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Yamada K, Shiraishi H, Oki E, et al. Open-label clinical trial of bezafibrate treatment in patients with fatty acid oxidation disorders in Japan. Mol Genet Metab Rep. 2018;15:55-63doi: 10.1016/j.ymgmr.2018.02.003.
Yamada, K., Shiraishi, H., Oki, E., Ishige, M., Fukao, T., Hamada, Y., Sakai, N., Ochi, F., Watanabe, A., Kawakami, S., Kuzume, K., Watanabe, K., Sameshima, K., Nakamagoe, K., Tamaoka, A., Asahina, N., Yokoshiki, S., Miyakoshi, T., Ono, K., Oba, K., Isoe, T., Hayashi, H., Yamaguchi, S., & Sato, N. (2018). Open-label clinical trial of bezafibrate treatment in patients with fatty acid oxidation disorders in Japan. Molecular genetics and metabolism reports, 1555-63. https://doi.org/10.1016/j.ymgmr.2018.02.003
Yamada, Kenji, et al. "Open-label clinical trial of bezafibrate treatment in patients with fatty acid oxidation disorders in Japan." Molecular genetics and metabolism reports vol. 15 (2018): 55-63. doi: https://doi.org/10.1016/j.ymgmr.2018.02.003
Yamada K, Shiraishi H, Oki E, Ishige M, Fukao T, Hamada Y, Sakai N, Ochi F, Watanabe A, Kawakami S, Kuzume K, Watanabe K, Sameshima K, Nakamagoe K, Tamaoka A, Asahina N, Yokoshiki S, Miyakoshi T, Ono K, Oba K, Isoe T, Hayashi H, Yamaguchi S, Sato N. Open-label clinical trial of bezafibrate treatment in patients with fatty acid oxidation disorders in Japan. Mol Genet Metab Rep. 2018 Feb 22;15:55-63. doi: 10.1016/j.ymgmr.2018.02.003. eCollection 2018 Jun. PMID: 29552494; PMCID: PMC5852296.
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Mol Genet Metab Rep. 2018 Feb 22;15:55-63. doi: 10.1016/j.ymgmr.2018.02.003. eCollection 2018 Jun.

Open-label clinical trial of bezafibrate treatment in patients with fatty acid oxidation disorders in Japan.

Molecular genetics and metabolism reports

Kenji Yamada, Hideaki Shiraishi, Eishin Oki, Mika Ishige, Toshiyuki Fukao, Yusuke Hamada, Norio Sakai, Fumihiro Ochi, Asami Watanabe, Sanae Kawakami, Kazuyo Kuzume, Kenji Watanabe, Koji Sameshima, Kiyotaka Nakamagoe, Akira Tamaoka, Naoko Asahina, Saki Yokoshiki, Takashi Miyakoshi, Kota Ono, Koji Oba, Toshiyuki Isoe, Hiroshi Hayashi, Seiji Yamaguchi, Norihiro Sato

Affiliations

  1. Department of Pediatrics, Shimane University Faculty of Medicine, 89-1, En-ya-cho, Izumo, Shimane 693-8501, Japan.
  2. Department of Pediatrics, Hokkaido University School of Medicine, Kita 15, Nishi 7, Kita-ku, Sapporo 060-8638, Japan.
  3. Department of Pediatrics, Tsugaru General Hospital, 12-3, Iwaki-cho, Goshogawara, Aomori 037-0074, Japan.
  4. Department of Pediatrics and Child Health, Nihon University School of Medicine, 1-6, Kanda-Surugadai, Chiyoda-ku, Tokyo 101-8309, Japan.
  5. Department of Pediatrics, Graduate School of Medicine, Gifu University, 1-1, Yanagito, Gifu 501-1194, Japan.
  6. Department of Pediatrics, Osaka University Faculty of Medicine, 2-2, Yamadaoka, Suita, Osaka 565-0871, Japan.
  7. Department of Pediatrics, Osaka Hospital, Japan Community Healthcare Organization, 4-2-78, Fukushima, Fukushima-ku, Osaka 553-0003, Japan.
  8. Department of Pediatrics, Yawatahama City General Hospital, 638, Ohira-ichibankochi, Yawatahama, Ehime 796-8502, Japan.
  9. Department of Pediatrics, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime 791-0295, Japan.
  10. Department of Community and Emergency Medicine, Ehime University School of Medicine, Shitsukawa, Toon, Ehime 791-0295, Japan.
  11. Department of Pediatrics, Kagoshima City Hospital, 37-1, Uearata-cho, Kagoshima 890-8760, Japan.
  12. Department of Neurology, Division of Clinical Medicine, Faculty of Medicine, University of Tsukuba, 1-1-1, Tennoudai, Tsukuba, Ibaraki 305-8575, Japan.
  13. Hokkaido University Hospital Clinical Research and Medical Innovation Center, Research and Development Division, Kita 14, Nishi 5, Kita-ku, Sapporo 060-8648, Japan.
  14. Hokkaido University Hospital Clinical Research and Medical Innovation Center, Biostatistics Division, Kita 14, Nishi 5, Kita-ku, Sapporo 060-8648, Japan.
  15. Department of Biostatistics, School of Public Health, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
  16. Hokkaido University Hospital Clinical Research and Medical Innovation Center, Kita 14, Nishi 5, Kita-ku, Sapporo 060-8648, Japan.

PMID: 29552494 PMCID: PMC5852296 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

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.

Keywords: Bezafibrate; Carnitine palmitoyltransferase-II (CPT-2) deficiency; Clinical trial; Fatty acid oxidation disorders (FAODs); Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency

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