Short-term clinical and immunologic effects of poly-gamma-glutamic acid (γ-PGA) in women with cervical intraepithelial neoplasia 1 (CIN 1): A multicenter, randomized, double blind, phase II trial

Hyun-Woong Cho; Young-Chul Park; Moon-Hee Sung; Jong Sup Park; Tae Jin Kim; Seok Ju Seong; Chi Heum Cho; Jae Kwan Lee

doi:10.1371/journal.pone.0217745

Short-term clinical and immunologic effects of poly-gamma-glutamic acid (γ-PGA) in women with cervical intraepithelial neoplasia 1 (CIN 1): A multicenter, randomized, double blind, phase II trial

PLoS One. 2019 Jun 20;14(6):e0217745. doi: 10.1371/journal.pone.0217745. eCollection 2019.

Authors

Hyun-Woong Cho¹, Young-Chul Park², Moon-Hee Sung^{2

3}, Jong Sup Park⁴, Tae Jin Kim⁵, Seok Ju Seong⁶, Chi Heum Cho⁷, Jae Kwan Lee¹

Affiliations

¹ Department of Obstetrics and Gynecology, Guro Hospital, College of Medicine, Korea University, Seoul, Korea.
² Bioleaders Corporation, Daejeon, Korea.
³ Department of Bio and Fermentation Convergence Technology, Kookmin University, Seoul, Korea.
⁴ Department of Obstetrics and Gynecology, Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea.
⁵ Department of Obstetrics and Gynecology, Konkuk University School of Medicine, Seoul, Korea.
⁶ Department of Obstetrics and Gynecology, CHA Gangnam Medical Center, CHA University, Seoul, Korea.
⁷ Department of Obstetrics and Gynecology, Keimyung University Dongsan Medical Center, Daegu, Korea.

Abstract

Objective: The aim of this study was to investigate the short-term efficacy and safety of Poly-gamma-glutamic acid (γ-PGA) and the immunologic changes in patients with CIN 1.

Methods: Participants were randomly assigned to one of two groups and orally treated with placebo or 1,500 mg of γ-PGA for 4 weeks. The primary endpoint of the study was histologic regression rate of CIN 1 at 12 weeks between γ-PGA and control groups. The secondary endpoints were HPV clearance and change in immune responses.

Result: From April 2013 to December 2015, 195 patients participated in the study. In the intention-to-treat analysis, 42 (42.4%) of the women who received γ-PGA experienced histologic remission versus 26 (27.1%) in the control group, with a statistically significant difference (p = 0.018). In the γ-PGA group, HPV clearance was found in 37 (43.5%) of 85 patients infected with high-risk HPV, showing a significant difference compared to the control group, in which 20 (26.7%) of 75 patients exhibited HPV clearance (p = 0.026). However, there was no significant difference between the two groups in the change of NK cell activity, major histocompatibility complex (MHC) class II CD8 count, and CD56 count.

Conclusion: γ-PGA showed a short-term therapeutic effect on CIN 1 and high-risk HPV infection. It is a non-invasive, promising oral medication for women with these conditions.

Trial registration: Clinical Trials NCT01826045.

Publication types

Clinical Trial, Phase II
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Double-Blind Method
Female
Humans
Killer Cells, Natural / immunology
Placebos
Polyglutamic Acid / analogs & derivatives*
Polyglutamic Acid / pharmacology
Uterine Cervical Dysplasia / drug therapy*
Uterine Cervical Dysplasia / immunology*

Substances

Placebos
poly(gamma-glutamic acid)
Polyglutamic Acid

Associated data

ClinicalTrials.gov/NCT01826045

Grants and funding

This study received funding from Bioleaders Corporation. The funder provided support in the form of salaries for authors [Y.C.P., M.H.S.]. This research also was financially supported by the Ministry of Trade, Industry, and Energy (MOTIE), Korea, under the “Leading Industry Development for Economic Region (R&D, R0001832)” supervised by the Korea Institute for Advancement of Technology (KIAT). This trial was designed by authors including Y.C.P., M.H.S.. However, Y.C.P., M.H.S. did not have any additional role in the data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.