Efficacy of tranilast in preventing exacerbating cardiac function and death from heart failure in muscular dystrophy patients with advanced-stage heart failure: a single-arm, open-label, multicenter study
Abstract Background Transient receptor potential cation channel subfamily V member 2 (TRPV2) functions as a stretch-sensitive calcium channel, with overexpression in the sarcolemma of skeletal and cardiac myocytes leading to detrimental calcium influx and triggering muscle degeneration. In our previ...
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BMC
2025-01-01
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| Series: | Orphanet Journal of Rare Diseases |
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| Online Access: | https://doi.org/10.1186/s13023-025-03538-1 |
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| author | Tsuyoshi Matsumura Takayasu Fukudome Yasufumi Motoyoshi Akinori Nakamura Satoshi Kuru Kazuhiko Segawa Ruriko Kitao Chigusa Watanabe Takuhisa Tamura Toshiaki Takahashi Hiroya Hashimoto Masahiro Sekimizu Akiko M. Saito Masanori Asakura Koichi Kimura Yuko Iwata |
| author_facet | Tsuyoshi Matsumura Takayasu Fukudome Yasufumi Motoyoshi Akinori Nakamura Satoshi Kuru Kazuhiko Segawa Ruriko Kitao Chigusa Watanabe Takuhisa Tamura Toshiaki Takahashi Hiroya Hashimoto Masahiro Sekimizu Akiko M. Saito Masanori Asakura Koichi Kimura Yuko Iwata |
| author_sort | Tsuyoshi Matsumura |
| collection | DOAJ |
| description | Abstract Background Transient receptor potential cation channel subfamily V member 2 (TRPV2) functions as a stretch-sensitive calcium channel, with overexpression in the sarcolemma of skeletal and cardiac myocytes leading to detrimental calcium influx and triggering muscle degeneration. In our previous pilot study, we showed that tranilast, a TRPV2 inhibitor, reduced brain natriuretic peptide levels in two patients with muscular dystrophy and advanced heart failure. Building on this, we performed a single-arm, open-label, multicenter study herein to evaluate the safety and efficacy of tranilast in the treatment of advanced heart failure in patients with muscular dystrophy. Results This study involved 18 patients with muscular dystrophy who had brain natriuretic peptide levels > 100 pg/mL, despite receiving standard cardioprotective therapy. Tranilast was administered orally at a dose of 100 mg three times daily. Over the short-term period (28 weeks), the primary endpoint of change ratio in the logarithm of brain natriuretic peptide level from baseline to 28 weeks was not significant in the full analysis set but was lower in the per set protocol compared with data from a previous beta-blocker treatment study. All 15 patients who completed the short-term treatment consented to be enrolled in long-term therapy for an additional 116 weeks. After all participants completed the long-term treatment, we analyzed all data. TRPV2 expression on the peripheral blood mononuclear cell surfaces decreased throughout the study period, confirming that the TRPV2 inhibitory effect of tranilast was maintained over time. Despite the presence of progressive disease, cardiac indices such as brain natriuretic peptide level, human atrial natriuretic peptide level, and fractional shortening, remained stable, and only brain natriuretic peptide levels at 144 weeks showed significant changes. The survival rate was 80.7%, and no cardiac deaths were reported. Regarding safety, no serious adverse events associated with tranilast were noted, except for recurrent diarrhea during the short-term period in one case. Conclusions The findings suggest that tranilast can inhibit TRPV2 expression for an extended period and is effective in preventing the worsening of cardiac function and subsequent death from heart failure. Clinical trial registration details The study was registered in the UMIN Clinical Trials Registry (UMIN-CTR: UMIN000031965, URL: http://www.umin.ac.jp/ctr/ ) [March 30, 2018] and the Japan Registry of Clinical Trials (jRCT, registration number: jRCTs031180038, URL: https://jrct.niph.go.jp/ ) [November 12, 2021]. Patient registration was initiated on December 19, 2018. |
| format | Article |
| id | doaj-art-0e222fd3a62d4c838c48844a73709a58 |
| institution | Kabale University |
| issn | 1750-1172 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
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| series | Orphanet Journal of Rare Diseases |
| spelling | doaj-art-0e222fd3a62d4c838c48844a73709a582025-01-12T12:39:35ZengBMCOrphanet Journal of Rare Diseases1750-11722025-01-012011910.1186/s13023-025-03538-1Efficacy of tranilast in preventing exacerbating cardiac function and death from heart failure in muscular dystrophy patients with advanced-stage heart failure: a single-arm, open-label, multicenter studyTsuyoshi Matsumura0Takayasu Fukudome1Yasufumi Motoyoshi2Akinori Nakamura3Satoshi Kuru4Kazuhiko Segawa5Ruriko Kitao6Chigusa Watanabe7Takuhisa Tamura8Toshiaki Takahashi9Hiroya Hashimoto10Masahiro Sekimizu11Akiko M. Saito12Masanori Asakura13Koichi Kimura14Yuko Iwata15Department of Neurology, NHO Osaka Toneyama Medical CenterDepartment of Neurology, NHO Nagasaki Kawatana Medical CenterDepartment of Neurology, NHO Shimoshizu National HospitalDepartment of Clinical Research, NHO Matsumoto Medical CenterDepartment of Neurology, NHO Suzuka HospitalDepartment of Cardiology, National Center of Neurology and PsychiatryDepartment of Neurology, NHO Hakone HospitalDepartment of Neurology, NHO Hiroshima-Nishi Medical CenterDepartment of Neurology, NHO Higashisaitama HospitalDepartment of Neurology, NHO Sendai Nishitaga HospitalClinical Research Center, NHO Nagoya Medical CenterClinical Research Center, NHO Nagoya Medical CenterClinical Research Center, NHO Nagoya Medical CenterDepartment of Clinical Diagnosis and Laboratory Medicine, Hyogo College of MedicineDepartment of Laboratory Medicine/Cardiology, The Institute of Medical Science, The University of TokyoDepartment of Cardiac Physiology, National Cerebral and Cardiovascular Center Research InstituteAbstract Background Transient receptor potential cation channel subfamily V member 2 (TRPV2) functions as a stretch-sensitive calcium channel, with overexpression in the sarcolemma of skeletal and cardiac myocytes leading to detrimental calcium influx and triggering muscle degeneration. In our previous pilot study, we showed that tranilast, a TRPV2 inhibitor, reduced brain natriuretic peptide levels in two patients with muscular dystrophy and advanced heart failure. Building on this, we performed a single-arm, open-label, multicenter study herein to evaluate the safety and efficacy of tranilast in the treatment of advanced heart failure in patients with muscular dystrophy. Results This study involved 18 patients with muscular dystrophy who had brain natriuretic peptide levels > 100 pg/mL, despite receiving standard cardioprotective therapy. Tranilast was administered orally at a dose of 100 mg three times daily. Over the short-term period (28 weeks), the primary endpoint of change ratio in the logarithm of brain natriuretic peptide level from baseline to 28 weeks was not significant in the full analysis set but was lower in the per set protocol compared with data from a previous beta-blocker treatment study. All 15 patients who completed the short-term treatment consented to be enrolled in long-term therapy for an additional 116 weeks. After all participants completed the long-term treatment, we analyzed all data. TRPV2 expression on the peripheral blood mononuclear cell surfaces decreased throughout the study period, confirming that the TRPV2 inhibitory effect of tranilast was maintained over time. Despite the presence of progressive disease, cardiac indices such as brain natriuretic peptide level, human atrial natriuretic peptide level, and fractional shortening, remained stable, and only brain natriuretic peptide levels at 144 weeks showed significant changes. The survival rate was 80.7%, and no cardiac deaths were reported. Regarding safety, no serious adverse events associated with tranilast were noted, except for recurrent diarrhea during the short-term period in one case. Conclusions The findings suggest that tranilast can inhibit TRPV2 expression for an extended period and is effective in preventing the worsening of cardiac function and subsequent death from heart failure. Clinical trial registration details The study was registered in the UMIN Clinical Trials Registry (UMIN-CTR: UMIN000031965, URL: http://www.umin.ac.jp/ctr/ ) [March 30, 2018] and the Japan Registry of Clinical Trials (jRCT, registration number: jRCTs031180038, URL: https://jrct.niph.go.jp/ ) [November 12, 2021]. Patient registration was initiated on December 19, 2018.https://doi.org/10.1186/s13023-025-03538-1Transient receptor potential cation channel subfamily V member 2Muscular dystrophyHeart failureCardiac eventTranilast |
| spellingShingle | Tsuyoshi Matsumura Takayasu Fukudome Yasufumi Motoyoshi Akinori Nakamura Satoshi Kuru Kazuhiko Segawa Ruriko Kitao Chigusa Watanabe Takuhisa Tamura Toshiaki Takahashi Hiroya Hashimoto Masahiro Sekimizu Akiko M. Saito Masanori Asakura Koichi Kimura Yuko Iwata Efficacy of tranilast in preventing exacerbating cardiac function and death from heart failure in muscular dystrophy patients with advanced-stage heart failure: a single-arm, open-label, multicenter study Orphanet Journal of Rare Diseases Transient receptor potential cation channel subfamily V member 2 Muscular dystrophy Heart failure Cardiac event Tranilast |
| title | Efficacy of tranilast in preventing exacerbating cardiac function and death from heart failure in muscular dystrophy patients with advanced-stage heart failure: a single-arm, open-label, multicenter study |
| title_full | Efficacy of tranilast in preventing exacerbating cardiac function and death from heart failure in muscular dystrophy patients with advanced-stage heart failure: a single-arm, open-label, multicenter study |
| title_fullStr | Efficacy of tranilast in preventing exacerbating cardiac function and death from heart failure in muscular dystrophy patients with advanced-stage heart failure: a single-arm, open-label, multicenter study |
| title_full_unstemmed | Efficacy of tranilast in preventing exacerbating cardiac function and death from heart failure in muscular dystrophy patients with advanced-stage heart failure: a single-arm, open-label, multicenter study |
| title_short | Efficacy of tranilast in preventing exacerbating cardiac function and death from heart failure in muscular dystrophy patients with advanced-stage heart failure: a single-arm, open-label, multicenter study |
| title_sort | efficacy of tranilast in preventing exacerbating cardiac function and death from heart failure in muscular dystrophy patients with advanced stage heart failure a single arm open label multicenter study |
| topic | Transient receptor potential cation channel subfamily V member 2 Muscular dystrophy Heart failure Cardiac event Tranilast |
| url | https://doi.org/10.1186/s13023-025-03538-1 |
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