULTGiuliano 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. PMID 25043222
RESULTde 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. PMID 23510764
RESULTDoorbar J, Quint W, Banks L, Bravo IG, Stoler M, Broker TR, Stanley MA. The biology and life-cycle of human papillomaviruses. Vaccine. 2012 Nov 20;30 Suppl 5:F55-70. doi: 10.1016/j.vaccine.2012.06.083. PMID 23199966
RESULTCid Arregui A, Gariglio P, Kanda T, Doorbar J. ONCOGENIC HUMAN PAPILLOMAVIRUSES: High-Risk Human Papillomaviruses: Towards a Better Understanding of the Mechanisms of Viral Transformation, Latency and Immune-Escape. Open Virol J. 2012;6:160-2. doi: 10.2174/1874357901206010160. Epub 2012 Dec 28. No abstract available. PMID 23346264
RESULTMcLaughlin-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. PMID 19540281
RESULTBosch FX, Broker TR, Forman D, Moscicki AB, Gillison ML, Doorbar J, Stern PL, Stanley M, Arbyn M, Poljak M, Cuzick J, Castle PE, Schiller JT, Markowitz LE, Fisher WA, Canfell K, Denny LA, Franco EL, Steben M, Kane MA, Schiffman M, Meijer CJ, Sankaranarayanan R, Castellsagué X, Kim JJ, Brotons M, Alemany L, Albero G, Diaz M, de Sanjosé S; ICO Monograph 'Comprehensive Control of HPV Infections and Related Diseases' Vaccine Volume 30, Supplement 5, 2012. Comprehensive control of human papillomavirus infections and related diseases. Vaccine. 2013 Dec 30;31 Suppl 6:G1-31. doi: 10.1016/j.vaccine.2013.10.002. PMID: 24331817.
RESULTSung 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. PMID 33538338