@article{oai:nagasaki-u.repo.nii.ac.jp:00026271,
 author = {Sumiyoshi, Remi and Koga, Tomohiro and Shimizu, Toshimasa and Sato, Shuntaro and Tashiro, Shigeki and Hosogaya, Naoki and Yamamoto, Hiroshi and Kawakami, Atsushi},
 issue = {50},
 journal = {Medicine},
 month = {Dec},
 note = {BACKGROUND: Glucocorticoids are an important class of medication for patients with adult-onset Still disease (AOSD), however, relapse following glucocorticoid reduction and adverse events due to long-term effects of glucocorticoid are still problematic. It is of course essential to minimize the risk of treatment. Immunosuppressive therapies such as methotrexate and biologics including tocilizumab are used in glucocorticoid-dependent patients with AOSD, but no second-line treatments for patients with glucocorticoid dependence have been established yet. Given that these drugs also have the potential to cause adverse events, alternative treatments are sought. Recently, elevated heme oxygenase-1 (HO-1) has been reported in the serum of patients with AOSD, suggesting that HO-1 activity contributes to AOSD pathogenesis and may represent a new therapeutic target for the treatment of AOSD. The amino acid 5-aminolevulinic acid (5-ALA) is a non-proteinogenic δ amino acid in human body. An addition of ferrous iron to 5-ALA enhances heme biosynthesis. The increase in heme in vivo induces HO-1 production, a heme-degrading enzyme. Elevated HO-1 has been suggested to contribute to the pathogenesis of AOSD, and administration of 5-ALA and ferrous iron may be a potential treatment for AOSD. METHODS/DESIGN: This study is a single-arm, open-label pilot intervention study using clinical endpoints to investigate the effects of oral 5-ALA with sodium ferrous citrate on glucocorticoid reduction in patients with AOSD receiving glucocorticoid therapy. DISCUSSION: This pilot intervention study will provide evidence regarding the effectiveness and safety of 5-ALA/sodium ferrous citrate as a potential new therapeutic agent for glucocorticoid-dependent patients with AOSD. TRIAL REGISTRATION: This study was registered in the Japan Registry of Clinical Trials (https://jrct.niph.go.jp) on January 14, 2020 as jRCTs071190042., Medicine, 99(50), e22708; 2020},
 title = {Single-arm, open-label pilot intervention study to investigate an effect of oral 5-aminolevulinic acid plus sodium ferrous citrate on glucocorticoid reduction in patients with adult-onset Still disease},
 volume = {99},
 year = {2020}
}