Title: | Open-label clinical trial of bezafibrate treatment in patients with fatty acid oxidation disorders in Japan |
Authors: | Yamada, Kenji Browse this author |
Shiraishi, Hideaki Browse this author →KAKEN DB |
Oki, Eishin Browse this author |
Ishige, Mika Browse this author |
Fukao, Toshiyuki Browse this author |
Hamada, Yusuke Browse this author |
Sakai, Norio Browse this author |
Ochi, Fumihiro Browse this author |
Watanabe, Asami Browse this author |
Kawakami, Sanae Browse this author |
Kuzume, Kazuyo Browse this author |
Watanabe, Kenji Browse this author |
Sameshima, Koji Browse this author |
Nakamagoe, Kiyotaka Browse this author |
Tamaoka, Akira Browse this author |
Asahina, Naoko Browse this author |
Yokoshiki, Saki Browse this author |
Miyakoshi, Takashi Browse this author |
Ono, Kota Browse this author |
Oba, Koji Browse this author →KAKEN DB |
Isoe, Toshiyuki Browse this author |
Hayashi, Hiroshi Browse this author |
Yamaguchi, Seiji Browse this author |
Sato, Norihiro Browse this author |
Keywords: | Bezafibrate |
Fatty acid oxidation disorders (FAODs) |
Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency |
Carnitine palmitoyltransferase-II (CPT-2) deficiency |
Clinical trial |
Issue Date: | Jun-2018 |
Publisher: | Elsevier |
Journal Title: | Molecular genetics and metabolism reports |
Volume: | 15 |
Start Page: | 55 |
End Page: | 63 |
Publisher DOI: | 10.1016/j.ymgmr.2018.02.003 |
Abstract: | Introduction: Fatty acid oxidation disorders (FAODs) are rare diseases caused by defects in mitochondrial fatty acid oxidation (FAO) enzymes. While the efficacy of bezafibrate, a peroxisome proliferator-activated receptor agonist, on the in vitro FAO capacity has been reported, the in vivo efficacy remains controversial. Therefore, we conducted a clinical trial of bezafibrate in Japanese patients with FAODs. Materials and methods: This trial was an open-label, non-randomized, and multicenter study of bezafibrate treatment in 6 patients with very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency and 2 patients with carnitine palmitoyltransferase-II (CPT-2) deficiency (median age, 8.2 years; ranging from 5.8 to 26.4 years). Bezafibrate was administered for 6 months following a 6-month observation period. The primary endpoint was the frequency of myopathic attacks, and the secondary endpoints were serum acylcarnitines (ACs, C14:1 or C16 + C18:1), creatine kinase (CK) levels, degree of muscle pain (VAS; visual analog scale) during myopathic attacks, and quality of life (QOL; evaluated using validated questionnaires). Results: The frequency of myopathic attacks after bezafibrate administration decreased in 3 patients, increased in 3, and did not change in 2. The CK, AC, and VAS values during attacks could be estimated in only three or four patients, but a half of the patients did not experience attacks before or after treatment. Changes in CK, AC, and VAS values varied across individuals. In contrast, three components of QOL, namely, physical functioning, role limitation due to physical problems (role physical), and social functioning, were significantly elevated. No adverse drug reactions were observed. Conclusion: In this study, the frequency of myopathic attacks and CK, AC, and VAS values during the attacks could not be evaluated due to several limitations, such as a small trial population. Our findings indicate that bezafibrate improves the QOL of patients with FAODs, but its efficacy must be examined in future investigations. |
Rights: | http://creativecommons.org/licenses/by/4.0/ |
Type: | article |
URI: | http://hdl.handle.net/2115/71201 |
Appears in Collections: | 北海道大学病院 (Hokkaido University Hospital) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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