Atsushi Hashizume1, Masahisa Katsuno2, Keisuke Suzuki1,3, Haruhiko Banno1, Yu Takeuchi1, Motoshi Kawashima1, Noriaki Suga1, Tomoo Mano1, Amane Araki1, Yasuhiro Hijikata1, Akihiro Hirakawa4, Gen Sobue5,6. 1. Department of Neurology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, showa-ku, Nagoya, Aichi, 466-8550, Japan. 2. Department of Neurology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, showa-ku, Nagoya, Aichi, 466-8550, Japan. ka2no@med.nagoya-u.ac.jp. 3. Department of Clinical Research, Innovation Center for Clinical Research, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan. 4. Department of Biostatistics and bioinformatics, The University of Tokyo, Graduate school of Medicine, Tokyo, Japan. 5. Department of Neurology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, showa-ku, Nagoya, Aichi, 466-8550, Japan. sobueg@med.nagoya-u.ac.jp. 6. Research Division of Dementia and Neurodegenerative Disease, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, showa-ku, Nagoya, 466-8550, Japan. sobueg@med.nagoya-u.ac.jp.
Abstract
BACKGROUND: Spinal and bulbar muscular atrophy (SBMA) is an adult-onset, hereditary neuromuscular disease characterized by muscle atrophy, weakness, contraction fasciculation, and bulbar involvement. Although the causative gene, androgen receptor, has been identified, the development of novel therapeutics for SBMA is incomplete. In this study, the efficacy and safety of leuprorelin acetate administration for patients with SBMA, using the pooled data of two randomized-controlled trials, was studied. METHODS: Two randomized double-blinded studies (JASMITT-06DB and JASMITT-11DB) were done as multicentric, investigator-initiated clinical trials in Japan. In both studies, eligible patients were randomly assigned 1:1 to receive leuprorelin acetate administration once per 12 weeks for 48 weeks. The primary endpoint was the longitudinal change of pharyngeal barium residues from the baseline data measured with videofluorographic swallowing analyses. The pooled analysis plan was decided upon after the 06B study was finished and before the 11DB study began. RESULTS: The primary endpoint difference between the leuprorelin group and the placebo group was pharyngeal barium residue after initial swallowing, - 4.12% (95% CI, - 8.40-0.15; p = 0.058). The primary endpoint of this study does not reach significant results, although inter-group differences of pharyngeal barium residues after the initial swallowing indicated that leuprorelin acetate may be effective at each assessment point in both study groups. CONCLUSIONS: The efficacy of leuprorelin acetate for patients with SBMA was statistically similar in two randomized-controlled trials, and suggested that leuprorelin acetate may be effective and safe. Further investigations are needed to clarify the promising efficacy of the drug.
RCT Entities:
BACKGROUND:Spinal and bulbar muscular atrophy (SBMA) is an adult-onset, hereditary neuromuscular disease characterized by muscle atrophy, weakness, contraction fasciculation, and bulbar involvement. Although the causative gene, androgen receptor, has been identified, the development of novel therapeutics for SBMA is incomplete. In this study, the efficacy and safety of leuprorelin acetate administration for patients with SBMA, using the pooled data of two randomized-controlled trials, was studied. METHODS: Two randomized double-blinded studies (JASMITT-06DB and JASMITT-11DB) were done as multicentric, investigator-initiated clinical trials in Japan. In both studies, eligible patients were randomly assigned 1:1 to receive leuprorelin acetate administration once per 12 weeks for 48 weeks. The primary endpoint was the longitudinal change of pharyngeal barium residues from the baseline data measured with videofluorographic swallowing analyses. The pooled analysis plan was decided upon after the 06B study was finished and before the 11DB study began. RESULTS: The primary endpoint difference between the leuprorelin group and the placebo group was pharyngeal barium residue after initial swallowing, - 4.12% (95% CI, - 8.40-0.15; p = 0.058). The primary endpoint of this study does not reach significant results, although inter-group differences of pharyngeal barium residues after the initial swallowing indicated that leuprorelin acetate may be effective at each assessment point in both study groups. CONCLUSIONS: The efficacy of leuprorelin acetate for patients with SBMA was statistically similar in two randomized-controlled trials, and suggested that leuprorelin acetate may be effective and safe. Further investigations are needed to clarify the promising efficacy of the drug.
Entities:
Keywords:
Clinical trial; Disease-modifying therapy; Leuprorelin acetate; Motor neuron disease; Spinal and bulbar muscular atrophy
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