Natural history, outcome measures and trial readiness in LAMA2-related muscular dystrophy and SELENON-related myopathy in children and adults: protocol of the LAST STRONG study
| Autor: | Jos M. T. Draaisma, Jonne Doorduin, Nicol C. Voermans, Florence H J van Tienen, Hubert J.M. Smeets, Baziel G.M. van Engelen, Jan A.M. Smeitink, Nens van Alfen, Saskia Koene, Benno Küsters, Willem C M van Tilburg, Mirian C. H. Janssen, Floris E A Udink Ten Cate, Corrie E. Erasmus, Robin Nijveldt, Anne T. M. Dittrich, Karlijn Bouman, Frederik M. A. van den Heuvel, Jan T. Groothuis, Stan Buckens, Esmee S.B. Van Kleef, Erik-Jan Kamsteeg |
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| Přispěvatelé: | RS: MHeNs - R3 - Neuroscience, Toxicogenomics, RS: GROW - R4 - Reproductive and Perinatal Medicine, RS: FHML MaCSBio |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Pediatrics
Vascular damage Radboud Institute for Health Sciences [Radboudumc 16] Outcome measures Sensory disorders Donders Center for Medical Neuroscience [Radboudumc 12] Muscular Dystrophies Pulmonary function testing Study Protocol Outcome Assessment Health Care Laminin subunit α2 deficiency SEPN1 Prospective Studies Muscular dystrophy OXIDATIVE STRESS Child ULTRASOUND SELENOPROTEIN-N medicine.diagnostic_test All ages Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6] General Medicine Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3] Magnetic Resonance Imaging RELIABILITY Congenital muscular dystrophy medicine.symptom Natural history study SKELETAL-MUSCLE PATHOLOGY CLINICAL-TRIALS Rare cancers Radboud Institute for Health Sciences [Radboudumc 9] Adult medicine.medical_specialty Trial readiness QUESTIONNAIRE Natural history DUCHENNE DYSTROPHY Other Research Donders Center for Medical Neuroscience [Radboudumc 0] Neurological examination VALIDATION Healthcare improvement science Radboud Institute for Health Sciences [Radboudumc 18] All institutes and research themes of the Radboud University Medical Center medicine Humans LAMA2 Myopathy SELENON RC346-429 Laminin subunit a2 deficiency business.industry Other Research Radboud Institute for Health Sciences [Radboudumc 0] Metabolic Disorders Radboud Institute for Health Sciences [Radboudumc 6] Merosin-deficient congenital muscular dystrophy type 1A (MDC1A) medicine.disease Congenital myopathy REFERENCE VALUES Clinical trial Neurology (clinical) Laminin Neurology. Diseases of the nervous system business |
| Zdroj: | BMC Neurology, Vol 21, Iss 1, Pp 1-14 (2021) BMC Neurology, 21 BMC Neurology BMC Neurology, 21, 1 BMC Neurology, 21(1):313. BioMed Central Ltd |
| ISSN: | 1471-2377 |
| Popis: | BackgroundSELENON (SEPN1)-related myopathy (SELENON-RM) is a rare congenital myopathy characterized by slowly progressive proximal muscle weakness, early onset spine rigidity and respiratory insufficiency. A muscular dystrophy caused by mutations in theLAMA2gene (LAMA2-related muscular dystrophy, LAMA2-MD) has a similar clinical phenotype, with either a severe, early-onset due to complete Laminin subunit α2 deficiency (merosin-deficient congenital muscular dystrophy type 1A (MDC1A)), or a mild, childhood- or adult-onset due to partial Laminin subunit α2 deficiency. For both muscle diseases, no curative treatment options exist, yet promising preclinical studies are ongoing. Currently, there is a paucity on natural history data and appropriate clinical and functional outcome measures are needed to reach trial readiness.MethodsLAST STRONG is a natural history study in Dutch-speaking patients of all ages diagnosed with SELENON-RM or LAMA2-MD, starting August 2020. Patients have four visits at our hospital over a period of 1.5 year. At all visits, they undergo standardized neurological examination, hand-held dynamometry (age ≥ 5 years), functional measurements, questionnaires (patient report and/or parent proxy; age ≥ 2 years), muscle ultrasound including diaphragm, pulmonary function tests (spirometry, maximal inspiratory and expiratory pressure, sniff nasal inspiratory pressure; age ≥ 5 years), and accelerometry for 8 days (age ≥ 2 years); at visit one and three, they undergo cardiac evaluation (electrocardiogram, echocardiography; age ≥ 2 years), spine X-ray (age ≥ 2 years), dual-energy X-ray absorptiometry (DEXA-)scan (age ≥ 2 years) and full body magnetic resonance imaging (MRI) (age ≥ 10 years). All examinations are adapted to the patient’s age and functional abilities. Correlation between key parameters within and between subsequent visits will be assessed.DiscussionOur study will describe the natural history of patients diagnosed with SELENON-RM or LAMA2-MD, enabling us to select relevant clinical and functional outcome measures for reaching clinical trial-readiness. Moreover, our detailed description (deep phenotyping) of the clinical features will optimize clinical management and will establish a well-characterized baseline cohort for prospective follow-up.ConclusionOur natural history study is an essential step for reaching trial readiness in SELENON-RM and LAMA2-MD.Trial registrationThis study has been approved by medical ethical reviewing committee Region Arnhem-Nijmegen (NL64269.091.17, 2017–3911) and is registered atClinicalTrial.gov(NCT04478981). |
| Databáze: | OpenAIRE |
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