Brain Involvement in Dystrophinopathies Part 2

October 27, 2022 updated by: Great Ormond Street Hospital for Children NHS Foundation Trust

Brain INvolvement in Dystrophinopathies (BIND): Deep Functional Phenotyping of Duchenne Muscular Dystrophy and Becker Muscular Dystrophy Patients (WP5 and WP6) Part 2: a Neurobehavioural and MRI Study

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.

Study Overview

Status

Recruiting

Conditions

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.

Study Type

Observational

Enrollment (Anticipated)

270

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

5 years to 50 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Sampling Method

Non-Probability Sample

Study Population

The investigators will recruit both patients who have completed a related online study (ClinicalTrials.gov Identifier NCT04583917) and patients directly recruited from participating clinics or research settings. These patients will undergo a structured cognitive and neurobehavioural assessment. A subgroup of patients assessed in the research setting will be invited to also attend a second visit involving a magnetic resonance imaging (MRI) scan of the brain.

The investigators aim to recruit 80 participants in the UK and the number of participants in the remaining countries will be 190 patients.

Description

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)

General exclusion criteria for MRI:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Cross-Sectional

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
CNS Comorbidity Phenotyping
Time Frame: 170 minutes
Correlate CNS comorbidity phenotypes with genotype in DMD and BMD patients
170 minutes

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Great Ormond Street Hospital for Children NHS Foundation Trust

Collaborators

Catholic University of the Sacred Heart
Università degli Studi di Ferrara
Universidad Complutense de Madrid
Leiden University Medical Center
Newcastle-upon-Tyne Hospitals NHS Trust
Stichting Kempenhaeghe
Region Hovedstadens Apotek
Institut Necker Enfants Malades

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 11, 2021

Primary Completion (Anticipated)

May 1, 2024

Study Completion (Anticipated)

May 1, 2024

Study Registration Dates

First Submitted

December 9, 2020

First Submitted That Met QC Criteria

December 9, 2020

First Posted (Actual)

December 16, 2020

Study Record Updates

Last Update Posted (Actual)

October 28, 2022

Last Update Submitted That Met QC Criteria

October 27, 2022

Last Verified

October 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 20NM35

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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