Research Article: 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

Date Published: June 20, 2019

Publisher: Public Library of Science

Author(s): Hyun-Woong Cho, Young-Chul Park, Moon-Hee Sung, Jong Sup Park, Tae Jin Kim, Seok Ju Seong, Chi Heum Cho, Jae Kwan Lee, Jung Ryeol Lee.

http://doi.org/10.1371/journal.pone.0217745

Abstract

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.

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.

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.

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.

Clinical Trials NCT01826045.

Partial Text

Cervical intraepithelial neoplasia (CIN) can be a precursor to invasive cervical cancer and is the most common significant gynecologic disease in women of reproductive age [1]. In general, conservative management is recommended for patients with CIN 1 because they are considered to have a transient HPV infection, and the condition spontaneously regresses within 2 years in more than 60% of cases [2–4]. However, 16–30% of patients had persistent low-grade lesion and 4–10% progressed to high-grade lesion. If the disease is persistent or progressive, invasive procedures may be required [2, 5–7]. In addition, most patients want more active treatment because repeated follow-up tests are stressful and can negatively affect the patient’s daily life [8]. Therefore, development of a new agent to treat CIN 1 is necessary.

The study was carried out according to the principles expressed in the Declaration of Helsinki and Korean good clinical practice (KGCP). The study received institutional review board (IRB) of Korea university guro hospital (2013GR0058) and was registered as clinicaltrials.gov study NCT01826045. Each subject gave written consent for their participation. The Protocol for this Trial and supporting CONSORT checklist are available as supporting information (S1 Text, S2 Text and S1 Table).

From April 2013 to December 2015, 195 subjects meeting inclusion criteria were enrolled from six medical centers in Korea (Fig 1). Forty-seven women did not meet the inclusion criteria, seven refused to participate, and five did not appear at the baseline visit. A total of 195 baseline surveys were conducted. During the study, 45 women were excluded: 17 for loss to follow-up and 28 for protocol violations. However, as analysis was based on the ITT principle, all excluded subjects were included in the final analysis.

Our data suggest that γ-PGA is efficacious in promoting histologic regression and clearance of high-risk HPV in patients with CIN 1 in the short term. To our knowledge, γ-PGA is the only oral medication proven to be efficacious for regression of CIN I and clearance of high-risk HPV in a randomized controlled trial (RCT). γγ-PGA is extracted from the traditional Korean food Chungkukjang and it exhibits excellent tolerability and safety.

γ-PGA showed a short-term therapeutic effect in CIN 1 and high-risk HPV infection. It is a promising new oral medication for women with CIN 1 and women with high-risk HPV infection. However, no significant effect was observed on specific HPV types, such as 16 and 18, and the immunologic response did not change with γ-PGA treatment. Therefore, further studies of the mechanism of γ-PGA activity are needed.

 

Source:

http://doi.org/10.1371/journal.pone.0217745

 

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