Brain Involvement in Dystrophinopathies Part 2

NCT ID: NCT04668716

Last Updated: 2024-07-22

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 339 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2021-10-11
• Study Completion Date: 2024-06-30

Brief Summary

The objective of this study is to understand the relationship between DMD and BMD brain comorbidities, and the location of the gene mutation which causes the disease.

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.

We will address this knowledge gap in a large multicentre study funded by the European Commission H2020 programme, 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, who will complete a battery of cognitive and behavioural assessments. The objective of this study is to deep phenotype a cohort of 270 individuals with DMD and BMD, focussing on the cognitive and neurobehavioural aspects of these conditions. A sub-groups of patients will also undergo magnetic resonance imaging to investigate brain structure, volumetric features, perfusion, functional connectivity and metabolism. This information will then be correlated to the location of the underlying DMD gene mutation. The brain imaging part is also going to involve age and sex-matched controls.

While there have been major improvement on the definition of the genetic basis of the skeletal aspects of dystrophinopathies and their correlation to the DMD genotype, our knowledge on the spectrum of lifespan CNS comorbidities and the precise genotype / phenotype correlations in patients with different DMD mutations is still limited. A study looking into the association between different dystrophin isoforms and different CNS manifestations would therefore offer a unique opportunity to unravel the role of specific dystrophin isoforms and the associated circuitries in brain function.

Conditions

Duchenne Muscular Dystrophy; Becker Muscular Dystrophy

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: CROSS_SECTIONAL

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).

For MRI controls:

• Male
• age 5-50 years

Exclusion Criteria

For DMD and BMD patients:

• 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

For MRI controls:

• any muscle disease
• a brain disorder (such as severe brain concussion in past history, congenital brain anomalies, epilepsy)

• Claustrophobia
• Pacemakers and defibrillators
• Nerve stimulators
• Intracranial clips
• Intraorbital or intraocular metallic fragments
• Cochlear implants
• Ferromagnetic implants (e.g. thoracic implant for scoliosis)
• Inability to lie supine during less than 45 minutes
• not having a general practitioner
• severe learning disability which will require a general anaesthetic

• Minimum Eligible Age: 5 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Newcastle-upon-Tyne Hospitals NHS Trust

OTHER

Sponsor Role: collaborator

Leiden University Medical Center

OTHER

Sponsor Role: collaborator

Stichting Kempenhaeghe

UNKNOWN

Sponsor Role: collaborator

Region Hovedstadens Apotek

OTHER_GOV

Sponsor Role: collaborator

Institut Necker Enfants Malades

OTHER

Sponsor Role: collaborator

Catholic University of the Sacred Heart

OTHER

Sponsor Role: collaborator

Università degli Studi di Ferrara

OTHER

Sponsor Role: collaborator

Universidad Complutense de Madrid

OTHER

Sponsor Role: collaborator

Great Ormond Street Hospital for Children NHS Foundation Trust

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Copenhagen Neuromuscular Center

Copenhagen, , Denmark

Imagine Institut Des Maladies Genetiques Necker Enfants Malades Fondation

Paris, , France

Universita Cattolica Del Sacro Cuore

Rome, , Italy

STICHTING KEMPENHAEGHE/Leiden University Medical Center

Heeze, , Netherlands

Universidad Complutense de Madrid

Madrid, , Spain

UCL/GOSH

London, , United Kingdom

University of Newcastle Upon Tyne

Newcastle, , United Kingdom

Countries

Denmark; France; Italy; Netherlands; Spain; United Kingdom

Related Links

http://bindproject.eu/

BIND: Brain Involvement in Dystrophinopathies study website

Other Identifiers

20NM35

Identifier Type: -

Identifier Source: org_study_id