The SPARKLE registry: a multicenter, multinational, noninterventional, prospective cohort registry study in patients with alpha-mannosidosis

Abstract Background Alpha-mannosidosis is a lysosomal storage disorder caused by reduced enzymatic activity of alpha-mannosidase. Intracellular accumulation of mannose-rich oligosaccharides leads to a continuum of various heterogeneous clinical symptoms. Velmanase alfa (Lamzede®) is a human recombinant alpha-mannosidase approved in Europe in 2018 as the first enzyme replacement therapy for the treatment of non-neurologic manifestations in patients with mild-to-moderate alpha-mannosidosis. SPARKLE is an alpha-mannosidosis registry study intended to obtain long-term safety and effectiveness data on the use of velmanase alfa during routine clinical care in patients with alpha-mannosidosis and is a post-approval commitment to European marketing authorization. In addition, SPARKLE will expand the current understanding of alpha-mannosidosis by collecting data on the clinical manifestations, progression, and natural history of the disease in treated and untreated patients, respectively. Results SPARKLE is a post-authorization safety and efficacy registry designed as a multicenter, multinational, noninterventional, prospective cohort study of patients with alpha-mannosidosis, starting in 2020. Patients will be followed for up to 15 years. Safety and effectiveness outcomes under routine clinical care will be evaluated. The primary safety outcomes are the rate of adverse events (anti-velmanase alfa-immunoglobulin G antibody development, infusion-related reactions, and hypersensitivity). Secondary safety outcomes include the evaluation of medical events, change in vital signs, laboratory tests, physical examination, and electrocardiogram results. The primary effectiveness outcome is a global treatment response rate, evaluated as the individual aggregate of single endpoints from pharmacodynamic, functional, and quality of life effectiveness outcomes; secondary effectiveness outcomes are to characterize the population of patients with alpha-mannosidosis with regard to clinical manifestation, progression, and natural history of the disease. Any patient in the European Union with a diagnosis of alpha-mannosidosis who is willing to participate will likely be eligible for inclusion in the registry. Publications to disseminate scientific insights from the registry are planned. Conclusion This study will provide real-world data on the long-term safety and effectiveness of velmanase alfa in patients with alpha-mannosidosis during routine clinical care and increase the understanding of the natural course, clinical manifestations, and progression of this ultra-rare disease.

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The SPARKLE registry: protocol for an international prospective cohort study in patients with alpha-mannosidosis

10.21203/rs.2.19376/v2 ◽

2020 ◽

Author(s):

Julia Hennermann ◽

Nathalie Guffon ◽

Federica Cattaneo ◽

Ferdinando Ceravolo ◽

Line Borgwardt ◽

...

Keyword(s):

Cohort Study ◽

Natural History ◽

Prospective Cohort Study ◽

Prospective Cohort ◽

Clinical Care ◽

Clinical Manifestations ◽

Routine Clinical Care ◽

Safety Outcomes ◽

History Of

Abstract Background: Alpha-mannosidosis is a lysosomal storage disorder caused by reduced enzymatic activity of alpha-mannosidase. SPARKLE is an alpha-mannosidosis registry intended to obtain long-term safety and effectiveness data on the use of velmanase alfa during routine clinical care in patients with alpha-mannosidosis. It is a post-approval commitment to European marketing authorization for Velmanase alfa (Lamzede®), the first enzyme replacement therapy for the treatment of non-neurologic manifestations in patients with mild to moderate alpha-mannosidosis. In addition, SPARKLE will expand the current understanding of alpha-mannosidosis by collecting data on the clinical manifestations, progression, and natural history of the disease in treated and untreated patients, respectively.Results: The SPARKLE registry is designed as a multicenter, multinational, noninterventional, prospective cohort study of patients with alpha-mannosidosis, starting patient enrollment in 2020. Patients will be followed for up to 15 years. Safety and effectiveness as post-authorization outcomes under routine clinical care in patients with treatment will be evaluated. The primary safety outcomes are the rate of adverse events (anti-velmanase alfa-immunoglobulin G antibody development, infusion-related reactions, and hypersensitivity). Secondary safety outcomes include the evaluation of medical events, change in vital signs, laboratory tests, physical examination, and electrocardiogram results. The primary effectiveness outcome is a global treatment response rate, evaluated as the individual aggregate of single endpoints from pharmacodynamic, functional, and quality of life effectiveness outcomes; secondary effectiveness outcomes are to characterize the population of patients with alpha-mannosidosis with regard to clinical manifestation, progression, and natural history of the disease. Any patient in the European Union with a diagnosis of alpha-mannosidosis who is willing to participate will likely be eligible for inclusion in the registry. Publications to disseminate scientific insights from the registry are planned. Conclusion: This study will provide real-world data on the long-term safety and effectiveness of velmanase alfa in patients with alpha-mannosidosis during routine clinical care and increase the understanding of the natural course, clinical manifestations, and progression of this ultra-rare disease.

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The SPARKLE registry: protocol for an international prospective cohort study in patients with alpha-mannosidosis

Orphanet Journal of Rare Diseases ◽

10.1186/s13023-020-01549-8 ◽

2020 ◽

Vol 15 (1) ◽

Author(s):

Julia B. Hennermann ◽

Nathalie Guffon ◽

Federica Cattaneo ◽

Ferdinando Ceravolo ◽

Line Borgwardt ◽

...

Keyword(s):

Cohort Study ◽

Natural History ◽

Prospective Cohort Study ◽

Prospective Cohort ◽

Clinical Care ◽

Clinical Manifestations ◽

Routine Clinical Care ◽

Safety Outcomes ◽

History Of

Abstract Background Alpha-mannosidosis is a lysosomal storage disorder caused by reduced enzymatic activity of alpha-mannosidase. SPARKLE is an alpha-mannosidosis registry intended to obtain long-term safety and effectiveness data on the use of velmanase alfa during routine clinical care in patients with alpha-mannosidosis. It is a post-approval commitment to European marketing authorization for Velmanase alfa (Lamzede®), the first enzyme replacement therapy for the treatment of non-neurologic manifestations in patients with mild to moderate alpha-mannosidosis. In addition, SPARKLE will expand the current understanding of alpha-mannosidosis by collecting data on the clinical manifestations, progression, and natural history of the disease in treated and untreated patients, respectively. Results The SPARKLE registry is designed as a multicenter, multinational, noninterventional, prospective cohort study of patients with alpha-mannosidosis, starting patient enrollment in 2020. Patients will be followed for up to 15 years. Safety and effectiveness as post-authorization outcomes under routine clinical care in patients with treatment will be evaluated. The primary safety outcomes are the rate of adverse events (anti-velmanase alfa-immunoglobulin G antibody development, infusion-related reactions, and hypersensitivity). Secondary safety outcomes include the evaluation of medical events, change in vital signs, laboratory tests, physical examination, and electrocardiogram results. The primary effectiveness outcome is a global treatment response rate, evaluated as the individual aggregate of single endpoints from pharmacodynamic, functional, and quality-of-life effectiveness outcomes; secondary effectiveness outcomes are to characterize the population of patients with alpha-mannosidosis with regard to clinical manifestation, progression, and natural history of the disease. Any patient in the European Union with a diagnosis of alpha-mannosidosis who is willing to participate will likely be eligible for inclusion in the registry. Publications to disseminate scientific insights from the registry are planned. Conclusion This study will provide real-world data on the long-term safety and effectiveness of velmanase alfa in patients with alpha-mannosidosis during routine clinical care and increase the understanding of the natural course, clinical manifestations, and progression of this ultra-rare disease.

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The Natural history of Epicardial Adipose Tissue Volume and Attenuation: A long-term prospective cohort follow-up study

Scientific Reports ◽

10.1038/s41598-020-63135-z ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Nitesh Nerlekar ◽

Udit Thakur ◽

Andrew Lin ◽

Ji Quan Samuel Koh ◽

Elizabeth Potter ◽

...

Keyword(s):

Adipose Tissue ◽

Natural History ◽

Prospective Cohort ◽

Epicardial Adipose Tissue ◽

Tissue Volume ◽

Follow Up Study ◽

History Of ◽

Adipose Tissue Volume

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The natural history of pituitary apoplexy: long term follow-up study

Endocrine Abstracts ◽

10.1530/endoabs.65.p301 ◽

2019 ◽

Author(s):

Ayesha Shaikh ◽

Natasha Shrikrishnapalasuriyar ◽

Giselle Sharaf ◽

David Price ◽

Maneesh Udiawar ◽

...

Keyword(s):

Natural History ◽

Pituitary Apoplexy ◽

Follow Up Study ◽

Long Term Follow Up ◽

History Of

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Faculty Opinions recommendation of Natural history of imatinib-naive GISTs: a retrospective analysis of 929 cases with long-term follow-up and development of a survival nomogram based on mitotic index and size as continuous variables.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.13356067.14726207 ◽

2011 ◽

Author(s):

Richard Riedel

Keyword(s):

Natural History ◽

Retrospective Analysis ◽

Mitotic Index ◽

Continuous Variables ◽

Long Term Follow Up ◽

History Of

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The physiopathology of spontaneous hemorrhagic stroke: a systematic review

Reviews in the Neurosciences ◽

10.1515/revneuro-2020-0131 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Alcivan Batista de Morais Filho ◽

Thiago Luis de Holanda Rego ◽

Letícia de Lima Mendonça ◽

Sulyanne Saraiva de Almeida ◽

Mariana Lima da Nóbrega ◽

...

Keyword(s):

Risk Factors ◽

Systematic Review ◽

Ischemic Stroke ◽

Subarachnoid Hemorrhage ◽

Natural History ◽

Hemorrhagic Stroke ◽

Recent Literature ◽

Clinical Manifestations ◽

The Road ◽

History Of

Abstract Hemorrhagic stroke (HS) is a major cause of death and disability worldwide, despite being less common, it presents more aggressively and leads to more severe sequelae than ischemic stroke. There are two types of HS: Intracerebral Hemorrhage (ICH) and Subarachnoid Hemorrhage (SAH), differing not only in the site of bleeding, but also in the mechanisms responsible for acute and subacute symptoms. This is a systematic review of databases in search of works of the last five years relating to the comprehension of both kinds of HS. Sixty two articles composed the direct findings of the recent literature and were further characterized to construct the pathophysiology in the order of events. The road to the understanding of the spontaneous HS pathophysiology is far from complete. Our findings show specific and individual results relating to the natural history of the disease of ICH and SAH, presenting common and different risk factors, distinct and similar clinical manifestations at onset or later days to weeks, and possible complications for both.

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Long-term Natural History of Dry Eye Disease from the Patient's Perspective

Ophthalmology ◽

10.1016/j.ophtha.2015.10.011 ◽

2016 ◽

Vol 123 (2) ◽

pp. 425-433 ◽

Cited By ~ 23

Author(s):

Jeffrey P. Lienert ◽

Laura Tarko ◽

Miki Uchino ◽

William G. Christen ◽

Debra A. Schaumberg

Keyword(s):

Natural History ◽

Dry Eye ◽

Dry Eye Disease ◽

Eye Disease ◽

Patient’S Perspective ◽

History Of

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The Natural History of Long-Term Cardiac Pacing

The Annals of Thoracic Surgery ◽

10.1016/s0003-4975(10)63700-9 ◽

1977 ◽

Vol 23 (6) ◽

pp. 550-554 ◽

Cited By ~ 10

Author(s):

William S. Stoney ◽

Frederick E. Finger ◽

William C. Alford ◽

George R. Burrus ◽

Robert A. Frist ◽

...

Keyword(s):

Natural History ◽

Cardiac Pacing ◽

History Of

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Effects of long-term chloroquine administration on the natural history of aortic aneurysms in mice

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2015-0068 ◽

2015 ◽

Vol 93 (8) ◽

pp. 641-648 ◽

Cited By ~ 8

Author(s):

Azza Ramadan ◽

Mark D. Wheatcroft ◽

Adrian Quan ◽

Krishna K. Singh ◽

Fina Lovren ◽

...

Keyword(s):

Natural History ◽

Thrombus Formation ◽

Aortic Aneurysms ◽

Ang Ii ◽

Abdominal Aortic ◽

Suprarenal Aorta ◽

History Of ◽

Categorical Distribution

Autophagy regulates cellular homeostasis and integrates the cellular pro-survival machinery. We investigated the role of autophagy in the natural history of murine abdominal aortic aneurysms (AAA). ApoE−/− mice were implanted with saline- or angiotensin II (Ang-II)-filled miniosmotic pumps then treated with either the autophagy inhibitor chloroquine (CQ; 50 mg·(kg body mass)–1·day–1, by intraperitoneal injection) or saline. Ang-II-elicited aneurysmal expansion of the suprarenal aorta coupled with thrombus formation were apparent 8 weeks later. CQ had no impact on the incidence (50% for Ang-II compared with 46.2% for Ang-II + CQ; P = NS) and categorical distribution of aneurysms. The markedly reduced survival rate observed with Ang-II (57.1% for Ang-II compared with 100% for saline; P < 0.05) was unaffected by CQ (61.5% for Ang-II + CQ; P = NS compared with Ang-II). CQ did not affect the mean maximum suprarenal aortic diameter (1.91 ± 0.19 mm for Ang-II compared with 1.97 ± 0.21 mm for Ang-II + CQ; P = NS). Elastin fragmentation, collagen accumulation, and smooth muscle attrition, which were higher in Ang-II-treated mice, were unaffected by CQ treatment. Long-term CQ administration does not affect the natural history and prognosis of experimental AAA, suggesting that global loss of autophagy is unlikely to be a causal factor in the development of aortic aneurysms. Manipulation of autophagy as a mechanism to reduce AAA may need re-evaluation.

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