The Experts below are selected from a list of 93 Experts worldwide ranked by ideXlab platform
Michio Ozeki - One of the best experts on this subject based on the ideXlab platform.
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The impact of sirolimus therapy on lesion size, clinical symptoms, and quality of life of patients with Lymphatic anomalies.
Orphanet journal of rare diseases, 2019Co-Authors: Michio Ozeki, Akifumi Nozawa, Shiho Yasue, Saori Endo, Ryuta Asada, Hiroya Hashimoto, Toshiyuki FukaoAbstract:Lymphatic anomalies (LAs) include several disorders in which abnormal Lymphatic tissue invades the neck, chest, and various organs. Progressive cases may result in lethal outcomes and have proven difficult to treat. Sirolimus is showing promising results in the management of vascular anomalies. We examined the efficacy and safety of sirolimus treatment in patients with progressive LAs. All patients with LAs treated with sirolimus from May 2015 to September 2018 were included. They received oral sirolimus once a day and the dose was adjusted so that the trough concentration remained within 5–15 ng/mL. We prospectively reviewed the response to drugs (the response rate of radiological volumetric change of the target lesion), severity scores, reported quality of life (QOL), and adverse effects at 6 months after administration. Twenty patients (five with Cystic Lymphatic Malformation (LM), three with kaposiform lymphangiomatosis, three with generalized Lymphatic anomaly, six with Gorham-Stout disease, and three with central conducting Lymphatic anomaly) were treated with sirolimus at our institution. Fifty percent of patients (10/20) demonstrated a partial response by a radiological examination and a significant improvement in disease severity and QOL scores (P = 0.0020 and P = 0.0117, respectively). Ten patients who had no reduction in lesion size (stable disease group) showed no significant improvement in disease severity and QOL scores. Eighty percent of patients (16/20) had side effects, such as stomatitis, infection, and hyperlipidemia. Sirolimus impacts the reduction of the Lymphatic tissue volume of LMs and could lead to improvement in clinical symptoms and QOL. UMIN Clinical Trials Registry, UMIN000016580 . Registered 19 February 2015,
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The impact of sirolimus therapy on lesion size, clinical symptoms, and quality of life of patients with Lymphatic anomalies
Orphanet Journal of Rare Diseases, 2019Co-Authors: Michio Ozeki, Akifumi Nozawa, Shiho Yasue, Saori Endo, Ryuta Asada, Hiroya Hashimoto, Toshiyuki FukaoAbstract:Background Lymphatic anomalies (LAs) include several disorders in which abnormal Lymphatic tissue invades the neck, chest, and various organs. Progressive cases may result in lethal outcomes and have proven difficult to treat. Sirolimus is showing promising results in the management of vascular anomalies. We examined the efficacy and safety of sirolimus treatment in patients with progressive LAs. Methods All patients with LAs treated with sirolimus from May 2015 to September 2018 were included. They received oral sirolimus once a day and the dose was adjusted so that the trough concentration remained within 5–15 ng/mL. We prospectively reviewed the response to drugs (the response rate of radiological volumetric change of the target lesion), severity scores, reported quality of life (QOL), and adverse effects at 6 months after administration. Results Twenty patients (five with Cystic Lymphatic Malformation (LM), three with kaposiform lymphangiomatosis, three with generalized Lymphatic anomaly, six with Gorham-Stout disease, and three with central conducting Lymphatic anomaly) were treated with sirolimus at our institution. Fifty percent of patients (10/20) demonstrated a partial response by a radiological examination and a significant improvement in disease severity and QOL scores ( P = 0.0020 and P = 0.0117, respectively). Ten patients who had no reduction in lesion size (stable disease group) showed no significant improvement in disease severity and QOL scores. Eighty percent of patients (16/20) had side effects, such as stomatitis, infection, and hyperlipidemia. Conclusions Sirolimus impacts the reduction of the Lymphatic tissue volume of LMs and could lead to improvement in clinical symptoms and QOL. Trial registration UMIN Clinical Trials Registry, UMIN000016580 . Registered 19 February 2015,
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Efficacy and safety of sirolimus treatment for intractable Lymphatic anomalies: A study protocol for an open-label, single-arm, multicenter, prospective study (SILA)
Regenerative therapy, 2019Co-Authors: Michio Ozeki, Ryuta Asada, Hiroya Hashimoto, Takumi Fujimura, Tatsuo Kuroda, Shigeru Ueno, Shoji Watanabe, Shunsuke Nosaka, Akiko Saito, Mikiko MiyasakaAbstract:Abstract Introduction Lymphatic anomalies (LAs) refer to a group of diseases involving systemic dysplasia of Lymphatic vessels. These lesions are classified as Cystic Lymphatic Malformation (macroCystic, microCystic or mixed), generalized Lymphatic anomaly, and Gorham–Stout disease. LAs occur mainly in childhood, and present with various symptoms including chronic airway problems, recurrent infection, and organ disorders. Individuals with LAs often experience progressively worsening symptoms with a deteriorating quality of life. Although limited treatment options are available, their efficacy has not been validated in prospective clinical trials, and are usually based on case reports. Thus, there are no validated standards of care for these patients because of the lack of prospective clinical trials. Methods This open-label, single-arm, multicenter, prospective study will assess the efficacy and safety of a mammalian target of the rapamycin inhibitor sirolimus in the treatment of intractable LAs. Participants will receive oral sirolimus once a day for 52 weeks. The dose is adjusted so that the nadir concentration remains within 5–15 ng/ml. The primary endpoint is the response rate of radiological volumetric change of the target lesion confirmed by central review at 52 weeks after treatment. The secondary endpoints are the response rates at 12 and 24 weeks, respiratory function, pleural effusion, ascites, blood coagulation parameters, bleeding, pain, quality of life, activities of daily living, adverse events, side effects, laboratory examinations, vital signs, and pharmacokinetic data. Results This is among the first multicenter studies to evaluate sirolimus treatment for intractable LAs, and few studies to date have focused on the standard assessment of the efficacy for LAs treatment. Our protocol uses novel, uncomplicated methods for radiological assessment, with reference to the results of our previous retrospective survey and historical control data from the literature. Conclusions We propose a multicenter study to investigate the efficacy and safety of sirolimus for intractable LAs (SILA study; trial registration UMIN000028905). Our results will provide pivotal data to support the approval of sirolimus for the treatment of intractable LAs.
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Efficacy and safety of sirolimus treatment for intractable Lymphatic anomalies: A study protocol for an open-label, single-arm, multicenter, prospective study (SILA)
Elsevier, 2019Co-Authors: Michio Ozeki, Ryuta Asada, Hiroya Hashimoto, Akiko M. Saito, Takumi Fujimura, Tatsuo Kuroda, Shigeru Ueno, Shoji Watanabe, Shunsuke Nosaka, Mikiko MiyasakaAbstract:Introduction: Lymphatic anomalies (LAs) refer to a group of diseases involving systemic dysplasia of Lymphatic vessels. These lesions are classified as Cystic Lymphatic Malformation (macroCystic, microCystic or mixed), generalized Lymphatic anomaly, and Gorham–Stout disease. LAs occur mainly in childhood, and present with various symptoms including chronic airway problems, recurrent infection, and organ disorders. Individuals with LAs often experience progressively worsening symptoms with a deteriorating quality of life. Although limited treatment options are available, their efficacy has not been validated in prospective clinical trials, and are usually based on case reports. Thus, there are no validated standards of care for these patients because of the lack of prospective clinical trials. Methods: This open-label, single-arm, multicenter, prospective study will assess the efficacy and safety of a mammalian target of the rapamycin inhibitor sirolimus in the treatment of intractable LAs. Participants will receive oral sirolimus once a day for 52 weeks. The dose is adjusted so that the nadir concentration remains within 5–15 ng/ml. The primary endpoint is the response rate of radiological volumetric change of the target lesion confirmed by central review at 52 weeks after treatment. The secondary endpoints are the response rates at 12 and 24 weeks, respiratory function, pleural effusion, ascites, blood coagulation parameters, bleeding, pain, quality of life, activities of daily living, adverse events, side effects, laboratory examinations, vital signs, and pharmacokinetic data. Results: This is among the first multicenter studies to evaluate sirolimus treatment for intractable LAs, and few studies to date have focused on the standard assessment of the efficacy for LAs treatment. Our protocol uses novel, uncomplicated methods for radiological assessment, with reference to the results of our previous retrospective survey and historical control data from the literature. Conclusions: We propose a multicenter study to investigate the efficacy and safety of sirolimus for intractable LAs (SILA study; trial registration UMIN000028905). Our results will provide pivotal data to support the approval of sirolimus for the treatment of intractable LAs. Keywords: Lymphatic abnormalities, Lymphatic Malformation, Generalized Lymphatic anomaly, Gorham–Stout disease, Mammalian target of rapamyci
Toshiyuki Fukao - One of the best experts on this subject based on the ideXlab platform.
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The impact of sirolimus therapy on lesion size, clinical symptoms, and quality of life of patients with Lymphatic anomalies.
Orphanet journal of rare diseases, 2019Co-Authors: Michio Ozeki, Akifumi Nozawa, Shiho Yasue, Saori Endo, Ryuta Asada, Hiroya Hashimoto, Toshiyuki FukaoAbstract:Lymphatic anomalies (LAs) include several disorders in which abnormal Lymphatic tissue invades the neck, chest, and various organs. Progressive cases may result in lethal outcomes and have proven difficult to treat. Sirolimus is showing promising results in the management of vascular anomalies. We examined the efficacy and safety of sirolimus treatment in patients with progressive LAs. All patients with LAs treated with sirolimus from May 2015 to September 2018 were included. They received oral sirolimus once a day and the dose was adjusted so that the trough concentration remained within 5–15 ng/mL. We prospectively reviewed the response to drugs (the response rate of radiological volumetric change of the target lesion), severity scores, reported quality of life (QOL), and adverse effects at 6 months after administration. Twenty patients (five with Cystic Lymphatic Malformation (LM), three with kaposiform lymphangiomatosis, three with generalized Lymphatic anomaly, six with Gorham-Stout disease, and three with central conducting Lymphatic anomaly) were treated with sirolimus at our institution. Fifty percent of patients (10/20) demonstrated a partial response by a radiological examination and a significant improvement in disease severity and QOL scores (P = 0.0020 and P = 0.0117, respectively). Ten patients who had no reduction in lesion size (stable disease group) showed no significant improvement in disease severity and QOL scores. Eighty percent of patients (16/20) had side effects, such as stomatitis, infection, and hyperlipidemia. Sirolimus impacts the reduction of the Lymphatic tissue volume of LMs and could lead to improvement in clinical symptoms and QOL. UMIN Clinical Trials Registry, UMIN000016580 . Registered 19 February 2015,
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The impact of sirolimus therapy on lesion size, clinical symptoms, and quality of life of patients with Lymphatic anomalies
Orphanet Journal of Rare Diseases, 2019Co-Authors: Michio Ozeki, Akifumi Nozawa, Shiho Yasue, Saori Endo, Ryuta Asada, Hiroya Hashimoto, Toshiyuki FukaoAbstract:Background Lymphatic anomalies (LAs) include several disorders in which abnormal Lymphatic tissue invades the neck, chest, and various organs. Progressive cases may result in lethal outcomes and have proven difficult to treat. Sirolimus is showing promising results in the management of vascular anomalies. We examined the efficacy and safety of sirolimus treatment in patients with progressive LAs. Methods All patients with LAs treated with sirolimus from May 2015 to September 2018 were included. They received oral sirolimus once a day and the dose was adjusted so that the trough concentration remained within 5–15 ng/mL. We prospectively reviewed the response to drugs (the response rate of radiological volumetric change of the target lesion), severity scores, reported quality of life (QOL), and adverse effects at 6 months after administration. Results Twenty patients (five with Cystic Lymphatic Malformation (LM), three with kaposiform lymphangiomatosis, three with generalized Lymphatic anomaly, six with Gorham-Stout disease, and three with central conducting Lymphatic anomaly) were treated with sirolimus at our institution. Fifty percent of patients (10/20) demonstrated a partial response by a radiological examination and a significant improvement in disease severity and QOL scores ( P = 0.0020 and P = 0.0117, respectively). Ten patients who had no reduction in lesion size (stable disease group) showed no significant improvement in disease severity and QOL scores. Eighty percent of patients (16/20) had side effects, such as stomatitis, infection, and hyperlipidemia. Conclusions Sirolimus impacts the reduction of the Lymphatic tissue volume of LMs and could lead to improvement in clinical symptoms and QOL. Trial registration UMIN Clinical Trials Registry, UMIN000016580 . Registered 19 February 2015,
Hiroya Hashimoto - One of the best experts on this subject based on the ideXlab platform.
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The impact of sirolimus therapy on lesion size, clinical symptoms, and quality of life of patients with Lymphatic anomalies.
Orphanet journal of rare diseases, 2019Co-Authors: Michio Ozeki, Akifumi Nozawa, Shiho Yasue, Saori Endo, Ryuta Asada, Hiroya Hashimoto, Toshiyuki FukaoAbstract:Lymphatic anomalies (LAs) include several disorders in which abnormal Lymphatic tissue invades the neck, chest, and various organs. Progressive cases may result in lethal outcomes and have proven difficult to treat. Sirolimus is showing promising results in the management of vascular anomalies. We examined the efficacy and safety of sirolimus treatment in patients with progressive LAs. All patients with LAs treated with sirolimus from May 2015 to September 2018 were included. They received oral sirolimus once a day and the dose was adjusted so that the trough concentration remained within 5–15 ng/mL. We prospectively reviewed the response to drugs (the response rate of radiological volumetric change of the target lesion), severity scores, reported quality of life (QOL), and adverse effects at 6 months after administration. Twenty patients (five with Cystic Lymphatic Malformation (LM), three with kaposiform lymphangiomatosis, three with generalized Lymphatic anomaly, six with Gorham-Stout disease, and three with central conducting Lymphatic anomaly) were treated with sirolimus at our institution. Fifty percent of patients (10/20) demonstrated a partial response by a radiological examination and a significant improvement in disease severity and QOL scores (P = 0.0020 and P = 0.0117, respectively). Ten patients who had no reduction in lesion size (stable disease group) showed no significant improvement in disease severity and QOL scores. Eighty percent of patients (16/20) had side effects, such as stomatitis, infection, and hyperlipidemia. Sirolimus impacts the reduction of the Lymphatic tissue volume of LMs and could lead to improvement in clinical symptoms and QOL. UMIN Clinical Trials Registry, UMIN000016580 . Registered 19 February 2015,
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The impact of sirolimus therapy on lesion size, clinical symptoms, and quality of life of patients with Lymphatic anomalies
Orphanet Journal of Rare Diseases, 2019Co-Authors: Michio Ozeki, Akifumi Nozawa, Shiho Yasue, Saori Endo, Ryuta Asada, Hiroya Hashimoto, Toshiyuki FukaoAbstract:Background Lymphatic anomalies (LAs) include several disorders in which abnormal Lymphatic tissue invades the neck, chest, and various organs. Progressive cases may result in lethal outcomes and have proven difficult to treat. Sirolimus is showing promising results in the management of vascular anomalies. We examined the efficacy and safety of sirolimus treatment in patients with progressive LAs. Methods All patients with LAs treated with sirolimus from May 2015 to September 2018 were included. They received oral sirolimus once a day and the dose was adjusted so that the trough concentration remained within 5–15 ng/mL. We prospectively reviewed the response to drugs (the response rate of radiological volumetric change of the target lesion), severity scores, reported quality of life (QOL), and adverse effects at 6 months after administration. Results Twenty patients (five with Cystic Lymphatic Malformation (LM), three with kaposiform lymphangiomatosis, three with generalized Lymphatic anomaly, six with Gorham-Stout disease, and three with central conducting Lymphatic anomaly) were treated with sirolimus at our institution. Fifty percent of patients (10/20) demonstrated a partial response by a radiological examination and a significant improvement in disease severity and QOL scores ( P = 0.0020 and P = 0.0117, respectively). Ten patients who had no reduction in lesion size (stable disease group) showed no significant improvement in disease severity and QOL scores. Eighty percent of patients (16/20) had side effects, such as stomatitis, infection, and hyperlipidemia. Conclusions Sirolimus impacts the reduction of the Lymphatic tissue volume of LMs and could lead to improvement in clinical symptoms and QOL. Trial registration UMIN Clinical Trials Registry, UMIN000016580 . Registered 19 February 2015,
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Efficacy and safety of sirolimus treatment for intractable Lymphatic anomalies: A study protocol for an open-label, single-arm, multicenter, prospective study (SILA)
Regenerative therapy, 2019Co-Authors: Michio Ozeki, Ryuta Asada, Hiroya Hashimoto, Takumi Fujimura, Tatsuo Kuroda, Shigeru Ueno, Shoji Watanabe, Shunsuke Nosaka, Akiko Saito, Mikiko MiyasakaAbstract:Abstract Introduction Lymphatic anomalies (LAs) refer to a group of diseases involving systemic dysplasia of Lymphatic vessels. These lesions are classified as Cystic Lymphatic Malformation (macroCystic, microCystic or mixed), generalized Lymphatic anomaly, and Gorham–Stout disease. LAs occur mainly in childhood, and present with various symptoms including chronic airway problems, recurrent infection, and organ disorders. Individuals with LAs often experience progressively worsening symptoms with a deteriorating quality of life. Although limited treatment options are available, their efficacy has not been validated in prospective clinical trials, and are usually based on case reports. Thus, there are no validated standards of care for these patients because of the lack of prospective clinical trials. Methods This open-label, single-arm, multicenter, prospective study will assess the efficacy and safety of a mammalian target of the rapamycin inhibitor sirolimus in the treatment of intractable LAs. Participants will receive oral sirolimus once a day for 52 weeks. The dose is adjusted so that the nadir concentration remains within 5–15 ng/ml. The primary endpoint is the response rate of radiological volumetric change of the target lesion confirmed by central review at 52 weeks after treatment. The secondary endpoints are the response rates at 12 and 24 weeks, respiratory function, pleural effusion, ascites, blood coagulation parameters, bleeding, pain, quality of life, activities of daily living, adverse events, side effects, laboratory examinations, vital signs, and pharmacokinetic data. Results This is among the first multicenter studies to evaluate sirolimus treatment for intractable LAs, and few studies to date have focused on the standard assessment of the efficacy for LAs treatment. Our protocol uses novel, uncomplicated methods for radiological assessment, with reference to the results of our previous retrospective survey and historical control data from the literature. Conclusions We propose a multicenter study to investigate the efficacy and safety of sirolimus for intractable LAs (SILA study; trial registration UMIN000028905). Our results will provide pivotal data to support the approval of sirolimus for the treatment of intractable LAs.
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Efficacy and safety of sirolimus treatment for intractable Lymphatic anomalies: A study protocol for an open-label, single-arm, multicenter, prospective study (SILA)
Elsevier, 2019Co-Authors: Michio Ozeki, Ryuta Asada, Hiroya Hashimoto, Akiko M. Saito, Takumi Fujimura, Tatsuo Kuroda, Shigeru Ueno, Shoji Watanabe, Shunsuke Nosaka, Mikiko MiyasakaAbstract:Introduction: Lymphatic anomalies (LAs) refer to a group of diseases involving systemic dysplasia of Lymphatic vessels. These lesions are classified as Cystic Lymphatic Malformation (macroCystic, microCystic or mixed), generalized Lymphatic anomaly, and Gorham–Stout disease. LAs occur mainly in childhood, and present with various symptoms including chronic airway problems, recurrent infection, and organ disorders. Individuals with LAs often experience progressively worsening symptoms with a deteriorating quality of life. Although limited treatment options are available, their efficacy has not been validated in prospective clinical trials, and are usually based on case reports. Thus, there are no validated standards of care for these patients because of the lack of prospective clinical trials. Methods: This open-label, single-arm, multicenter, prospective study will assess the efficacy and safety of a mammalian target of the rapamycin inhibitor sirolimus in the treatment of intractable LAs. Participants will receive oral sirolimus once a day for 52 weeks. The dose is adjusted so that the nadir concentration remains within 5–15 ng/ml. The primary endpoint is the response rate of radiological volumetric change of the target lesion confirmed by central review at 52 weeks after treatment. The secondary endpoints are the response rates at 12 and 24 weeks, respiratory function, pleural effusion, ascites, blood coagulation parameters, bleeding, pain, quality of life, activities of daily living, adverse events, side effects, laboratory examinations, vital signs, and pharmacokinetic data. Results: This is among the first multicenter studies to evaluate sirolimus treatment for intractable LAs, and few studies to date have focused on the standard assessment of the efficacy for LAs treatment. Our protocol uses novel, uncomplicated methods for radiological assessment, with reference to the results of our previous retrospective survey and historical control data from the literature. Conclusions: We propose a multicenter study to investigate the efficacy and safety of sirolimus for intractable LAs (SILA study; trial registration UMIN000028905). Our results will provide pivotal data to support the approval of sirolimus for the treatment of intractable LAs. Keywords: Lymphatic abnormalities, Lymphatic Malformation, Generalized Lymphatic anomaly, Gorham–Stout disease, Mammalian target of rapamyci
Ryuta Asada - One of the best experts on this subject based on the ideXlab platform.
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The impact of sirolimus therapy on lesion size, clinical symptoms, and quality of life of patients with Lymphatic anomalies.
Orphanet journal of rare diseases, 2019Co-Authors: Michio Ozeki, Akifumi Nozawa, Shiho Yasue, Saori Endo, Ryuta Asada, Hiroya Hashimoto, Toshiyuki FukaoAbstract:Lymphatic anomalies (LAs) include several disorders in which abnormal Lymphatic tissue invades the neck, chest, and various organs. Progressive cases may result in lethal outcomes and have proven difficult to treat. Sirolimus is showing promising results in the management of vascular anomalies. We examined the efficacy and safety of sirolimus treatment in patients with progressive LAs. All patients with LAs treated with sirolimus from May 2015 to September 2018 were included. They received oral sirolimus once a day and the dose was adjusted so that the trough concentration remained within 5–15 ng/mL. We prospectively reviewed the response to drugs (the response rate of radiological volumetric change of the target lesion), severity scores, reported quality of life (QOL), and adverse effects at 6 months after administration. Twenty patients (five with Cystic Lymphatic Malformation (LM), three with kaposiform lymphangiomatosis, three with generalized Lymphatic anomaly, six with Gorham-Stout disease, and three with central conducting Lymphatic anomaly) were treated with sirolimus at our institution. Fifty percent of patients (10/20) demonstrated a partial response by a radiological examination and a significant improvement in disease severity and QOL scores (P = 0.0020 and P = 0.0117, respectively). Ten patients who had no reduction in lesion size (stable disease group) showed no significant improvement in disease severity and QOL scores. Eighty percent of patients (16/20) had side effects, such as stomatitis, infection, and hyperlipidemia. Sirolimus impacts the reduction of the Lymphatic tissue volume of LMs and could lead to improvement in clinical symptoms and QOL. UMIN Clinical Trials Registry, UMIN000016580 . Registered 19 February 2015,
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The impact of sirolimus therapy on lesion size, clinical symptoms, and quality of life of patients with Lymphatic anomalies
Orphanet Journal of Rare Diseases, 2019Co-Authors: Michio Ozeki, Akifumi Nozawa, Shiho Yasue, Saori Endo, Ryuta Asada, Hiroya Hashimoto, Toshiyuki FukaoAbstract:Background Lymphatic anomalies (LAs) include several disorders in which abnormal Lymphatic tissue invades the neck, chest, and various organs. Progressive cases may result in lethal outcomes and have proven difficult to treat. Sirolimus is showing promising results in the management of vascular anomalies. We examined the efficacy and safety of sirolimus treatment in patients with progressive LAs. Methods All patients with LAs treated with sirolimus from May 2015 to September 2018 were included. They received oral sirolimus once a day and the dose was adjusted so that the trough concentration remained within 5–15 ng/mL. We prospectively reviewed the response to drugs (the response rate of radiological volumetric change of the target lesion), severity scores, reported quality of life (QOL), and adverse effects at 6 months after administration. Results Twenty patients (five with Cystic Lymphatic Malformation (LM), three with kaposiform lymphangiomatosis, three with generalized Lymphatic anomaly, six with Gorham-Stout disease, and three with central conducting Lymphatic anomaly) were treated with sirolimus at our institution. Fifty percent of patients (10/20) demonstrated a partial response by a radiological examination and a significant improvement in disease severity and QOL scores ( P = 0.0020 and P = 0.0117, respectively). Ten patients who had no reduction in lesion size (stable disease group) showed no significant improvement in disease severity and QOL scores. Eighty percent of patients (16/20) had side effects, such as stomatitis, infection, and hyperlipidemia. Conclusions Sirolimus impacts the reduction of the Lymphatic tissue volume of LMs and could lead to improvement in clinical symptoms and QOL. Trial registration UMIN Clinical Trials Registry, UMIN000016580 . Registered 19 February 2015,
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Efficacy and safety of sirolimus treatment for intractable Lymphatic anomalies: A study protocol for an open-label, single-arm, multicenter, prospective study (SILA)
Regenerative therapy, 2019Co-Authors: Michio Ozeki, Ryuta Asada, Hiroya Hashimoto, Takumi Fujimura, Tatsuo Kuroda, Shigeru Ueno, Shoji Watanabe, Shunsuke Nosaka, Akiko Saito, Mikiko MiyasakaAbstract:Abstract Introduction Lymphatic anomalies (LAs) refer to a group of diseases involving systemic dysplasia of Lymphatic vessels. These lesions are classified as Cystic Lymphatic Malformation (macroCystic, microCystic or mixed), generalized Lymphatic anomaly, and Gorham–Stout disease. LAs occur mainly in childhood, and present with various symptoms including chronic airway problems, recurrent infection, and organ disorders. Individuals with LAs often experience progressively worsening symptoms with a deteriorating quality of life. Although limited treatment options are available, their efficacy has not been validated in prospective clinical trials, and are usually based on case reports. Thus, there are no validated standards of care for these patients because of the lack of prospective clinical trials. Methods This open-label, single-arm, multicenter, prospective study will assess the efficacy and safety of a mammalian target of the rapamycin inhibitor sirolimus in the treatment of intractable LAs. Participants will receive oral sirolimus once a day for 52 weeks. The dose is adjusted so that the nadir concentration remains within 5–15 ng/ml. The primary endpoint is the response rate of radiological volumetric change of the target lesion confirmed by central review at 52 weeks after treatment. The secondary endpoints are the response rates at 12 and 24 weeks, respiratory function, pleural effusion, ascites, blood coagulation parameters, bleeding, pain, quality of life, activities of daily living, adverse events, side effects, laboratory examinations, vital signs, and pharmacokinetic data. Results This is among the first multicenter studies to evaluate sirolimus treatment for intractable LAs, and few studies to date have focused on the standard assessment of the efficacy for LAs treatment. Our protocol uses novel, uncomplicated methods for radiological assessment, with reference to the results of our previous retrospective survey and historical control data from the literature. Conclusions We propose a multicenter study to investigate the efficacy and safety of sirolimus for intractable LAs (SILA study; trial registration UMIN000028905). Our results will provide pivotal data to support the approval of sirolimus for the treatment of intractable LAs.
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Efficacy and safety of sirolimus treatment for intractable Lymphatic anomalies: A study protocol for an open-label, single-arm, multicenter, prospective study (SILA)
Elsevier, 2019Co-Authors: Michio Ozeki, Ryuta Asada, Hiroya Hashimoto, Akiko M. Saito, Takumi Fujimura, Tatsuo Kuroda, Shigeru Ueno, Shoji Watanabe, Shunsuke Nosaka, Mikiko MiyasakaAbstract:Introduction: Lymphatic anomalies (LAs) refer to a group of diseases involving systemic dysplasia of Lymphatic vessels. These lesions are classified as Cystic Lymphatic Malformation (macroCystic, microCystic or mixed), generalized Lymphatic anomaly, and Gorham–Stout disease. LAs occur mainly in childhood, and present with various symptoms including chronic airway problems, recurrent infection, and organ disorders. Individuals with LAs often experience progressively worsening symptoms with a deteriorating quality of life. Although limited treatment options are available, their efficacy has not been validated in prospective clinical trials, and are usually based on case reports. Thus, there are no validated standards of care for these patients because of the lack of prospective clinical trials. Methods: This open-label, single-arm, multicenter, prospective study will assess the efficacy and safety of a mammalian target of the rapamycin inhibitor sirolimus in the treatment of intractable LAs. Participants will receive oral sirolimus once a day for 52 weeks. The dose is adjusted so that the nadir concentration remains within 5–15 ng/ml. The primary endpoint is the response rate of radiological volumetric change of the target lesion confirmed by central review at 52 weeks after treatment. The secondary endpoints are the response rates at 12 and 24 weeks, respiratory function, pleural effusion, ascites, blood coagulation parameters, bleeding, pain, quality of life, activities of daily living, adverse events, side effects, laboratory examinations, vital signs, and pharmacokinetic data. Results: This is among the first multicenter studies to evaluate sirolimus treatment for intractable LAs, and few studies to date have focused on the standard assessment of the efficacy for LAs treatment. Our protocol uses novel, uncomplicated methods for radiological assessment, with reference to the results of our previous retrospective survey and historical control data from the literature. Conclusions: We propose a multicenter study to investigate the efficacy and safety of sirolimus for intractable LAs (SILA study; trial registration UMIN000028905). Our results will provide pivotal data to support the approval of sirolimus for the treatment of intractable LAs. Keywords: Lymphatic abnormalities, Lymphatic Malformation, Generalized Lymphatic anomaly, Gorham–Stout disease, Mammalian target of rapamyci
Saori Endo - One of the best experts on this subject based on the ideXlab platform.
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The impact of sirolimus therapy on lesion size, clinical symptoms, and quality of life of patients with Lymphatic anomalies.
Orphanet journal of rare diseases, 2019Co-Authors: Michio Ozeki, Akifumi Nozawa, Shiho Yasue, Saori Endo, Ryuta Asada, Hiroya Hashimoto, Toshiyuki FukaoAbstract:Lymphatic anomalies (LAs) include several disorders in which abnormal Lymphatic tissue invades the neck, chest, and various organs. Progressive cases may result in lethal outcomes and have proven difficult to treat. Sirolimus is showing promising results in the management of vascular anomalies. We examined the efficacy and safety of sirolimus treatment in patients with progressive LAs. All patients with LAs treated with sirolimus from May 2015 to September 2018 were included. They received oral sirolimus once a day and the dose was adjusted so that the trough concentration remained within 5–15 ng/mL. We prospectively reviewed the response to drugs (the response rate of radiological volumetric change of the target lesion), severity scores, reported quality of life (QOL), and adverse effects at 6 months after administration. Twenty patients (five with Cystic Lymphatic Malformation (LM), three with kaposiform lymphangiomatosis, three with generalized Lymphatic anomaly, six with Gorham-Stout disease, and three with central conducting Lymphatic anomaly) were treated with sirolimus at our institution. Fifty percent of patients (10/20) demonstrated a partial response by a radiological examination and a significant improvement in disease severity and QOL scores (P = 0.0020 and P = 0.0117, respectively). Ten patients who had no reduction in lesion size (stable disease group) showed no significant improvement in disease severity and QOL scores. Eighty percent of patients (16/20) had side effects, such as stomatitis, infection, and hyperlipidemia. Sirolimus impacts the reduction of the Lymphatic tissue volume of LMs and could lead to improvement in clinical symptoms and QOL. UMIN Clinical Trials Registry, UMIN000016580 . Registered 19 February 2015,
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The impact of sirolimus therapy on lesion size, clinical symptoms, and quality of life of patients with Lymphatic anomalies
Orphanet Journal of Rare Diseases, 2019Co-Authors: Michio Ozeki, Akifumi Nozawa, Shiho Yasue, Saori Endo, Ryuta Asada, Hiroya Hashimoto, Toshiyuki FukaoAbstract:Background Lymphatic anomalies (LAs) include several disorders in which abnormal Lymphatic tissue invades the neck, chest, and various organs. Progressive cases may result in lethal outcomes and have proven difficult to treat. Sirolimus is showing promising results in the management of vascular anomalies. We examined the efficacy and safety of sirolimus treatment in patients with progressive LAs. Methods All patients with LAs treated with sirolimus from May 2015 to September 2018 were included. They received oral sirolimus once a day and the dose was adjusted so that the trough concentration remained within 5–15 ng/mL. We prospectively reviewed the response to drugs (the response rate of radiological volumetric change of the target lesion), severity scores, reported quality of life (QOL), and adverse effects at 6 months after administration. Results Twenty patients (five with Cystic Lymphatic Malformation (LM), three with kaposiform lymphangiomatosis, three with generalized Lymphatic anomaly, six with Gorham-Stout disease, and three with central conducting Lymphatic anomaly) were treated with sirolimus at our institution. Fifty percent of patients (10/20) demonstrated a partial response by a radiological examination and a significant improvement in disease severity and QOL scores ( P = 0.0020 and P = 0.0117, respectively). Ten patients who had no reduction in lesion size (stable disease group) showed no significant improvement in disease severity and QOL scores. Eighty percent of patients (16/20) had side effects, such as stomatitis, infection, and hyperlipidemia. Conclusions Sirolimus impacts the reduction of the Lymphatic tissue volume of LMs and could lead to improvement in clinical symptoms and QOL. Trial registration UMIN Clinical Trials Registry, UMIN000016580 . Registered 19 February 2015,
