The primary objective of the second part of the study, which is the focus of this application, is to perform a comparative analysis of the cognitive profile and MRI outcomes of DMD/BMD patients.
ID
Source
Brief title
Condition
- Musculoskeletal and connective tissue disorders congenital
- Neuromuscular disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary outcome measure for this study is the measure of intelligence as
estimated by the Wechsler Intelligence test. As the sample includes
participants from a range of age groups the most appropriate version will be
used accordingly*
Secondary outcome
- Intelligence assessment:
o Raven 2 nonverbal concept formation
- Cognitive function assessments:
o Rey auditory learning task
o NEPSY-II comprehension of instruction
o NEPSY-II speeded naming
o NEPSY-II phonological processing
o NEPSY-II theory of mind (social cognition)
- Attention assessment:
o Fepsy simple reaction times
- Executive function assessment:
o BADS-C key search
- Academic attainment assessments:
o Speeded reading (WIAT-III, word reading subtest)
o Speeded arithmetic (WIAT-III, maths fluency subtest)
- MRI
o brain (sub-)volumes, cortical thickness, a voxel wise comparison of the local
distributions of grey and white matter. Possible changes in volume of specific
structures like the hippocampus or the amygdale should also follow from this
analysis.
o anatomical connectivity( mean diffusivity (MD) and fractional anisotropy
(FA).
o Resting state and task-based analysis of functional connectivity (ICA and
Seed based)
o cerebral perfusion by ASL
o Analyses of MR spectroscopy with editing for GABA
Background summary
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. Approximately 800 new cases are diagnosed annually in Europe (~80 in
the UK), with a worldwide prevalence of ~ 250,000 individuals. 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 [1-2]. 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 [3], which however have been less well defined.
Whilst improvement in the standards of care of DMD have resulted in improved
survival of these patients into adult life, the CNS comorbidities still have an
impact on the quality and participation in life for DMD and BMD patients.
Currently there is a lack of phenotypically rich information to assist in the
prognostication of CNS comorbidities, as existing databases and registries
(e.g. UK NorthStar registry) typically focus on the motor milestones and
associated physical disability of these patients. There is therefore, an urgent
need to delineate 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, as well as to pave the
way to greater biological understanding and the personalization of
interventions.
The study is divided into 2 parts, and this application refers to the second
part of the study (the first part is ongoing).
Study objective
The primary objective of the second part of the study, which is the focus of
this application, is to perform a comparative analysis of the cognitive profile
and MRI outcomes of DMD/BMD patients.
Study design
Observational case-control and cohort study
Study burden and risks
There are no invasive procedures involved in this study. There is also no
personal gain to taking part. Participants will need to come to the
investigating site in person for half a day; if they opt for MRI this may
require an additional 1.5 hour session. Travel expenses will be reimbursed and
a gift certificate of 20 euros will be given.
Gower street 0
London WC1E6BT
GB
Gower street 0
London WC1E6BT
GB
Listed location countries
Age
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)
- corticosteroid use either 10 days on/10 days off prednisolone or Vamorolone
For BMD patients:
- Male
- age 18-50 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 that eliminates
expression of Dp140 while preserving expression of Dp427 albeit at reduced
levels (assigned to BMD Group 3) or of all the isoforms (assigned to BMD Group
4).
For MRI healthy 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
- Any other severe co-morbidity or planned surgical intervention within 6
months from the study
- Inability to consent (for parents/guardians and adults) or assent. This will
exclude the rare individuals with extremely severe learning disability, as the
assent in these patients is impossible (or the consent in the adults); in
addition it will not be feasible to perform MRI in this group of patients as we
will not administer general anaesthetic. We anticipate this group will be
enriched in the genotype lacking all dystrophin isoforms, and it is because of
this that we have not indicated what is the precise number of individuals with
this genotype to be recruited.
- Non-Dutch speakers.
For MRI healthy controls:
- any muscle disease
- a brain disorder (such as severe brain concussion in past history, congenital
brain anomalies, epilepsy)
- Non-Dutch speakers
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 for 45 minutes
- not having a general practitioner
- severe learning disability which will require a general anaesthetic
Design
Recruitment
Medical products/devices used
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL79997.058.21 |