Efficacy of Lactococcus lactis strain plasma (LC-Plasma) in easing symptoms in patients with mild coronavirus disease 2019 (COVID-19): protocol for an exploratory, multicenter, double-blinded, randomized controlled trial (PLATEAU study)
Authors: Yamamoto Kazuko , Hosogaya Naoki , Inoue Tsuyoshi , Jounai Kenta , Tsuji Ryohei , Fujiwara Daisuke , Yanagihara Katsunori , Izumikawa Koichi , Mukae Hiroshi 
Published: February 2022

ABSTRACTIntroductionThe coronavirus disease 2019 (COVID-19) pandemic has been a major concern worldwide; however, easily accessible treatment options for patients with mild COVID-19 remains limited. Since oral intake of Lactococcus lactis strain Plasma (LC-Plasma) enhances both the innate and acquired immune systems through activation of plasmacytoid dendritic cells (pDCs), we hypothesized that the oral intake of LC-Plasma could aid the relief or prevention of symptoms in patients with asymptomatic or mild COVID-19.Methods and analysisThis is an exploratory, multicenter, double-blind, randomized, placebo-controlled trial. This study was initiated in December 2021 and concludes in April 2023. The planned number of enrolled subjects is 100 (50 patients × 2 groups); subject enrolment will be conducted until October 2022. Patients with asymptomatic or mild COVID-19 will be enrolled and randomly assigned in a 1:1 ratio to Group A (oral intake of LC-Plasma-containing capsule, 200 mg/day, for 14 days) or Group B (oral intake of placebo capsule, for 14 days). The primary endpoint is the change in subjective symptoms measured by the severity score. Secondary endpoints include SARS-CoV-2 viral loads, biomarkers for pDC activation, serum SARS-CoV-2-specific antibodies, serum cytokines, interferon and interferon-inducible antiviral effectors, and the proportion of subjects with emergency room visits to medical institutions or who are hospitalized.Ethics and disseminationThe study protocol was approved by the Clinical Research Review Board of Nagasaki University, in accordance with the Clinical Trials Act of Japan. The study will be conducted in accordance with the Declaration of Helsinki, Clinical Trials Act, and other current legal regulations in Japan. Written informed consent will be obtained from all participants. The results of this study will be reported in journal publications.RegistrationThis study was registered in the Japan Registry of Clinical Trials (registration number: jRCTs071210097).ARTICLE SUMMARYStrengths and limitations of this studyThis is the first randomized controlled trial to assess the efficacy of Lactococcus lactis strain Plasma (LC-Plasma) in preventing the onset and attenuation of symptoms in patients with asymptomatic or mild COVID-19.This study is also the first to evaluate the significance of pDC-related immune responses, including interferon production, clearance of symptoms, and prevention of COVID-19 progression.The results of this study may contribute to the development of novel treatment options for asymptomatic or mild COVID-19 patients.This is an exploratory study, due to the lack of previous clinical evidence that evaluated the effect of LC-Plasma intake in patients with COVID-19.Other limitations include the subjective endpoint as the primary endpoint and generalizability, since this study will be conducted only in Japan in Japanese patients.