Protocol for a Randomized, Open-Label Clinical Trial on the Effect of Mouthwash on Salivary SARS-CoV-2 Load

Keiji Konishi; Daisuke Onozuka; Satoko Takatera; Hiroo Matsuo; Hisao Yoshida; Shigeto Hamaguchi; Shungo Yamamoto; Ryuichi Minoda Sada; Koichiro Suzuki; Satoshi Kutsuna

doi:10.3390/life13122312

Protocol for a Randomized, Open-Label Clinical Trial on the Effect of Mouthwash on Salivary SARS-CoV-2 Load

Life (Basel). 2023 Dec 8;13(12):2312. doi: 10.3390/life13122312.

Authors

Keiji Konishi^{1

2}, Daisuke Onozuka^{1

2}, Satoko Takatera^{1

2}, Hiroo Matsuo², Hisao Yoshida², Shigeto Hamaguchi^{2

3

4}, Shungo Yamamoto^{2

4

5}, Ryuichi Minoda Sada^{2

4

5}, Koichiro Suzuki⁶, Satoshi Kutsuna^{1

2

3

4

5}

Affiliations

¹ Department of Oral Microbe Control, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan.
² Department of Infection Control and Prevention, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan.
³ Department of Transformative Analysis for Human Specimen, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan.
⁴ Division of Fostering Required Medical Human Resources, Center for Infectious Disease Education and Research (CiDER), Osaka University, Osaka 565-0871, Japan.
⁵ Department of Transformative Protection to Infectious Disease, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan.
⁶ The Research Foundation for Microbial Diseases of Osaka University (BIKEN), Osaka 565-0871, Japan.

Abstract

Mouthwashes containing cetylpyridinium chloride (CPC) or on-demand aqueous chlorine dioxide (ACD) have potential to reduce the salivary severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) load in individuals with SARS-CoV-2 infection. This study will evaluate the effect of CPC and on-demand ACD mouthwashes on salivary SARS-CoV-2 levels in individuals with acute asymptomatic or mild SARS-CoV-2 infection (COVID-19) staying in a residential recuperation facility in Osaka, Japan. This randomized, open-label clinical trial will include three equal-sized groups (CPC mouthwash, on-demand ACD mouthwash, and placebo), with 30 participants per group. A stratified replacement block method will be used to ensure balanced allocation based on symptom presence and days since symptom onset. Participants will use mouthwash at set times for 7 days or until the end of recuperation. Saliva samples will be collected at multiple time points and tested for SARS-CoV-2 using quantitative reverse transcription polymerase chain reaction. The primary outcome will be changes in salivary SARS-CoV-2 viral load 2 h after the first mouthwash use compared with the pre-mouthwash level. Secondary outcomes will include changes in salivary viral load and clinical parameters at different time points. This study was registered with the Japan Registry of Clinical Trials on 18 October 2022 (jRCTs051220107).

Keywords: COVID-19; SARS-CoV-2; cetylpyridinium chloride; mouthwash; on-demand aqueous chlorine dioxide solution; open-label randomized clinical trial.

Grants and funding

This study is supported by the Earth Corporation, Tokyo, Japan. The funder has no role in the design or conduct of the trial and is not involved in the collection or analysis of the data, in the writing of the manuscript, or in making the decision to submit the manuscript for publication.