Congenital Muscle Disease Study of Patient and Family Reported Medical Information

Официальное название

Congenital Muscle Disease Patient and Proxy Reported Outcome Study

Обзор

The Congenital Muscle Disease Patient and Proxy Reported Outcome Study (CMDPROS) is a longitudinal 10 year study to identify and trend care parameters, adverse events in the congenital muscle diseases using the Congenital Muscle Disease International Registry (CMDIR) to acquire necessary data for adverse event calculations (intake survey and medical records curation). To support this study and become a participant, we ask that you register in the CMDIR. You can do this by visiting www.cmdir.org. There is no travel required. The registry includes affected individuals with congenital muscular dystrophy, congenital myopathy, and congenital myasthenic syndrome and registers through the late onset spectrum for these disease groups. The CMDIR was created to identify the global congenital muscle disease population for the purpose of raising awareness, standards of care, clinical trials and in the future a treatment or cure. Simply put, we will not be successful in finding a treatment or cure unless we know who the affected individuals are, what the diagnosis is and how the disease is affecting the individual. Registering in the CMDIR means that you will enter demographic information and complete an intake survey. We would then ask that you provide records regarding the diagnosis and treatment of CMD, including genetic testing, muscle biopsy, pulmonary function testing, sleep studies, clinic visit notes, and hospital discharge summaries. Study hypothesis: 1. To use patient and proxy reported survey answers and medical reports to build a longitudinal care and outcomes database across the congenital muscle diseases. 2. To generate congenital muscle disease subtype specific adverse event rates and correlate with key care parameters.

Подробное описание

The Congenital Muscle Disease Patient and Proxy Reported Outcome Study (CMDPROS) is a longitudinal 10 year observational study to identify care and trend key care parameters and adverse events in the congenital muscle diseases using the Congenital Muscle Disease International Registry (CMDIR). The CMDIR registers individuals with and without genetic confirmation who have been given a clinical diagnosis of congenital muscular dystrophy, congenital myopathy, and congenital myasthenic syndrome, or myofibrillar myopathy, through the limb girdle/late onset spectrum.

Identifying care parameters and adverse events in the rare genetic neuromuscular diseases can be difficult. Care is fragmented, genetic confirmation may not be prioritized by the medical community or covered by medical insurance and patients are scattered globally with potential challenges aggregating data across centers. Natural history studies are currently being launched. However, potential biases to participation include recruitment of the less severely affected patients given difficulty traveling secondary to a medically fragile condition. There is currently no treatment for these conditions; though optimizing and standardizing care and care delivery can promote significant gains in quality of life and survival. Identifying disease specific care parameters and correlating those parameters with adverse event rates will not only contribute to the development of evidence based guidelines but inform clinically meaningful outcomes for future clinical trials.

Study hypothesis:

1. To use patient and proxy reported survey answers and medical reports to build a longitudinal care and outcomes database across the congenital muscle diseases. 2. To generate congenital muscle disease subtype specific adverse event rates and correlate with key care parameters.

Primary outcome is survival measured from date of birth to date of death. Primary outcome will be analyzed by congenital muscle disease subtype and maximal ambulatory status achieved.

Secondary outcomes include disease specific adverse event rates including rates of hospitalization, rates of antibiotic use, rates of pulmonary infections, pneumothorax, atelectasis, aspiration and adverse complaints including bloating, constipation, chest pain, dyspnea assessed by a validated breathing assessment, vomiting and nausea and difficulty eating. Patient and proxy hospitalization, pneumothorax and atelectasis reports will be confirmed by obtaining hospital discharge summaries. Additional secondary outcomes include ejection fraction (relevance subtype specific), forced vital capacity in liters, weight, Rapid Eye Movement (REM) sleep apnea hypopnea index and mean oxygen saturation during REM and total sleep study, age, gender, type of treatment center location (national referral center, tertiary care hospital, community hospital), gastrostomy tube, total number of fractures and Tscore/Zscore of hip and spine on DEXA scans.

Preliminary studies may focus on specific congenital muscle disease subtypes and use retrospective data collection through registry, survey monkey and telephone interviews to assess adverse event rates over last month and last year to limit recall bias. Prospective enrollment of same study participants over 12 months will assess monthly rates of adverse events and complaints. A preliminary study, CMD PROADE (Patient and Proxy Reported ADverse Event Rates) is planned in 2 congenital muscular dystrophy subtypes: Collagen 6 Myopathy and LAMA 2 Related CMD.

De-identified data from CMDIR will be made available for IRB approved natural history studies in the congenital muscle diseases.

Первичные конечные точки

• Congenital Muscle Disease Patient and Proxy Reported Outcomes [Срок оценки: 10 years]

Критерии участия

Критерии включения

Alpha 7/Alpha 9 Integrin Related Myopathy Collagen VI Related Myopathy (Ullrich through Bethlem CMD) Alpha-Dystroglycan Related Muscular Dystrophy (Dystroglycanopathy, WWS, MEB, Fukuyama, FKRP, LGMD2I, LGMD2K, LGMD2M, LGMD2N, LGMD2O) Choline Kinase B Receptor Emery-Dreifuss Muscular Dystrophy (EDMD, LGMD1B, LMNA, Emerin, FHL1, SYNE1, SYNE2, TMEM43) LAMA2 Related Muscular Dystrophy (Laminin Alpha 2 related dystrophy/MDC1A/Merosin deficient) LMNA Related Muscular Dystrophy (Laminopathy/LaminA/C, L-CMD, Emery Dreifuss muscular dystrophy) RYR1 Related Myopathy (with dystrophic presentation, including Malignant Hyperthermia, Exertional Myalgia with or without Rhabdomyolysis) SEPN1 Related Myopathy (Rigid Spine Muscular Dystrophy/RSMD1, Congenital Fiber Type Disproportion, Mallory Weiss Body Desmin, Multi-minicore Myopathy) SYNE1 (Nesprin Related Muscular Dystrophy) Telethonin Related Muscular Dystrophy (TCAP/Titin-Cap) Congenital Muscular Dystrophy Not Otherwise Specified (including Merosin Positive) Titin Related LGMD/CMD, LGMD2J Actin Aggregation Myopathy Cap Disease Central Core Disease (including Malignant Hyperthermia, Exertional Myalgia with or without Rhabdomyolysis) Centronuclear Myopathy (including Malignant Hyperthermia, Exertional Myalgia with or without Rhabdomyolysis) Congenital Fiber Type Disproportion (including Malignant Hyperthermia, Exertional Myalgia with or without Rhabdomyolysis) Core Rod Myopathy Hyaline Body Myopathy Multiminicore Myopathy Myotubular Myopathy Nemaline Myopathy Reducing Body Myopathy RYR1 Related Myopathy (including Malignant Hyperthermia, Exertional Myalgia with or without Rhabdomyolysis) Spheroid Body Myopathy Titin Related Myopathy, Titin Related Dialated Cardiomyopathy, LGMD2J Tubular Aggregate Myopathy Zebra Body Disease Myopathy Congenital Myopathy Not Otherwise Specified Congenital Myasthenic Syndrome Escobar Syndrome Myofibrillar Myopathy

Критерии исключения

Charcot Marie Tooth Duchenne/Becker Muscular Dystrophy Facioscapulohumeral Dystrophy/FSHD Kennedy's Disease LGMD-1A (TTID) LGMD-1C (CAV3, Caveloin 3, Caveolinopathy, LQT9, VIP21) LGMD-1D (7q) LGMD-1E (6q23) LGMD-1F (7q32.1-q32.2) LGMD-1G (4q21) LGMD-2A (CAPN3/Calpainopathy) LGMD-2B (DYSF/Dysferlinopathy/Miyoshi Myopathy) LGMD-2C (SGCG) LGMD-2D (SGCA) LGMD-2E (SGCB) LGMD-2F (SGCD) LGMD-2L (AN05/Anoctamin 5) Lipodystrophy Myotonic Dystrophy Oculopharyngeal Muscular Dystrophy Spinal Muscular Atrophy

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

США · 1 центр

• Congenital Muscle Disease International Registry (www.cmdir.org) — Lakewood

Публикации

• Bonnemann CG, Rutkowski A, Mercuri E, Muntoni F; CMD Outcomes Consortium. 173rd ENMC International Workshop: congenital muscular dystrophy outcome measures 5-7 March 2010, Naarden, The Netherlands. Neuromuscul Disord. 2011 Jul;21(7):513-22. doi: 10.1016/j.nmd.2011.04.004. Epub 2011 Jun 8. No abstract available. PMID 21641800
• Wang CH, Bonnemann CG, Rutkowski A, Sejersen T, Bellini J, Battista V, Florence JM, Schara U, Schuler PM, Wahbi K, Aloysius A, Bash RO, Beroud C, Bertini E, Bushby K, Cohn RD, Connolly AM, Deconinck N, Desguerre I, Eagle M, Estournet-Mathiaud B, Ferreiro A, Fujak A, Goemans N, Iannaccone ST, Jouinot P, Main M, Melacini P, Mueller-Felber W, Muntoni F, Nelson LL, Rahbek J, Quijano-Roy S, Sewry C, St PMID 21078917
• Sparks SE, Quijano-Roy S, Harper A, Rutkowski A, Gordon E, Hoffman EP, Pegoraro E. Congenital Muscular Dystrophy Overview - RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY. 2001 Jan 22 [updated 2012 Aug 23]. In: Adam MP, Bick S, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2026. Available from http://www.ncbi.n PMID 20301468
• Geranmayeh F, Clement E, Feng LH, Sewry C, Pagan J, Mein R, Abbs S, Brueton L, Childs AM, Jungbluth H, De Goede CG, Lynch B, Lin JP, Chow G, Sousa Cd, O'Mahony O, Majumdar A, Straub V, Bushby K, Muntoni F. Genotype-phenotype correlation in a large population of muscular dystrophy patients with LAMA2 mutations. Neuromuscul Disord. 2010 Apr;20(4):241-50. doi: 10.1016/j.nmd.2010.02.001. Epub 2010 Mar PMID 20207543
• Sewry CA, Jimenez-Mallebrera C, Muntoni F. Congenital myopathies. Curr Opin Neurol. 2008 Oct;21(5):569-75. doi: 10.1097/WCO.0b013e32830f93c7. PMID 18769251
• Klein A, Clement E, Mercuri E, Muntoni F. Differential diagnosis of congenital muscular dystrophies. Eur J Paediatr Neurol. 2008 Sep;12(5):371-7. doi: 10.1016/j.ejpn.2007.10.002. Epub 2007 Dec 3. PMID 18588847
• Godfrey C, Clement E, Mein R, Brockington M, Smith J, Talim B, Straub V, Robb S, Quinlivan R, Feng L, Jimenez-Mallebrera C, Mercuri E, Manzur AY, Kinali M, Torelli S, Brown SC, Sewry CA, Bushby K, Topaloglu H, North K, Abbs S, Muntoni F. Refining genotype phenotype correlations in muscular dystrophies with defective glycosylation of dystroglycan. Brain. 2007 Oct;130(Pt 10):2725-35. doi: 10.1093/br PMID 17878207
• Ramelli GP, Aloysius A, King C, Davis T, Muntoni F. Gastrostomy placement in paediatric patients with neuromuscular disorders: indications and outcome. Dev Med Child Neurol. 2007 May;49(5):367-71. doi: 10.1111/j.1469-8749.2007.00367.x. PMID 17489811

Идентификаторы

NCT: NCT01403402 · CMDPROS1

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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