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

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.

Conflict of interest statement

We have the following competing interests: Y.C.P., M.H.S. are employees of and/or shareholders of Bioleaders Corporation which provided funding for this study. Bioleaders Corporation is developing γ-PGA product for cervical intraepithelial neoplasia. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors.

Figures

Fig 1. Flow diagram of the study.
Fig 1. Flow diagram of the study.

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