Outcome Measures in Duchenne Muscular Dystrophy: A Natural History Study

NCT02780492 | Completed

• 1 other identifier: 12/0096 (09DN17)
• Study Type: observational
• Target: 35
• Locations: 3 countries
• Sites: 5

Brief Summary

Novel emerging therapies for Duchenne Muscular Dystrophy (DMD) require a deeper understanding of DMD natural history. This study aim to assess the natural history of DMD through a composite assessment tool capable of capturing disease progression linking ambulant and non-ambulant phases of the disease.

Conditions

Duchenne Muscular Dystrophy

Keywords

Duchenne muscular dystrophy; Natural history; Outcome measures; North Star Ambulatory Assessment (NSAA); 6 minute walk distance (6MWD); Myoset; Exon skipping

Outcome Measures

Primary Outcomes (1)

• Disease progression

  Evaluate disease progression from ambulant to non-ambulant patients through a composite assessment tool

  up to 4 years

Study Arms (3)

Ambulant patients

A set of assessment tools (blood analyses, functional, respiratory, quality of life questionnaires, Dexa scan, MRI) will be performed.

Other: Set of assessment tools

Non-ambulant patients

A set of assessment tools (blood analyses, functional, respiratory, quality of life questionnaires, Dexa scan, MRI) will be performed.

Other: Set of assessment tools

Healthy volunteers and Disease controls

A set of assessment tools (upper limb function tests, MRI, blood analyses) will be performed

Other: Set of assessment tools

Interventions

Set of assessment tools OTHER

Ambulant patients; Healthy volunteers and Disease controls; Non-ambulant patients

Eligibility Criteria

• Age: 5 Years - 18 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Patients with Duchenne muscular dystrophy (DMD) recruited across 5 specialised neuromuscular centres (London, Newcastle, Paris, Leiden, Nijmegen)

You may qualify if:

• For non-ambulant patients:
• Children and teenagers aged between 5 and 18 years with DMD, who have lost the ability to walk 10 meters with no support
• The diagnosis of DMD must be documented by genetic testing. If a muscle biopsy is available, it should contain less than 10% of revertant fibres
• Patients should have deletions amenable of skipping of exons 51 or 53 or 45 or 44 or 46 or 50 or 52
• Patients should be capable of sitting upright in a wheelchair for at least an hour
• Patients should be stable from a respiratory point of view. Artificial ventilation with either Bipap or tracheostomy is not a contraindication to the study.
• Informed consent signed by a parent/legal guardian (or by the patient if 16 years of age).
• For ambulant patients:
• Ambulant children from 5 years old and teenagers with DMD, and potential candidates for future genetic therapies with antisense oligomer (AO) exon skipping
• The diagnosis of DMD must be documented by MLPA or a standard genetic test for the disorder, genotypically confirmed to have an out-of-frame deletion(s) that could be corrected by skipping exon 51 or 53 or 45 or 44 or 46 or 50 or 52
• If a muscle biopsy is available less than 10% revertant fibres
• Ability to walk independently for at least 75 meters in 6 minutes at recruitment.
• Patients should receive the standard of care for DMD as recommended by the NorthStar UK and TREAT-NMD (i.e.: on glucocorticoids treatment)
• Sufficiently preserved pulmonary function (FVC \>30%) and absence of symptoms of cardiac failure
• Informed consent signed by a parent/legal guardian (or by the patient if 16 years of age)

You may not qualify if:

• For non-ambulant patients:
• Patients with severe intellectual impairment, who would be unable to cooperate with examination
• Patients/families the investigators anticipate may have emotional/ psychological problems if recruited into a natural history study
• Symptomatic cardiac failure
• Recent (\< 6 months) upper limb surgery or trauma
• Anticipated surgery for anytime during the duration of the study
• For the MRI sub-study, patients with metal/metallic surgically inserted equipment incompatible with MRI scan will be excluded as well as patients suffering from claustrophobia.
• For ambulant patients:
• Patients with severe intellectual impairment, who would be unable to cooperate with examination
• Patients/families the investigators anticipate may have emotional/ psychological problems if recruited into a natural history study
• Recent surgery or anticipated for anytime during the duration of the study
• For the MRI sub-study, patients with metal/metallic surgically inserted equipment incompatible with MRI scan will be excluded as well as patients suffering from claustrophobia.
• For healthy volunteers and disease controls
• Patients with severe intellectual impairment, who would be unable to cooperate with examination
• Patients/families the investigators anticipate may have emotional/ psychological problems if recruited into a natural history study

Sponsors & Collaborators

• University College, London: lead
• Association Française contre les Myopathies (AFM), Paris: collaborator
• University of Newcastle Upon-Tyne: collaborator
• Groupe Hospitalier Pitie-Salpetriere: collaborator
• Leiden University Medical Center: collaborator
• Radboud University Medical Center: collaborator

Study Sites (5)

Institut de Myologie, Groupe Hospitalier Pitié Salpêtrière

Paris, France

Location

Leiden University Medical Centre

Leiden, 2300 RC, Netherlands

Location

Radboud University Medical Centre

Nijmegen, 6500 HB, Netherlands

Location

Dubowitz Neuromuscular Centre, UCL-Institute of Child Health

London, WC1N 1EH, United Kingdom

Location

John Walton Muscular Dystrophy Research Centre, Newcastle University

Newcastle, NE1 3BZ, United Kingdom

Location

Related Publications (3)

• Ayyar Gupta V, Pitchforth JM, Domingos J, Ridout D, Iodice M, Rye C, Chesshyre M, Wolfe A, Selby V, Mayhew A, Mazzone ES, Ricotti V, Hogrel JY, Niks EH, de Groot I, Servais L, Straub V, Mercuri E, Manzur AY, Muntoni F; iMDEX Consortium and the U.K. NorthStar Clinical Network. Determining minimal clinically important differences in the North Star Ambulatory Assessment (NSAA) for patients with Duchenne muscular dystrophy. PLoS One. 2023 Apr 26;18(4):e0283669. doi: 10.1371/journal.pone.0283669. eCollection 2023.

  PMID: 37099511 DERIVED

• Trucco F, Ridout D, Domingos J, Maresh K, Chesshyre M, Munot P, Sarkozy A, Robb S, Quinlivan R, Riley M, Wallis C, Chan E, Abel F, De Lucia S, Hogrel JY, Niks EH, de Groot I, Servais L, Straub V, Ricotti V, Manzur A, Muntoni F; UK NorthStar Clinical Network and AFM Network. Genotype-related respiratory progression in Duchenne muscular dystrophy-A multicenter international study. Muscle Nerve. 2022 Jan;65(1):67-74. doi: 10.1002/mus.27427. Epub 2021 Oct 27.

  PMID: 34606104 DERIVED

• Catapano F, Scaglioni D, Maresh K, Ala P, Domingos J, Selby V, Ricotti V, Phillips L, Servais L, Seferian A, Groot I, Krom YD, Voit T, Verschuuren JJGM, Niks EH, Straub V, Morgan J, Muntoni F. Novel free-circulating and extracellular vesicle-derived miRNAs dysregulated in Duchenne muscular dystrophy. Epigenomics. 2020 Nov;12(21):1899-1915. doi: 10.2217/epi-2020-0052. Epub 2020 Nov 20.

  PMID: 33215544 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Single sample suitable for testing for SNP genotyping. This can be either a blood sample, saliva sample or already extracted DNA sample (including stored DNA samples from a laboratory.

MeSH Terms

Conditions

Muscular Dystrophy, Duchenne

Condition Hierarchy (Ancestors)

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

Study Officials

• Francesco Muntoni, PhD

  Dubowitz Neuromuscular Centre, UCL-Institute of Child Health

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: May 19, 2016
• First Posted: May 23, 2016
• Study Start: April 11, 2012
• Primary Completion: April 28, 2022
• Study Completion: April 28, 2022
• Last Updated: January 5, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Up to five years
• Access Criteria: Researchers to obtain permission from the study team.

Locations

FR (1); NL (2); GB (2)