Long-Term Development of Muscular Dystrophy Outcome Assessments

Официальное название

Long-Term Development of Muscular Dystrophy Outcome Assessments (GRASP-01-005)

Обзор

This is a 24-month, observational study of up to 1000 participants with Limb Girdle Muscular Dystrophy (LGMD), Myotonic Dystrophy Type 2 (DM2), and late onset Pompe disease (LOPD).

Подробное описание

Limb Girdle Muscular Dystrophy (LGMD) comprise a group of disorders made up of over 30 mutations which share a common phenotype of progressive weakness of the shoulder and hip girdle muscles. While the individual genetic mutations are rare, as a cohort, LGMDs are one of the four most common muscular dystrophies.

Myotonic Dystrophy Type 2 (DM2) is a more recently discovered, rare type of myotonic dystrophy. DM2 is inherited in an autosomal dominant pattern and is caused by an unstable CCTG expansion. DM2 affects the muscles and other body systems (e.g. heart and eyes).

Pompe disease is a rare, multisystemic, hereditary disease which is caused by pathogenic variations in the GAA gene. Late onset Pompe disease (LOPD) refers to cases in which hypertrophic cardiomyopathy did not manifest or was not diagnosed at or under the age of 1 year. LOPD is characterized by skeletal muscle weakness which causes mobility problems and impacts the respiratory system.

The overall goal of this project is to extend prior observational studies conducted within the GRASP LGMD network to define the key phenotypes as measured by standard clinical outcome assessments (COAs) for multiple rare types of muscular dystrophy to hasten therapeutic development.

Первичные конечные точки

• To explore the suitability and feasibility of the North Star Assessment for LGMD (NSAD) in the muscular dystrophies [Срок оценки: Baseline to 24 months]

Вторичные конечные точки (6)

• To explore the utility of the 100 meter timed test as a clinical outcome assessment in the muscular dystrophies [Срок оценки: Baseline to 24 months]
• To explore the utility of the Performance of the Upper Limb 2.0 (PUL 2.0) assessment as a clinical outcome assessment in the muscular dystrophies [Срок оценки: Baseline to 24 months]
• To explore the utility of spirometry as a clinical outcome assessment in the muscular dystrophies [Срок оценки: Baseline to 24 months]
• To explore the utility of the LGMD-HI questionnaire as a patient-reported outcome measure in the muscular dystrophies. [Срок оценки: Baseline to 24 months]
• To explore the utility of the PROMIS-57 as a patient-reported outcome measure in the muscular dystrophies. [Срок оценки: Baseline to 24 months]
• To explore the utility of the Domain Delta as a patient-reported outcome measure in the muscular dystrophies [Срок оценки: Baseline to 24 months]

Критерии участия

Критерии включения

• Age between 6-50 years at enrollment
• Clinically affected (defined as weakness on bedside evaluation in a pattern consistent with proximal weakness)
• Genetic confirmation of a LGMD, DM2, or LOPD
• FVC above 30% of predicted

Критерии исключения

• Any other illness that would interfere with the ability to undergo safe testing or would interfere with interpretation of the results in the opinion of the site investigator
• Participation in a clinical trial receiving an investigational product

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

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

США · 1 центр

• Virginia Commonwealth University — Richmond

Публикации

• van de Velde NM, Hooijmans MT, Sardjoe Mishre ASD, Keene KR, Koeks Z, Veeger TTJ, Alleman I, van Zwet EW, Beenakker JM, Verschuuren JJGM, Kan HE, Niks EH. Selection Approach to Identify the Optimal Biomarker Using Quantitative Muscle MRI and Functional Assessments in Becker Muscular Dystrophy. Neurology. 2021 Aug 3;97(5):e513-e522. doi: 10.1212/WNL.0000000000012233. Epub 2021 Jun 23. PMID 34162720
• Mendell JR, Al-Zaidy S, Shell R, Arnold WD, Rodino-Klapac LR, Prior TW, Lowes L, Alfano L, Berry K, Church K, Kissel JT, Nagendran S, L'Italien J, Sproule DM, Wells C, Cardenas JA, Heitzer MD, Kaspar A, Corcoran S, Braun L, Likhite S, Miranda C, Meyer K, Foust KD, Burghes AHM, Kaspar BK. Single-Dose Gene-Replacement Therapy for Spinal Muscular Atrophy. N Engl J Med. 2017 Nov 2;377(18):1713-1722. d PMID 29091557
• Pozsgai ER, Griffin DA, Heller KN, Mendell JR, Rodino-Klapac LR. Systemic AAV-Mediated beta-Sarcoglycan Delivery Targeting Cardiac and Skeletal Muscle Ameliorates Histological and Functional Deficits in LGMD2E Mice. Mol Ther. 2017 Apr 5;25(4):855-869. doi: 10.1016/j.ymthe.2017.02.013. Epub 2017 Mar 9. PMID 28284983
• Mendell JR, Rodino-Klapac LR, Rosales XQ, Coley BD, Galloway G, Lewis S, Malik V, Shilling C, Byrne BJ, Conlon T, Campbell KJ, Bremer WG, Taylor LE, Flanigan KM, Gastier-Foster JM, Astbury C, Kota J, Sahenk Z, Walker CM, Clark KR. Sustained alpha-sarcoglycan gene expression after gene transfer in limb-girdle muscular dystrophy, type 2D. Ann Neurol. 2010 Nov;68(5):629-38. doi: 10.1002/ana.22251. PMID 21031578
• Potter RA, Griffin DA, Sondergaard PC, Johnson RW, Pozsgai ER, Heller KN, Peterson EL, Lehtimaki KK, Windish HP, Mittal PJ, Albrecht DE, Mendell JR, Rodino-Klapac LR. Systemic Delivery of Dysferlin Overlap Vectors Provides Long-Term Gene Expression and Functional Improvement for Dysferlinopathy. Hum Gene Ther. 2018 Jul;29(7):749-762. doi: 10.1089/hum.2017.062. Epub 2017 Jul 13. PMID 28707952
• Mayhew AG, Cano SJ, Scott E, Eagle M, Bushby K, Manzur A, Muntoni F; North Star Clinical Network for Neuromuscular Disease. Detecting meaningful change using the North Star Ambulatory Assessment in Duchenne muscular dystrophy. Dev Med Child Neurol. 2013 Nov;55(11):1046-52. doi: 10.1111/dmcn.12220. Epub 2013 Aug 5. PMID 23909763
• Harris E, Bladen CL, Mayhew A, James M, Bettinson K, Moore U, Smith FE, Rufibach L, Cnaan A, Bharucha-Goebel DX, Blamire AM, Bravver E, Carlier PG, Day JW, Diaz-Manera J, Eagle M, Grieben U, Harms M, Jones KJ, Lochmuller H, Mendell JR, Mori-Yoshimura M, Paradas C, Pegoraro E, Pestronk A, Salort-Campana E, Schreiber-Katz O, Semplicini C, Spuler S, Stojkovic T, Straub V, Takeda S, Rocha CT, Walter M PMID 27602406
• James MK, Alfano LN, Muni-Lofra R, Reash NF, Sodhi J, Iammarino MA, Moat D, Shannon K, McCallum M, Richardson M, Eagle M, Straub V, Marini-Bettolo C, Lowes LP, Mayhew AG. Validation of the North Star Assessment for Limb-Girdle Type Muscular Dystrophies. Phys Ther. 2022 Oct 6;102(10):pzac113. doi: 10.1093/ptj/pzac113. PMID 35932452

Идентификаторы

NCT: NCT05989620 · HM20027839

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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