Safety and efficacy of 5-aminolevulinic acid phosphate/iron in mild-to-moderate coronavirus disease 2019: A randomized exploratory phase II trial

Author:

Tanaka Takeshi1ORCID,Tashiro Masato12,Ota Kenji3,Fujita Ayumi1,Sawai Toyomitsu4,Kadota Junichi4,Fukuda Yuichi5,Sumiyoshi Makoto6,Ide Shotaro6,Tachikawa Natsuo7,Fujii Hiroshi8,Hibino Makoto9,Shiomi Hisanori10,Izumida Mai11,Matsui Kohsuke11,Yamauchi Momoko11,Takahashi Kensuke11,Yamanashi Hirotomo1112,Sugimoto Takashi11,Akabame Shogo12,Umeda Masataka12,Shimizu Masumi11,Hosogaya Naoki13,Kosai Kosuke3,Takeda Kazuaki14,Iwanaga Naoki14,Ashizawa Nobuyuki114,Hirayama Tatsuro14,Takazono Takahiro214,Yamamoto Kazuko14,Imamura Yoshifumi14,Miyazaki Taiga14,Kobayashi Yusuke15,Ariyoshi Koya11,Mukae Hiroshi1416,Yanagihara Katsunori3,Kita Kiyoshi1718,Izumikawa Koichi12

Affiliation:

1. Infection Control and Education Center, Nagasaki University Hospital, Nagasaki-shi, Nagasaki, Japan

2. Department of Infectious Diseases, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki-shi, Nagasaki, Japan

3. Department of Laboratory Medicine, Nagasaki University Hospital, Nagasaki-shi, Nagasaki, Japan

4. Department of Respiratory Medicine, Nagasaki Harbor Medical Center, Nagasaki-shi, Nagasaki, Japan

5. Department of Respiratory Medicine, Sasebo City General Hospital, Sasebo-shi, Nagasaki, Japan

6. Department of Respiratory Medicine, Isahaya General Hospital, Japan Community Health Care Organization, Isahaya-shi, Nagasaki, Japan

7. Department of Infectious Diseases, Yokohama Municipal Citizen’s Hospital, Yokohama-shi, Kanagawa, Japan

8. Department of Respiratory Medicine, Kobe City Medical Center West Hospital, Kobe-shi, Hyogo, Japan

9. Department of Respiratory Medicine, Shonan Fujisawa Tokushukai Hospital, Fujisawa-shi, Kanagawa, Japan

10. Department of Surgery, Nagahama Red Cross Hospital, Nagahama-shi, Shiga, Japan

11. Department of Infectious Diseases, Nagasaki University Hospital, Nagasaki-shi, Nagasaki, Japan

12. Department of General Medicine, Nagasaki University Hospital, Nagasaki-shi, Nagasaki, Japan

13. Clinical Research Center, Nagasaki University Hospital, Nagasaki-shi, Nagasaki, Japan

14. Department of Respiratory Medicine, Nagasaki University Hospital, Nagasaki-shi, Nagasaki, Japan

15. Clinical Development Department, Neopharma Japan Co. Ltd., Chiyoda-ku, Tokyo, Japan

16. Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki-shi, Nagasaki, Japan

17. School of Tropical Medicine and Global Health, Nagasaki University, Nagasaki-shi, Nagasaki, Japan

18. Department of Host-Defense Biochemistry, Institute of Tropical Medicine Nagasaki University, Nagasaki-shi, Nagasaki, Japan.

Abstract

Background:5-aminolevulinic acid (5-ALA), a natural amino acid that is marketed alongside sodium ferrous citrate (SFC) as a functional food, blocks severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) proliferation in vitro and exerts anti-inflammatory effects. In this phase II open-label, prospective, parallel-group, randomized trial, we aimed to evaluate the safety and efficacy of 5-ALA in patients with mild-to-moderate coronavirus disease 2019.Methods:This trial was conducted in patients receiving 5-ALA/SFC (250/145 mg) orally thrice daily for 7 days, followed by 5-ALA/SFC (150/87 mg) orally thrice daily for 7 days. The primary endpoints were changes in SARS-CoV-2 viral load, clinical symptom scores, and 5-ALA/SFC safety (adverse events [AE] and changes in laboratory values and vital signs).Results:A total of 50 patients were enrolled from 8 institutions in Japan. The change in SARS-CoV-2 viral load from baseline was not significantly different between the 5-ALA/SFC (n = 24) and control (n = 26) groups. The duration to improvement was shorter in the 5-ALA/SFC group than in the control group, although the difference was not significant. The 5-ALA/SFC group exhibited faster improvement rates in “taste abnormality,” “cough,” “lethargy,” and “no appetite” than the control group. Eight AEs were observed in the 5-ALA/SFC group, with 22.7% of patients experiencing gastrointestinal symptoms (decreased appetite, constipation, and vomiting). AEs occurred with 750/435 mg/day in 25.0% of patients in the first phase and with 450/261 mg/day of 5-ALA/SFC in 6.3% of patients in the second phase.Conclusion:5-ALA/SFC improved some symptoms but did not influence the SARS-CoV-2 viral load or clinical symptom scores over 14 days. The safety of 5-ALA/SFC in this study was acceptable. Further evaluation using a larger sample size or modified method is warranted.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

General Medicine

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