Clinical trial NCT05989620: Long-Term Development of Muscular Dystrophy Outcome Assessments
Official title: Long-Term Development of Muscular Dystrophy Outcome Assessments (GRASP-01-005)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: LGMD1B
LGMD1C
LGMD1D
LGMD1E
LGMD1F
LGMD1G
LGMD1H
LGMD2A
LGMD2B
LGMD2C
LGMD2D
LGMD2E
LGMD2F
LGMD2G
LGMD2I
LGMD2J
LGMD2K
LGMD2L
LGMD2M
LGMD2N
LGMD2O
LGMD2P
LGMD2Q
LGMD2S
LGMD2T
LGMD2U
LGMD2W
LGMD2X
LGMD2Y
Keywords: Muscular Dystrophy
Myotonic Dystrophy
Limb Girdle Muscular Dystrophy
LGMD
LOPD
Late Onset Pompe Disease
Lead sponsor: Virginia Commonwealth University
Sponsor class: OTHER
Collaborators: name: Muscular Dystrophy Association
First posted: 2023-08-14
Enrollment: 1000
Sex: ALL
Minimum age (years): 6
Maximum age (years): 50
Standard ages: CHILD
ADULT
Observational model: COHORT
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study seeks to enroll ambulatory individuals aged 6-50 years at enrollment who are clinically affected by LGMD, DM2, or LOPD.

Brief summary: 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).

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

1. 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
2. Participation in a clinical trial receiving an investigational product

Primary outcomes:
measure: To explore the suitability and feasibility of the North Star Assessment for LGMD (NSAD) in the muscular dystrophies
timeFrame: Baseline to 24 months
Secondary outcomes:
measure: To explore the utility of the 100 meter timed test as a clinical outcome assessment in the muscular dystrophies
timeFrame: Baseline to 24 months
measure: 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
timeFrame: Baseline to 24 months
measure: To explore the utility of spirometry as a clinical outcome assessment in the muscular dystrophies
timeFrame: Baseline to 24 months
measure: To explore the utility of the LGMD-HI questionnaire as a patient-reported outcome measure in the muscular dystrophies.
timeFrame: Baseline to 24 months
measure: To explore the utility of the PROMIS-57 as a patient-reported outcome measure in the muscular dystrophies.
timeFrame: Baseline to 24 months
measure: To explore the utility of the Domain Delta as a patient-reported outcome measure in the muscular dystrophies
timeFrame: Baseline to 24 months
Other outcomes:
Locations:
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
Study officials:
affiliation: Virginia Commonwealth University
name: Nicholas Johnson, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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. doi: 10.1056/NEJMoa1706198.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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 MC, Bushby K; Jain COS Consortium. The Clinical Outcome Study for dysferlinopathy: An international multicenter study. Neurol Genet. 2016 Aug 4;2(4):e89. doi: 10.1212/NXG.0000000000000089. eCollection 2016 Aug.
citation: 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.
citation: Hunter M, Heatwole C, Wicklund M, Weihl CC, Mozaffar T, Statland JM, Johnson NE. Limb-girdle muscular dystrophy: A perspective from adult patients on what matters most. Muscle Nerve. 2019 Oct;60(4):419-424. doi: 10.1002/mus.26636. Epub 2019 Jul 24.
citation: Arrigoni F, De Luca A, Velardo D, Magri F, Gandossini S, Russo A, Froeling M, Bertoldo A, Leemans A, Bresolin N, D'angelo G. Multiparametric quantitative MRI assessment of thigh muscles in limb-girdle muscular dystrophy 2A and 2B. Muscle Nerve. 2018 Oct;58(4):550-558. doi: 10.1002/mus.26189. Epub 2018 Aug 22.
citation: Willis TA, Hollingsworth KG, Coombs A, Sveen ML, Andersen S, Stojkovic T, Eagle M, Mayhew A, de Sousa PL, Dewar L, Morrow JM, Sinclair CD, Thornton JS, Bushby K, Lochmuller H, Hanna MG, Hogrel JY, Carlier PG, Vissing J, Straub V. Quantitative magnetic resonance imaging in limb-girdle muscular dystrophy 2I: a multinational cross-sectional study. PLoS One. 2014 Feb 28;9(2):e90377. doi: 10.1371/journal.pone.0090377. eCollection 2014.
citation: Murphy AP, Morrow J, Dahlqvist JR, Stojkovic T, Willis TA, Sinclair CDJ, Wastling S, Yousry T, Hanna MS, James MK, Mayhew A, Eagle M, Lee LE, Hogrel JY, Carlier PG, Thornton JS, Vissing J, Hollingsworth KG, Straub V. Natural history of limb girdle muscular dystrophy R9 over 6 years: searching for trial endpoints. Ann Clin Transl Neurol. 2019 May 16;6(6):1033-1045. doi: 10.1002/acn3.774. eCollection 2019 Jun.
citation: Reyngoudt H, Marty B, Boisserie JM, Le Louer J, Koumako C, Baudin PY, Wong B, Stojkovic T, Behin A, Gidaro T, Allenbach Y, Benveniste O, Servais L, Carlier PG. Global versus individual muscle segmentation to assess quantitative MRI-based fat fraction changes in neuromuscular diseases. Eur Radiol. 2021 Jun;31(6):4264-4276. doi: 10.1007/s00330-020-07487-0. Epub 2020 Nov 21.
citation: Reyngoudt H, Smith FE, Caldas de Almeida Araujo E, Wilson I, Fernandez-Torron R, James MK, Moore UR, Diaz-Manera J, Marty B, Azzabou N, Gordish H, Rufibach L, Hodgson T, Wallace D, Ward L, Boisserie JM, Le Louer J, Hilsden H, Sutherland H, Canal A, Hogrel JY, Jacobs M, Stojkovic T, Bushby K, Mayhew A; Jain Clinical Outcome Study for Dysferlinopathy consortium; Straub V, Carlier PG, Blamire AM. Three-year quantitative magnetic resonance imaging and phosphorus magnetic resonance spectroscopy study in lower limb muscle in dysferlinopathy. J Cachexia Sarcopenia Muscle. 2022 Jun;13(3):1850-1863. doi: 10.1002/jcsm.12987. Epub 2022 Apr 3.
citation: Barnard AM, Willcocks RJ, Finanger EL, Daniels MJ, Triplett WT, Rooney WD, Lott DJ, Forbes SC, Wang DJ, Senesac CR, Harrington AT, Finkel RS, Russman BS, Byrne BJ, Tennekoon GI, Walter GA, Sweeney HL, Vandenborne K. Skeletal muscle magnetic resonance biomarkers correlate with function and sentinel events in Duchenne muscular dystrophy. PLoS One. 2018 Mar 19;13(3):e0194283. doi: 10.1371/journal.pone.0194283. eCollection 2018.
citation: Willcocks RJ, Arpan IA, Forbes SC, Lott DJ, Senesac CR, Senesac E, Deol J, Triplett WT, Baligand C, Daniels MJ, Sweeney HL, Walter GA, Vandenborne K. Longitudinal measurements of MRI-T2 in boys with Duchenne muscular dystrophy: effects of age and disease progression. Neuromuscul Disord. 2014 May;24(5):393-401. doi: 10.1016/j.nmd.2013.12.012. Epub 2014 Jan 11.
citation: Burakiewicz J, Sinclair CDJ, Fischer D, Walter GA, Kan HE, Hollingsworth KG. Quantifying fat replacement of muscle by quantitative MRI in muscular dystrophy. J Neurol. 2017 Oct;264(10):2053-2067. doi: 10.1007/s00415-017-8547-3. Epub 2017 Jul 1.
citation: Willcocks RJ, Rooney WD, Triplett WT, Forbes SC, Lott DJ, Senesac CR, Daniels MJ, Wang DJ, Harrington AT, Tennekoon GI, Russman BS, Finanger EL, Byrne BJ, Finkel RS, Walter GA, Sweeney HL, Vandenborne K. Multicenter prospective longitudinal study of magnetic resonance biomarkers in a large duchenne muscular dystrophy cohort. Ann Neurol. 2016 Apr;79(4):535-47. doi: 10.1002/ana.24599. Epub 2016 Feb 19.
citation: Comi GP, Niks EH, Cinnante CM, Kan HE, Vandenborne K, Willcocks RJ, Velardo D, Ripolone M, van Benthem JJ, van de Velde NM, Nava S, Ambrosoli L, Cazzaniga S, Bettica PU. Characterization of patients with Becker muscular dystrophy by histology, magnetic resonance imaging, function, and strength assessments. Muscle Nerve. 2022 Mar;65(3):326-333. doi: 10.1002/mus.27475. Epub 2021 Dec 30.
citation: Batra A, Lott DJ, Willcocks R, Forbes SC, Triplett W, Dastgir J, Yun P, Reghan Foley A, Bonnemann CG, Vandenborne K, Walter GA. Lower Extremity Muscle Involvement in the Intermediate and Bethlem Myopathy Forms of COL6-Related Dystrophy and Duchenne Muscular Dystrophy: A Cross-Sectional Study. J Neuromuscul Dis. 2020;7(4):407-417. doi: 10.3233/JND-190457.
citation: Pane M, Coratti G, Brogna C, Mazzone ES, Mayhew A, Fanelli L, Messina S, D'Amico A, Catteruccia M, Scutifero M, Frosini S, Lanzillotta V, Colia G, Cavallaro F, Rolle E, De Sanctis R, Forcina N, Petillo R, Barp A, Gardani A, Pini A, Monaco G, D'Angelo MG, Zanin R, Vita GL, Bruno C, Mongini T, Ricci F, Pegoraro E, Bello L, Berardinelli A, Battini R, Sansone V, Albamonte E, Baranello G, Bertini E, Politano L, Sormani MP, Mercuri E. Upper limb function in Duchenne muscular dystrophy: 24 month longitudinal data. PLoS One. 2018 Jun 20;13(6):e0199223. doi: 10.1371/journal.pone.0199223. eCollection 2018.