Clinical trial NCT04583917: Brain Involvement in Dystrophinopathies Part 1
Official title: Brain INvolvement in Dystrophinopathies (BIND): Deep Functional Phenotyping of Duchenne Muscular Dystrophy and Becker Muscular Dystrophy Patients (WP5) Part 1: a Multicentre Online Phenotyping and Neurobehavioural Data Collection Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Duchenne Muscular Dystrophy
Becker Muscular Dystrophy
Lead sponsor: Great Ormond Street Hospital for Children NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: Newcastle-upon-Tyne Hospitals NHS Trust
name: Leiden University Medical Center
name: Stichting Kempenhaeghe
name: Region Hovedstadens Apotek
name: Institut Necker Enfants Malades
name: Catholic University of the Sacred Heart
name: Università degli Studi di Ferrara
name: Universidad Complutense de Madrid
First posted: 2020-10-12
Enrollment: 377
Sex: MALE
Minimum age (years): 5
Maximum age (years): 50
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients will be those followed in the two neuromuscular centres located in London and Newcastle; via the UK Clinical North Star network, the BIND website and the UK advocacy groups MDUK, Action Duchenne and Duchenne UK. A similar recruitment process will take place in the other EU countries, according to local regulations and after having obtained the relevant local ethical approval.

Brief summary: The objective of this study is to collect data from a large cohort of individuals with DMD and BMD focusing on the neurobehavioural aspects of these conditions and their correlation to the location of the DMD gene mutation.

Detailed description: Intellectual disability and neurobehavioural comorbidities affect at least 50% of the individuals with Duchenne muscular dystrophy (DMD), which, although a rare genetic disease, is the most common form of muscular dystrophy in childhood. Several studies have documented that 25% of the DMD population has intellectual disability with recent studies suggesting that autism and clinically relevant hyperactivity affects 20% and 25% of DMD boys respectively. A milder allelic variant, named Becker muscular dystrophy (BMD), has similar prevalence in the population and is also associated with variable degrees of central nervous system (CNS) comorbidities, which however have been less well defined.

The investigators will address these deficiencies in a large multicentre study funded by the European Commission (EU H2020) involving 6 countries (Denmark; The Netherlands; France; Spain; Italy and UK) with the largest European neuromuscular centres and advocacy groups. The aim will be to study the neurobehavioural aspects of DMD and BMD as well as their correlation to the genotype. This study will involve male participants with DMD aged 5-17 years and with BMD aged 5-50 years. It will comprise of online questionnaires that will be completed either by a parent of a participant \<17 years or an adult participant. The questionnaires take approximately 70 minutes to complete, however this can be done in multiple sittings. Currently there is a lack of information to assist the prognosis of CNS comorbidities, as existing databases and registries typically focus on the motor milestones and physical disability of these patients. There is therefore, an urgent need to present the course and outcomes in DMD and BMD patients with a wide range of DMD mutations, to provide information at the point of diagnosis and onwards for families, clinicians and service providers. It will also assist in paving the way to greater biological understanding and personalization of interventions.

Eligibility criteria: Inclusion Criteria:

For DMD patients:

* Male
* age 5-17 years
* genetically-proven diagnosis of DMD
* genetic mutation that abrogates expression of Dp427 alone (assigned in DMD Group 1: Dp427-/Dp140+) or both Dp427 and Dp140 (assigned to DMD Group 2: Dp427-/Dp140-); or all isoforms (assigned to DMD group 3)

For BMD patients:

* age 5-50 years
* genetically-proven diagnosis of BMD
* genetic mutation that decreases expression of Dp427 alone (assigned to BMD Group 1), of both Dp427 and Dp140 (assigned to BMD Group 2), or of all the isoforms (assigned to BMD group 3).

Exclusion Criteria:

* Lack of a molecular diagnosis of DMD or BMD
* Mutation falls outside the regions of interest
* A severe co-morbidity or planned surgical intervention within 6 months from the study which could interfere with the well-being of the participant

Primary outcomes:
measure: CNS Comorbidity Pheotyping
timeFrame: 90 minutes
Secondary outcomes:
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Copenhagen Neuromuscular Center
city: Paris
country: France
facility: Imagine Institut Des Maladies Genetiques Necker Enfants Malades Fondation
city: Rome
country: Italy
facility: Universita Cattolica Del Sacro Cuore
city: Heeze
country: Netherlands
facility: Stichting Kempenhaeghe
city: Madrid
country: Spain
facility: Universidad Complutense de Madrid
city: London
country: United Kingdom
facility: GOSH/UCL
city: Newcastle
country: United Kingdom
facility: University of Newcastle Upon Tyne
Study officials:
affiliation: University College, London
name: Francesco Muntoni
role: PRINCIPAL_INVESTIGATOR
References: