Duchenne Muscular DystrophyNCT04668716
Brain Involvement in Dystrophinopathies Part 2
An observational study of Duchenne Muscular Dystrophy and Becker Muscular Dystrophy, run by Great Ormond Street Hospital for Children NHS Foundation Trust at 7 sites in 6 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 5 to 50 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Duchenne Muscular Dystrophy, Becker Muscular Dystrophy
- How many people
- 339 participants
- Where
- 7 sitesin 6 countries
- Study dates
- 11 Oct 2021to 30 Jun 2024
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 to 50 years
- Men only
- Healthy volunteers accepted
- Child, Adult
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.
Who may be able to join
- 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:
Show all 12Show fewer
- 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
Who cannot join
- 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
Show all 18Show fewer
- 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
Trial locations and contacts
7 sites in 6 countries.
7 sites in 6 countries
United Kingdom2 sites
UCL/GOSH
London
University of Newcastle Upon Tyne
Newcastle
France1 site
Imagine Institut Des Maladies Genetiques Necker Enfants Malades Fondation
Paris
Netherlands1 site
STICHTING KEMPENHAEGHE/Leiden University Medical Center
Heeze
About this study
Official title: 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.
Read the 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.
- Keywords
- Duchenne Muscular Dystrophy, Deep phenotyping, Gene therapies, Learning difficulties and autism
- Medical subject headings
- Muscular Dystrophy, Duchenne, Autistic Disorder
What is being measured
The primary outcome is the main question the study is designed to answer.
CNS Comorbidity Phenotyping
Correlate CNS comorbidity phenotypes with genotype in DMD and BMD patients
Measured: 170 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Dec 2020
- Study start11 Oct 2021
- Primary completion30 Jun 2024
- Study completion30 Jun 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Duchenne Muscular DystrophyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Enrolment
- 339 participants (actual)
Sponsor and investigators
- Lead sponsor
- Great Ormond Street Hospital for Children NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Collaborators
- Newcastle-upon-Tyne Hospitals NHS Trust, Leiden University Medical Center, Stichting Kempenhaeghe, Region Hovedstadens Apotek, Institut Necker Enfants Malades, Catholic University of the Sacred Heart, Università degli Studi di Ferrara, Universidad Complutense de Madrid
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04668716
- Sponsor's protocol ID
- 20NM35
- Status last verified
- Jul 2024
- First submitted
- 9 Dec 2020
- Last updated
- 22 Jul 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT04668716
- Acronym / sponsor ID
- 20NM35
- Keywords
- Duchenne Muscular Dystrophy, Deep phenotyping, Gene therapies, Learning difficulties and autism
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 339 participants (actual)
- Lead sponsor
- Great Ormond Street Hospital for Children NHS Foundation TrustUniversity, hospital or other
- Collaborators
- Newcastle-upon-Tyne Hospitals NHS Trust, Leiden University Medical Center, Stichting Kempenhaeghe, Region Hovedstadens Apotek, Institut Necker Enfants Malades, Catholic University of the Sacred Heart, Università degli Studi di Ferrara, Universidad Complutense de Madrid
- Study start
- 11 Oct 2021 (actual)
- Primary completion
- 30 Jun 2024 (actual)
- Study completion
- 30 Jun 2024 (actual)
- First posted
- 16 Dec 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Cross-sectional
Who may qualify
- Ages
- 5 to 50 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
- 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.
Key inclusion criteria (12 listed)
- 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)
- age 5-50 years
Key exclusion criteria (18 listed)
- 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
- any muscle disease
- a brain disorder (such as severe brain concussion in past history, congenital brain anomalies, epilepsy)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
CNS Comorbidity Phenotyping
Time frame: 170 minutes
Correlate CNS comorbidity phenotypes with genotype in DMD and BMD patients
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jul 2024.
- BIND: Brain Involvement in Dystrophinopathies study websiteLink provided by the sponsor.
Related trials for Duchenne Muscular Dystrophy
Enrolling by invitationObservational study
An Observational Study Comparing Delandistrogene Moxeparvovec (ELEVIDYS) With Standard of Care in Participants With Duchenne Muscular Dystrophy
Duchenne Muscular Dystrophy
RecruitingObservational study
Does Chronic Pain Change Over Time in Children With Duchenne Muscular Dystrophy?
Duchenne Muscular Dystrophy (DMD), Chronic Pain
RecruitingObservational study
Bone Health in Adults With Duchenne Muscular Dystrophy: A Survey on Osteoporosis, Fractures and Treatment.
Duchenne Muscular Dystrophy (DMD)
RecruitingObservational study
Development of Non-Invasive Prenatal Diagnosis for Single Gene Disorders
Invasive PreNatal Diagnosis in a Context of Family History of Single-gene Disorders, Including, Sickle Cell Disease
RecruitingPhase 1/2
PBGENE-DMD Phase 1/2a Safety and Preliminary Efficacy Study in Duchenne Muscular Dystrophy (FUNCTION-DMD)
Duchenne Muscular Dystrophy With Mutations Amenable to PBGENE-DMD
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
7 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Duchenne Muscular Dystrophy and Becker Muscular Dystrophy, run by Great Ormond Street Hospital for Children NHS Foundation Trust at 7 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United Kingdom, Denmark, France, Italy, Netherlands and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
CNS Comorbidity Phenotyping (time frame: 170 minutes). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jul 2024.