Clinical Outcome Study for Dysferlinopathy

NCT01676077 | Unknown DMC

• 1 other identifier: 85750
• Study Type: observational
• Target: 200
• Locations: 9 countries
• Sites: 16

Brief Summary

The "Clinical Outcome Study for Dysferlinopathy" is being performed in centres in Europe (UK- Newcastle; Spain- Barcelona, Sevilla; San Sebastian;Denmark, Copenhagen, Italy- Padova; France- Paris,), USA (Charlotte, NC; Columbus, OH; St.Louis, MO, Stanford CA, Irvine CA and Columbia NY), Chile (Santiago) Japan (Tokyo) and South Korea (Pusan). Oversight is provided by Newcastle upon Tyne Hospitals Trust. Funding for this study is being provided by the Jain Foundation, a non-profit foundation dedicated to finding therapies for dysferlinopathies(LGMD2b/Miyoshi). The aim of this "Clinical Outcome Study" is to determine the clinical outcome measures required for future clinical trials, characterize the disease progression of dysferlinopathy and collect biological samples for the identification of disease markers that are needed to non-invasively monitor the disease during clinical trials. Without this information, effective clinical trials cannot be performed. This study is recruiting a large number of genetically confirmed dysferlinopathy patients aged 10 years or older, who are ambulant or non-ambulant. The study has reopened for a further two years (COS2). Participants will be assessed at 4 further visits over 2 years via medical, physiotherapy, and MRI/MRS assessments, as well as standard blood tests. Optionally, the participants can donate blood samples and a skin sample for use in the identification of disease markers and other approved research. There is a sub-study running in MRI at selected sites.

Conditions

Dysferlinopathy; LGMD2B Now Classified as LGMDR2; Miyoshi Myopathy

Keywords

LGMD2B/ LGMDR9; Miyoshi Myopathy; Dysferlin; Dysferlinopathy; Limb Girdle muscular dystrophy type 2b; Muscular Dystrophy

Outcome Measures

Primary Outcomes (1)

• North Star assessment for limb girdle-type muscular dystrophies (NSAD)

  A functional scale that will be used to measure motor performance in individuals with LGMD

  24 months

Study Arms (1)

Patients with a genetically confirmed dysferlinopathy

Eligibility Criteria

• Age: 10 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

A diagnosis of Limb Girdle Muscular Dystrophy type 2B (LGMD2B/ LGMDR2), Miyoshi myopathy, or any other clinical diagnosis associated with dysferlinopathies

You may qualify if:

• \- Confirmed diagnosis of dysferlinopathy proven by a) two (predicted) pathogenic dysferlin mutations, b) one (predicted) pathogenic dysferlin mutation and absent dysferlin protein on muscle immunoblot, or c) one (predicted) pathogenic dysferlin mutation and dysferlin protein level ≤20% of normal level determined by blood monocyte testing. Mutations will be checked for pathogenicity via the UMD bioinformatics tools and and by checking the literature and mutation /variant databases.
• NOTE: Contact Sarah Shira at the Jain Foundation for help with diagnosis at +1 425 882 1492
• Ambulant with or without aids; or full-time wheelchair user, i.e. non-ambulant; with the ratio 2:1 between recruited ambulant and recruited non-ambulant patients.
• All ages ≥ 10 years of age.
• Ability to perform assessments (there will be different assessments for ambulant and non-ambulant patients).
• Ability to attend scheduled investigations.
• Informed consent to participate in the clinical outcome study.
• NOTE: Funds are available to cover necessary hotel stays and travel costs to the study centres for the participant and a helper (if needed).

You may not qualify if:

• Known current or planned medical or other interventions that might interfere with the possibility to undertake the planned tests.
• Other concomitant pathology that in the view of the investigator would jeopardise the ability to take part in the protocol.

Sponsors & Collaborators

• Newcastle-upon-Tyne Hospitals NHS Trust: lead
• Jain Foundation: collaborator

Study Sites (16)

UC Irvine

Orange, California, United States

Location

Stanford University Medical Center

Palo Alto, California, 944305, United States

Location

Neurology & Pathology, Washington University, School of Medicine in St Louis

St Louis, Missouri, 63110, United States

Location

Columbia University Medical Centre

New York, New York, United States

Location

Carolinas Medical Center, Neuroscience & Spine Institute, Dept of Neurology

Charlotte, North Carolina, 28207, United States

Location

Neuromuscular Center at the Research Institute of Nationwide Children's Hospital

Columbus, Ohio, 43230, United States

Location

Clinica Davila

Santiago, Chile

Location

Rigshospitalet Neuromusculaer Klinik

Copenhagen, Denmark

Location

Institut de Myologie

Paris, 75013, France

Location

Department of Neurosciences, University of Padova

Padua, 35128, Italy

Location

National Center of Neurology and Psychiatry

Kodaira, Tokyo, 187-8551, Japan

Location

Pusan National University Hospital

Busan, South Korea

Location

Hospital Sant Pau, Neurology Department

Barcelona, 08041, Spain

Location

Hospital Universitario Donostia

San Sebastián, Spain

Location

Hospital Universitario Virgen del Rocio, IBiS, Neurology Department

Seville, 41013, Spain

Location

Institute of Translational and Clinical Research, Newcastle University, International Centre for Life

Newcastle upon Tyne, NE1 3BZ, United Kingdom

Location

Related Publications (3)

• Moore U, Jacobs M, James MK, Mayhew AG, Fernandez-Torron R, Feng J, Cnaan A, Eagle M, Bettinson K, Rufibach LE, Lofra RM, Blamire AM, Carlier PG, Mittal P, Lowes LP, Alfano L, Rose K, Duong T, Berry KM, Montiel-Morillo E, Pedrosa-Hernandez I, Holsten S, Sanjak M, Ashida A, Sakamoto C, Tateishi T, Yajima H, Canal A, Ollivier G, Decostre V, Mendez JB, Sanchez-Aguilera Praxedes N, Thiele S, Siener C, Shierbecker J, Florence JM, Vandevelde B, DeWolf B, Hutchence M, Gee R, Prugel J, Maron E, Hilsden H, Lochmuller H, Grieben U, Spuler S, Tesi Rocha C, Day JW, Jones KJ, Bharucha-Goebel DX, Salort-Campana E, Harms M, Pestronk A, Krause S, Schreiber-Katz O, Walter MC, Paradas C, Hogrel JY, Stojkovic T, Takeda S, Mori-Yoshimura M, Bravver E, Sparks S, Diaz-Manera J, Bello L, Semplicini C, Pegoraro E, Mendell JR, Bushby K, Straub V; Jain COS Consortium. Assessment of disease progression in dysferlinopathy: A 1-year cohort study. Neurology. 2019 Jan 28;92(5):e461-e474. doi: 10.1212/WNL.0000000000006858.

  PMID: 30626655 DERIVED

• Diaz-Manera J, Fernandez-Torron R, LLauger J, James MK, Mayhew A, Smith FE, Moore UR, Blamire AM, Carlier PG, Rufibach L, Mittal P, Eagle M, Jacobs M, Hodgson T, Wallace D, Ward L, Smith M, Stramare R, Rampado A, Sato N, Tamaru T, Harwick B, Rico Gala S, Turk S, Coppenrath EM, Foster G, Bendahan D, Le Fur Y, Fricke ST, Otero H, Foster SL, Peduto A, Sawyer AM, Hilsden H, Lochmuller H, Grieben U, Spuler S, Tesi Rocha C, Day JW, Jones KJ, Bharucha-Goebel DX, Salort-Campana E, Harms M, Pestronk A, Krause S, Schreiber-Katz O, Walter MC, Paradas C, Hogrel JY, Stojkovic T, Takeda S, Mori-Yoshimura M, Bravver E, Sparks S, Bello L, Semplicini C, Pegoraro E, Mendell JR, Bushby K, Straub V; Jain COS Consortium. Muscle MRI in patients with dysferlinopathy: pattern recognition and implications for clinical trials. J Neurol Neurosurg Psychiatry. 2018 Oct;89(10):1071-1081. doi: 10.1136/jnnp-2017-317488. Epub 2018 May 7.

  PMID: 29735511 DERIVED

• Moore UR, Jacobs M, Fernandez-Torron R, Jang J, James MK, Mayhew A, Rufibach L, Mittal P, Eagle M, Cnaan A, Carlier PG, Blamire A, Hilsden H, Lochmuller H, Grieben U, Spuler S, Tesi Rocha C, Day JW, Jones KJ, Bharucha-Goebel DX, Salort-Campana E, Harms M, Pestronk A, Krause S, Schreiber-Katz O, Walter MC, Paradas C, Hogrel JY, Stojkovic T, Takeda S, Mori-Yoshimura M, Bravver E, Sparks S, Diaz-Manera J, Bello L, Semplicini C, Pegoraro E, Mendell JR, Bushby K, Straub V. Teenage exercise is associated with earlier symptom onset in dysferlinopathy: a retrospective cohort study. J Neurol Neurosurg Psychiatry. 2018 Nov;89(11):1224-1226. doi: 10.1136/jnnp-2017-317329. Epub 2018 Jan 29. No abstract available.

  PMID: 29378789 DERIVED

Related Links

• This study is fully funded by the Jain Foundation, a non-profit foundation whose mission is to cure muscular dystrophies caused by dysferlin protein deficiency.
• All information for this study can be found on the study website (www.dysferlinoutcomestudy.org), including contact details and participating sites

Biospecimen

Retention: SAMPLES WITH DNA

Serum, Plasma, DNA, RNA, Skin fibroblasts, Urine

MeSH Terms

Conditions

Dysferlinopathy; Miyoshi myopathy; Limb-girdle muscular dystrophy, type 2B; Muscular Dystrophies

Condition Hierarchy (Ancestors)

Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Volker Straub

  Newcastle University

  PRINCIPAL INVESTIGATOR

• Meredith K James

  Newcastle University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 28, 2012
• First Posted: August 30, 2012
• Study Start: September 1, 2012
• Primary Completion: March 1, 2024
• Study Completion: March 1, 2024
• Last Updated: July 26, 2022

Record last verified: 2022-07

Locations

CL (1); KR (1); DK (1); FR (1); GB (1); US (6); IT (1); JP (1); ES (3)